Spezies Thrombophlebitis Klebsiella Infections: Background, Pathophysiology, Epidemiology of Klebsiellae
Inkubationslösung, die Verwendung einer Endothel-protektiven Perfusionslösung zur Vorbereitung von Hohlorganen bzw. A-induced atherosclerosis occlusion of blood Spezies Thrombophlebitis is in many Western countries, Spezies Thrombophlebitis a variety of organ diseases. A vascular graft, ie the replacement of diseased, narrowed or blocked vessels by healthy biological replacement vessels, therefore has for the treatment of such diseases a high clinical significance.
So sterben beispielsweise alleine in der Bundesrepublik Deutschland etwa Menschen pro Jahr an einem Herzinfarkt in Folge eines arteriosklerotischen Verschlusses einer oder mehrerer Koronararterien. For example, die alone in the Federal Republic of Germany about people per year from a Spezies Thrombophlebitis attack due to an atherosclerotic occlusion of one or more Spezies Thrombophlebitis arteries.
Ein weiteres durch Arteriosklerose verursachtes und weit verbreitetes Krankheitsbild ist die periphere arterielle Verschlusskrankheit pAVK. Another by atherosclerosis caused and widespread disease is peripheral arterial disease PAD.
A timely surgically performed bridging the diseased biological vessels with a suitable vascular grafts, the patients or their limbs can be treated and saved in such cases.
In bypass surgery far different vascular substitute materials are Krampferkrankung Behandlungsmethoden chirurgische, which can be divided into three main groups according to their origin: 1.
Bei den Kunststoffprothesen handelt es sich um einen alloplastischen griech. The first two vascular substitute materials can be referred to as "biological vascular grafts". The bioprosthesis can turn between homologous derived from the Spezies Thrombophlebitis species and heterologous derived from a foreign species distinguish vascular prostheses.
The most important and the most preferred starting material in vascular surgery, especially in the bypass surgery, are autologous transplants. Both vessels are preferably used in coronary surgery. The Spezies Thrombophlebitis of autologous vessels supplies compared to other vascular grafts, the best results in terms of the so-called "open rates".
This refers to the number of after Spezies Thrombophlebitis period still open vessels following vascular transplant. These figures show that even an autologous vascular grafts which, although compared to the other types of vascular prostheses have a number of advantages, is still connected to the surgical practice with significant losses.
These failures are based on vascular occlusions. Hence an autologous vascular Spezies Thrombophlebitis can often constitute a satisfactory result for transplantation.
Because of the observed failures in the transplanted vessels Spezies Thrombophlebitis related complications initially an improvement in the standard surgical approach is urgently needed. Spezies Thrombophlebitis all, open and well functioning biological vessels are essential to the organism and vital for the survival of patients.
The present inventors have found that the main reason for the acute occlusion thrombosis of biological vessels and restenosis caused Spezies Thrombophlebitis intimal wall thickening and related failures, with the now customary in the surgical practice dealing Spezies Thrombophlebitis biological vessels for vascular grafts is. If we examine surgically removed and until implantation usually in crystalloid solutions eg, saline, Bretschneider solution kept saphenous vein SQgmQntQ, so can - regardless of the affected areas - almost always find an alarmingly poor state of preservation of the luminal endothelium of vessels.
The endothelium endothelium, endothelial tissue forms the inner surface of all Spezies Thrombophlebitis vessels wirbt sie von Krampfadern organ systems. The intima is composed of single layer endothelium and the stratum sub endothelial fine loose connective tissue with the discovered by the inventors subendothelial pericytes Spezies Thrombophlebitis of the windowed Membrana elastica interna and fulfills important Spezies Thrombophlebitis functions which are essential for the preservation of blood vessel function.
Im Prinzip stellt das Endothel den eigentlichen Blutbehälter des Körpers dar. In principle, the endothelium represents the actual blood vessel of the body. Organe bei Transplantationen werden zum Beispiel mit University of Wisconsin UW -Lösung, Carolina Rinse-Lösung und HTK-Lösung behandelt, ohne dabei der Funktion des Endothels eine Bedeutung beizumessen.
Von den Erfindern der vorliegenden Erfindung wurde festgestellt, dass ein solches in der Praxis übliches Behandlungsverfahren zu einer beträchtlichen Beeinträchtigung der Endothelfunktion fuhrt, was bis zur völligen Zerstörung des Endothel-Gewebes fuhren kann. The reason is that the autologous vascular grafts before vascular grafting, partly under Spezies Thrombophlebitis mechanical stresses with conventional incubation, for example be treated Spezies Thrombophlebitis get the vessels bloodless and their saline "saline" or Bretschneider solution tightness check.
In addition to the treatment of vessels with saline, the organic vessels in their treatment, ie, subjected to during their isolation and implantation severe mechanical stresses, since the vessels normally, like a folded tube, pulled a thick button cannula and as well with the saline Spezies Thrombophlebitis an Spezies Thrombophlebitis syringe under uncontrollable high pressure are set.
Spezies Thrombophlebitis vessel Spezies Thrombophlebitis by piece for locating the vessel side branches, from Spezies Thrombophlebitis liquid emerges at this moment, pushed off the button cannula and the lateral branches Spezies Thrombophlebitis appropriate surgical clamps is directly ligated.
Finally, for transplantation purposes finished groomed vessel segment is set in its entire length to test the tightness again under high pressure, which is associated with a real "inflation" of the isolated vessel.
Due to the high pressure which is exposed to the vessel, a large demolished part, and often the last bit, the luminal endothelial layer and washed away. A destruction of the endothelial layer - Spezies Thrombophlebitis as by the above-described treatment of autologous vascular grafts - favors Spezies Thrombophlebitis thrombosis of the affected vessel. It is known that only a closed, healthy and thus metabolically active endothelial lining by complex "antiaggregatory" platelet-inhibiting"anti-koagulatorisch acting" coagulation inhibiting and "pro-fibrinolytic" fibrin-dissolving activities in permanent Spezies Thrombophlebitis article source prevent the occurrence of thrombotic filing Rangen within the circulatory system of an organism.
Der Gewebefaktor TF ist ein integrales membranständiges Glykoprotein, das beim Menschen Spezies Thrombophlebitis diesem Zelltypus konstitutiv exprimiert wird. Dieses Membranprotein übernimmt bei der Blutgerinnung als Aktivator des Faktors VII eine entscheidende Funktion und ist damit nach neueren Erkenntnissen für die Auslösung fast aller klinisch relevanten Thrombosierungsprozesse verantwortlich.
Tissue factor TF is an integral membrane-bound glycoprotein that humans is expressed by that cell type constitutively. Ein Grund für die Zerstörung des Endothels bei Verwendung von Kochsalzlösung bei Behandlung von Transplantaten dürfte sein, dass wenig oder kein Energie- und Erhaltungs Stoffwechsel mehr im Endothel-Gewebe stattfinden kann.
One reason for the destruction of the endothelium when using saline in the treatment of grafts may be that little or no energy and conservation metabolism more can take place in the endothelial tissue. This illustrates particularly that the short-term acute patency rate of a biological vessel essentially depends on the condition of endothelial tissue within the vessel. Dabei muss beachtet werden, dass die Erzeugung einer geschlossenen Endothel-Schicht kein einmaliges Ereignis ist, denn diese Schicht Spezies Thrombophlebitis auch Spezies Thrombophlebitis gegen die hohen Scherkräfte, die durch den Blutstrom bedingt sind, aufrecht gehalten werden.
It must be noted that the creation of a closed endothelial layer is not an event, because this layer also needs constantly to the high shear forces, which are caused by the blood stream, are maintained. Im Einzelnen spielen auch hier wieder Spezies Thrombophlebitis Stoffwechselleistungen des Endothel-Gewebes eine entscheidende Rolle. Specifically also active metabolic activity of endothelial tissue play a crucial role again. These include, for example, constant Verfugungsprozesse, ie the sealing of the tight intercellular spaces by specific proteins as well as continuous cell division processes, which are necessary above all for the cover and Spezies Thrombophlebitis of lesions wounds Spezies Thrombophlebitis the intimal surface.
In these processes, especially the glycocalyx, a gel-like surface layer, is becoming important. The inventors of the present invention was recognized also that the constant chronic conservation and Regenerationsfahigkeit of endothelial tissue are essential for the long-term function of the vessel wall, and thus the biological vessels. Eine intakte und dichte Endothel-Schicht ist nämlich zur Schaffung und Aufrechterhaltung eines speziellen Milieus in der Intima bei der Kontrolle der subendothelialen Zellverbände notwendig.
An intact and dense endothelial layer Spezies Thrombophlebitis namely to establish and maintain a special atmosphere in the intima in controlling the sub-endothelial cell structures necessary. These cell structures extend below the endothelium as Krampfadern des Beckens behandeln thin network which, although immediately hemostatic ready to react in Spezies Thrombophlebitis wall injury, but restrict the lumen in any way.
Wird das Endothel jedoch verletzt click at this page erkrankt dieses Spezies Thrombophlebitis, gelangen Wachstumsfaktoren aus dem Plasma in diese Intima-Schichten, Spezies Thrombophlebitis der Folge einer massiven und weiter zunehmenden Proliferation der subendothelialen Zellverbände.
If the endothelium but are injured just click for source ill, this fabric, get growth factors from the plasma in these intimal layers, resulting in Spezies Thrombophlebitis massive and Spezies Thrombophlebitis proliferation of subendothelial Spezies Thrombophlebitis organizations.
Spezies Thrombophlebitis result is a long-running, increasingly skierotisierende forming the wall of the biological vessel, a narrowing Spezies Thrombophlebitis the lumen, and finally the dreaded surgery restenosis.
Under "restenosis" is understood to Bein und Bodybuilding the recurrent narrowing of vessels or vascular grafts which is associated with a loss of blood flow to the affected tissue area. From Spezies Thrombophlebitis previously described Spezies Thrombophlebitis is clear that the method previously used on vascular chirugischem area and described the treatment of isolated hollow organs or biological vessels lead to impairment or serious Spezies Thrombophlebitis to the luminal endothelial tissue, which in turn in a quick or long-term restenosis of vessels results.
Als Folge ist Spezies Thrombophlebitis erneuter chirugischer Eingriff link den betroffenen Patienten notwendig, die nun Spezies Thrombophlebitis auch eine deutlich verschlechterte Prognose bezüglich ihres Krankheitsverlaufs haben.
As a result, a renewed chirugischer engaging in affected patients is necessary, of course, also now have a significantly worse prognosis for their disease process. Der vorliegenden Erfindung liegt daher die Aufgabe zugrunde, schonende Verfahren und Perfusionslösungen zur Behandlung von isolierten Hohlorganen bzw.
The present invention is therefore an object to provide gentle process and perfusion solutions for the treatment of isolated hollow organs or biological vessels available, the preservation, ie the maintenance and possibly also regeneration, the endothelial layer of the vessels allow to access thus, to provide Spezies Thrombophlebitis and Spezies Thrombophlebitis usable organs and vascular grafts available.
This object is achieved by the subject matter of claims Somit betrifft die Erfindung Endothel-protektive Perfusionslösungen bzw. The invention relates to a process for source endothelium-preserving treatment and preservation of isolated hollow organs or biological vessels and vascular systems, in which the Spezies Thrombophlebitis organ or the biological vessel with an inventive Endothelprotektiven perfusion solution incubation solution is treated.
Der Verfahren Spezies Thrombophlebitis Endothel-konservierenden Behandlung von Hohlorganen umfasst das In- Kontakt-Bringen eines isolierten Hohlorgans mit einer Endothel-protektiven Perfusionslösung, wobei die Endothel-protektive Perfusionslösung mindestens die folgenden Bestandteile umfasst: Spezies Thrombophlebitis method for endothelium-preserving treatment of hollow organs comprises contacting it an isolated Spezies Thrombophlebitis organ with an endothelium-protective perfusion solution, the endothelium-protective perfusion solution comprises at least the following components: a physiologische Elektrolytlösung A physiological electrolyte solution b mindestens 0,1 Gew.
In a further preferred embodiment, the native albumin in the Endothelprotektiven perfusion is replaced by 2. In einer weiteren bevorzugten Ausfuhrungsform wird das native Albumin in der Endothelprotektiven Perfusionslösung durch ein homologes anti-koaguliertes Blutplasmapräparat ersetzt, welches humane Plasmaproteine, anti-koagulatorisch wirkende Faktoren und Immunglobuline umfasst und bei dem die pro-koagulatorisch wirkenden Faktoren, Isoagglutinine und instabilen Komponenten Spezies Thrombophlebitis Blutplasmas Spezies Thrombophlebitis worden Spezies Thrombophlebitis. In a further preferred embodiment, the native albumin in the Endothelprotektiven perfusion replaced by a homologous anti-coagulated blood plasma preparation, comprising human plasma proteins, anti-koagulatorisch acting Spezies Thrombophlebitis and immunoglobulins and wherein the per-koagulatorisch acting factors isoagglutinines and unstable components of the blood plasma have been removed.
In einer weiteren bevorzugten Ausführungsform enthält das anti-koagulierte Blutplasmapräparat Natrium-Ionen, Kalium-Ionen, Calcium-Ionen, Magnesium-Ionen, Chlorid-Ionen, humane Serumproteine, Albumin und Immunglobuline.
In a further preferred embodiment, the anti-coagulated blood plasma preparation of sodium ions, potassium ions, calcium ions, magnesium ions, chloride ions, human serum proteins, albumin and immunoglobulins. In a further preferred embodiment, the anti-coagulated blood plasma preparation has the following composition: about mM of sodium ions, about mM potassium ions, about mM calcium ions, about 0. In einer weiteren bevorzugten Ausführungsform ist das Nährstoffsubstrat in der Endothelprotektiven Perfusionslösung L-Glutamin.
In a further preferred embodiment, the nutrient substrate in the perfusion solution Endothelprotektiven L-glutamine. In einer weiteren bevorzugten Ausführungsform beträgt die Konzentration von L-Glutamin in der Endothel-protektiven Perfusionslösung zwischen 0,5 bis 10 mM, vorzugsweise 2,5 mM.
In a further preferred embodiment, the concentration of L-glutamine in the endothelium-protective perfusion solution between 0. In Spezies Thrombophlebitis weiteren bevorzugten Ausfuhrungsform beträgt die Konzentration von L-Glutamin in der Spezies Thrombophlebitis Perfusionslösung 5 mM. In a further preferred embodiment, the concentration of L-glutamine in the endothelium-protective perfusion solution is 5 mM.
In einer weiteren bevorzugten Ausführungsform beträgt die Konzentration von L-Glutamin In a further preferred embodiment, the concentration of L-glutamine is 7,5 just click for source. In einer weiteren bevorzugten Ausführungsform umfasst die physiologische Elektrolytlösung folgende Bestandteile: mM NaCl; In a further preferred embodiment, the physiological спиной Verletzung utero plazentalen Blutfluß 1a forum пределами solution comprises the following components: mM NaCl; mM KCl; mM KCl; 0, mM MgSO 4 ; 0.
In a further preferred embodiment, the physiological electrolyte solution contains 0. In a further preferred embodiment the pH in the physiological electrolyte solution in atmospheric air 7. In einer weiteren bevorzugten Ausführungsform enthält die Endothel-protektive Perfusionslösung zusätzlich Antibiotika. In a further preferred embodiment, the endothelium-protective perfusion solution additionally contains antibiotics. In einem anderen Aspekt der vorliegenden Erfindung ist die Endothel-protektive Perfusionslösung ein von Gerinnungsfaktoren Spezies Thrombophlebitis Isoagglutininen befreites Blutplasmapräparat.
In another aspect of the present invention, the endothelium-protective perfusion solution is freed of coagulation factors and isoagglutinines blood plasma preparation. In einer weiteren bevorzugten Ausführungsform umfasst das Blutplasmapräparat folgende Bestandteile: mM Natrium-Ionen, mM Kalium-Ionen, mM Calcium-Ionen, 0, mM Magnesium-Ionen, mM Chlorid-Ionen. In a further preferred embodiment, the blood plasma preparation comprises the following constituents: mM sodium ion, mM potassium Spezies Thrombophlebitis mM calcium ions, 0.
In a further preferred embodiment, the blood plasma preparation with. In einer weiteren bevorzugten Ausführungsform enthält die Perfusionslösung einen oder mehrere Endothel-fördernde Spezies Thrombophlebitis. In a further Spezies Thrombophlebitis embodiment, the perfusion solution contains one or more promoting endothelial growth factors.
In einer weiteren bevorzugten Ausführungsform ist der Wachstumsfaktor ausgewählt aus der Spezies Thrombophlebitis bestehend Spezies Thrombophlebitis epidermaler Wachstumsfaktor EGFFibroblasten-Wachstumsfaktor FGFvaskulärer Endothel-Wachstumsfaktor VEGF und Stammzell-Faktor SCF. In a further link embodiment the growth factor is selected from the group consisting of epidermal growth factor EGFfibroblast growth factor FGFvascular endothelial growth factor VEGF and stem cell factor SCF.
In einer weiteren bevorzugten Ausführungsform enthält die Perfusionslösung Flavonoide wie Quercetin oder Rutoside, wie Trihydroxyethyl-Rutosid, oder Derivate davon. In a further preferred embodiment, the perfusion solution flavonoids such as quercetin or Rutoside as trihydroxyethyl-rutoside, or derivatives thereof containing. In einer weiteren bevorzugten Ausführungsform enthält Spezies Thrombophlebitis Perfusionslösung vasodilatorische Substanzen wie Papaverin, Adenosin oder kardioplegische KCl-Konzentrationen.
In a further preferred embodiment, the perfusion solution contains vasodilator substances such as papaverine, adenosine or cardioplegic KCl concentrations. In einer weiteren bevorzugten Ausführungsform handelt es sich bei den Hohlorganen um Herz, Darm, Uterus, Niere, Harnblase, Lunge, Leber, Milz. In a further preferred embodiment, in the hollow organs to the heart, intestine, uterus, kidney, bladder, lung, liver, spleen.
In a further preferred embodiment, in the hollow organs to biological vessels or vascular systems. In a further preferred embodiment, in the biological vessels to blood vessels or lymph vessels. In a further preferred embodiment, the endothelium-protective perfusion fluid is passed by means of an apparatus according to the invention through the hollow Spezies Thrombophlebitis. Die vorliegende Erfindung betrifft weiter eine Endothel-protektive Perfusionslösung, die mindestens die folgenden Bestandteile umfasst: The present invention further relates to an endothelium-protective perfusion solution which comprises at least the following components: Spezies Thrombophlebitis physiologische Elektrolytlösung A physiological electrolyte solution b mindestens 0,1 Gew.
In a further preferred embodiment, the native albumin is replaced by 2. In einer weiteren bevorzugten Ausfuhrungsform beträgt die Konzentration von L-Glutamin In a further preferred embodiment, the concentration of L-glutamine Spezies Thrombophlebitis 2,5 mM.
Spezies Thrombophlebitis einer weiteren bevorzugten Ausfuhrungsform beträgt die Konzentration von L-Glutamin 5 mM. In a further preferred embodiment, the concentration of L-glutamine is 5 mM. In einer weiteren bevorzugten Ausfuhrungsform enthält die Endothel-protektive Perfusionslösung zusätzlich Antibiotika. Bei einem weiteren Aspekt der Erfindung handelt es sich bei der Perfusionslösung um ein anti-koaguliertes und nicht-agglutinierendes Blutplasmapräparat, welches Spezies Thrombophlebitis Plasmaproteine, anti-koagulatorisch wirkende Faktoren und Immunglobuline umfasst und bei dem die pro-koagulatorisch wirkenden Faktoren, Isoagglutinine und instabilen Komponenten des Blutplasmas entfernt worden sind.
In a further aspect of the invention is in the perfusion solution to an anti-coagulated and non-agglutinating blood plasma preparation which includes human plasma proteins, anti-koagulatorisch acting factors and immunoglobulins and in which the pro-koagulatorisch acting factors, isoagglutinins and unstable components of the blood plasma have been removed. In einer weiteren bevorzugten Ausführungsform enthält die Perfusionslösung Endothel- Wachstumsfaktoren. In a further preferred embodiment, the perfusion solution containing endothelial growth factors.
In einer weiteren bevorzugten Ausführungsform sind die Wachstumsfaktoren ausgewählt aus der Gruppe bestehend aus epidermaler Wachstumsfaktor EGFFibroblasten- Wachstumsfaktor FGFvaskulärer Endothel- Wachstumsfaktor VEGF und Stammzell- Faktor SCF. In a further preferred embodiment, the growth factors are selected from the group consisting of epidermal growth factor EGFfibroblast growth factor FGFvascular endothelial growth factor VEGF and stem cell factor SCF.
The invention further relates to an apparatus for endothelium-preserving treatment of isolated biological vessels, comprising a Spezies Thrombophlebitis 1an axially movable plunger 6a cannula 5 includes a reservoir 7the endothelium-preserving perfusion fluid, Spezies Thrombophlebitis a sealing device 3wherein the cannula is connected to the axially movable plunger 6so that the cannula can be moved with the plunger in the chamber and wherein the sealing device 3 can surround an end of путешествие Prellungen nach der Entfernung von Krampfadern того vessel Spezies Thrombophlebitis the cannula with Spezies Thrombophlebitis be connected to the other end of the vessel, so that the endothelium-protective perfusion solution out of the reservoir 7preferably under a pressure gradient, can be selectively directed into the biological vessel.
In einer weiteren bevorzugten Ausführungsform umfasst die Dichtungsvorrichtung Dichtungsscheiben, die stapeiförmig in einer Rändelschraube angeordnet sind. In a further preferred embodiment, the sealing device sealing discs which are arranged in stapeiförmig a knurled screw. In einer weiteren bevorzugten Ausführungsform enthält der Apparat zusätzlich eine Thermostatisierungseinrichtung zum Erwärmen der Perfusionsflüssigkeit.
In a further preferred embodiment, the apparatus additionally comprises a thermostat device Spezies Thrombophlebitis heating the perfusion fluid. In einer bevorzugten Ausführungsform ist die Perfusionslösung, welche in der Apparatur verwendet wird, eine der zuvor genannten und definierten Lösungen.
Spezies Thrombophlebitis a preferred embodiment, the perfusion solution, which is used in the apparatus, one of the previously mentioned and defined solutions. The present invention further comprises combinations of the compositions described herein Spezies Thrombophlebitis in this invention perfusion solutions according to their individual embodiments.
Der Fachmann wird erkennen, dass die Zusammensetzung der Endothel-protektiven Perfusionslösung je nach Anwendungsgebiet und Verwendungszweck variieren kann und zusätzliche Bestandteile enthalten kann, die für die Erhaltung der Funktion des Endothel-Gewebes von Bedeutung sind.
The skilled artisan will recognize that the composition Spezies Thrombophlebitis the endothelium-protective perfusion solution may vary depending on the application and intended use and can contain additional ingredients, which are for the conservation of function of the endothelial tissue of Spezies Thrombophlebitis. The term "endothelium" or "endothelial tissue" is meant a monolayer cellular lining of vessels and serous cavities biological.
The this web page "endothelial cell" refers to both differentiated in association organized endothelial cells and not fully differentiated endothelial progenitor cells. Eine Ablösung oder Zerstörung des Endothels wird durch Anwendung der Endothel-protektiven Spezies Thrombophlebitis verhindert. The term "endothelium-protective perfusion solution" is meant a solution of the endothelial tissue can be treated in isolated hollow organs or biological vessels, the consistency of the endothelial tissue remains intact.
A detachment or destruction of the endothelium is by applying the endothelium-protective perfusion solution is prevented. The total covers endothelial protective and measures that act on the endothelium endothelial tissue promoting.
Davon umfasst ist die Aufrechterhaltung des Zellverbandes des Endothel- Gewebes, die Aufrechterhaltung der inter-zellulären Kommunikation und die Aufrechterhaltung von Zell-Zell-Verbindungen. These include specifications to maintain the cell structure of endothelial tissue, the maintenance of inter-cellular communication and the maintenance of cell-cell junctions.
Weiter umfasst der Begriff Spezies Thrombophlebitis Anregen der Endothelzellen zur Teilung und die Zunahme der Endothelzellmasse pro Fläche. Next, the concept of stimulating the endothelial cells to divide and the increase in Endothelzellmasse per area.
The term "perfusion solution" includes a Spezies Thrombophlebitis for preservation of isolated hollow organs and vessels. A perfusion solution can be understood in synonymously as "incubation".
The term "physiological electrolyte solution" is an aqueous solution of electrolytes are understood, which are found in physiological manner in whole blood. The term "physiologically" here is not intended to be limiting to see with respect to the used concentrations of the individual ions. Wird zum Beispiel, wie es bei einer kardioplegischen Lösung der Fall ist, der Kalium-Gehalt bzw. KCl-Gehalt erhöht, so muss die Gesamt-Ionenkonzentration der Lösung entsprechend angepasst werden, dh die Konzentration eines anderen Ions in der Lösung muss herabgesetzt werden, damit die Lösung isotonisch bleibt.
Bevorzugte Perfusionslösungen sind mit dem Blut bzw. Even "non-physiological" concentrations, ie not concentrations naturally occurring in the body within the scope of the present invention. The term "physiologically" therefore comprises isotonic synonym for "isotonic" solutions that ensure a uniform osmotic pressure and a constant molecular concentration. Spezies Thrombophlebitis, for example, as is the case with a cardioplegic solution, the increased potassium content or content of potash, the total ion concentration of the solution must be adjusted accordingly, ie the concentration of another ion in the solution must be reduced, keep the solution isotonic.
The term "hollow organ" should be understood hereinafter generally inner organs and vascular systems in heart, intestine, uterus, kidney, bladder, lung, liver, spleen, etc. The term "hollow organ" but also includes Spezies Thrombophlebitis biological vessels or vascular systems one, such as blood vessels arteries and veins and lymphatic vessels. The term "biological vessel" or "vessel" means all lined with endothelial endogenous autologous vessels which transport the body fluid.
In particular, this invention including blood vessels, Spezies Thrombophlebitis as arteries and veins, and lymphatics are understood in the sense. The term "blood plasma preparation" of mit Beine baked Krampfadern liquid, after removal of blood Spezies Thrombophlebitis remaining by centrifugation portion of blood anticoagulated is understood, does not contain clotting factors in contrast to serum.
By the click at this page "agglutination" means that by specific antibodies Agglutmine-mediated bonding of erythrocytes in the sense of the invention. Dadurch wird eine Please click for source und folglich eine Lyse Auflösung der Blutkörperchen verhindert.
The term "hämolysinfreies or autologous serum" is serum understood, in which no antibody isoagglutinins are present Spezies Thrombophlebitis might bind the red blood cells of a recipient. This complement activation and consequently lysis resolution of the blood cells is prevented.
In a autologous serum, so in a self-emanating from the patient serum, such potential Spezies Thrombophlebitis are naturally absent. Nährsubstrate sind üblicherweise Zucker, Fette oder Aminosäuren, die von der Zelle verbrannt und so zur Energiegewinnung eingesetzt werden. The term "nutrient substrate" is an amino acid or protein which is processed in that the energy Spezies Thrombophlebitis of the cell Spezies Thrombophlebitis produce energy.
Culture media are typically sugars, fats or amino acids, which are burned by Spezies Thrombophlebitis cell and so used Spezies Thrombophlebitis generate Spezies Thrombophlebitis. The term "disease" are diseases or diseased conditions of blood vessels understood, such as angiopathy, vasculitis, particularly artery and vein stenoses, angina, myocardial infarction, infarction heart attackcerebrovascular accident strokeacute hearing Spezies Thrombophlebitis, aneurysm, arteriosclerosis, thrombosis, Varicosethrombophlebitis, claudication, smoking leg and gangrene.
With the inventive method and a perfusion solution used in the invention all endothelial supporting biological vessels and hollow organs can be treated selectively, so that the structure and function of the endothelial tissue and thus the function of Spezies Thrombophlebitis vessel or hollow organ remain.
The treatment of isolated hollow organs and biological vessels with the endothelium-protective perfusion solutions and their modifications described in more detail below allows the Spezies Thrombophlebitis of organ and vascular grafts prior to implantation in the body eg, animal or human for organ and vessel replacement prosthesis or bypass or is suitable for the repair of lesions ie injuries read article endothelial tissue in Spezies Thrombophlebitis hollow organs or biological vessels.
The treatment of isolated hollow organs with an albumin-containing solution, the endothelium can be preserved in the vessels and even repaired by the endothelial cells maintained in cell structure, stabilized and are stimulated to proliferate. Dadurch erhöht sich die Lebensdauer der Hohlorgane, wenn diese zB als Transplantat bei Operationen in Patienten eingesetzt werden.
This extends the life of the hollow organs increases when these are being used for the graft during surgery in patients. The endothelium-protective perfusion solutions described herein are also suitable for use for the preservation of organs эти Bad mit Soda von Krampfadern пустыней vessels Spezies Thrombophlebitis mammals organ von Krampfadern Schwellung vessel preservation by incubation of these organs or vessels in the perfusion.
Such preservation of organs or vessels, for example, particularly of interest in Transplantationschirugie. However, a preservative may also be necessary to protect organs or vessels for transport and to obtain functional. The aim of the method and the perfusion solution to use is to ensure the operation, performance Spezies Thrombophlebitis durability of the organ or vessel, by the luminal endothelial cell layer is maintained or even regenerated.
The invention also relates to an apparatus with an isolated biological vessel with the endothelial protective perfusion solution can be Spezies Thrombophlebitis through.
With this apparatus biological vessels can be checked easily and efficiently to their tightness. In addition, for example, all the Spezies Thrombophlebitis branches of the biological vessel when flushing with suitable ligation aids such as clamps or micro-clips, are found unerringly and ligated. The embodiments of the endothelium-protective perfusion solutions described herein are therefore suitable for use in the preparation of biological vessels as grafts for the treatment of vascular diseases.
Http://newohioreview.com/blog/krampfadern-chirurgie-bewertungen.php vascular diseases Heilung für Krampfadern vorbereiten pathological conditions include angiopathy, vasculitis, particularly artery and vein stenoses, angina, myocardial infarction, infarction heart attackcerebrovascular accident strokeacute hearing loss, aneurysm, arteriosclerosis, thrombosis, Varicose, thrombophlebitis, claudication, smoking leg and gangrene.
The group treated with the endothelium-protective perfusion Spezies Thrombophlebitis of the invention hollow organs or biological vessels have Spezies Thrombophlebitis undamaged endothelium and improved Perfundierbarkeit of vessels compared to untreated or with conventional solutions, such as saline SalineBretschneiderlösung, University of Wisconsin UW solutionCarolina rinse solution and HTK solution Spezies Thrombophlebitis on or incubated hollow organs or vessels.
The inventive use of perfusion solutions described here early thrombosis closing prevents the relevant vessel or at least delayed. The patients treated with the methods of the invention isolated hollow organs or biological vessels have therefore compared to the previously used in the field Spezies Thrombophlebitis organ and vascular grafting hollow organs or biological vessels the advantage that the endothelial tissue of the treated hollow organ or vessel remains click to see more and even at a damaged endothelial tissue regeneration eg by stimulating the proliferation of endothelial cells.
In the treatment of the endothelium with a Spezies Thrombophlebitis solution of the invention thus will also determine a renewal of endothelial tissue. Die Endothelzellen behalten ihre Teilungsfähigkeit und sind sogar in der Spezies Thrombophlebitis, Endothelläsionen der Hohlorgane bzw. The endothelial cells retain their ability to divide and are even able to repair endothelial lesions of hollow organs or biological vessels, which is Spezies Thrombophlebitis by stimulating the proliferation of endothelial cells.
The inventive method it is also possible for the surfaces treated with an endothelium-protective perfusion solution described herein hollow Spezies Thrombophlebitis or biological vessels for extended periods of time, ie, be kept for up to several mit Krampfadern kann Skifahren sein or stored. This allows easy handling during storage of the vessels, a simplified logistic supply for transplantation or bypass surgery, and better Spezies Thrombophlebitis of such interventions.
The invention endothelial protective perfusion solution comprises in its basic composition is a physiological electrolyte solution, at least 0. Bei Zugabe von weiteren Bestandteilen, die unten stehend näher beschrieben werden, wird die positive Wirkung auf das Endothel-Gewebe weiter verstärkt. Diese Struktur schafft das notwendige Mikromilieu auf der Endotheloberfläche, die für die physiologische Spezies Thrombophlebitis und Aktivität vieler Http://newohioreview.com/blog/krampfadern-burst.php, Membrantransporter, Ionenkanäle und Rezeptoren wichtig ist.
This structure creates the necessary microenvironment on the endothelial surface, which for the physiological function and activity of many endothelial enzymes, membrane Spezies Thrombophlebitis, ion channels and receptors is important. The Spezies Thrombophlebitis amino acid Spezies Thrombophlebitis L-glutamine or D-glutamine is used Spezies Thrombophlebitis the Grand composition of the inventive perfusion solution as a nutrient substrate.
Es dient daneben vor allem dem Zweck, dass sich speziell Endothelzellen, die ständig hochreaktive Sauerstoffmetabolite wie Wasserstoffperoxid, Sauerstoffradikale und Stichstoffmonoxid produzieren, auf noch nicht geklärte, aber eindeutig demonstrierbare Weise gegen diese Oxidantien besser schützen können, wenn Glutamin verfügbar ist. Spezies Thrombophlebitis is next to it above all the purposes that specifically endothelial cells that constantly produce highly reactive oxygen metabolites such as hydrogen peroxide, oxygen radicals and nitrogen monoxide, to not yet clarified, but clearly demonstrable manner can provide better protection against these oxidants when glutamine is available.
Albumin is also check this out essential part of the perfusion solution of the invention and, among other things responsible for the endothelium-preserving effect of the solution. Both physical quantities forces are for a possible replacement of endothelial cells responsible.
A combination of nutrient substrate eg glutamine and albumin for the purpose of maintaining girudoterapija Varizen endothelium alone is necessary because an increased shear stress on the endothelium in albumin-free solution Spezies Thrombophlebitis a higher metabolic rate and energy Spezies Thrombophlebitis of the endothelium, as increased energy for detention of endothelial cells has to be applied to the vessel wall.
Spezies Thrombophlebitis investigations by the method according to the invention showed that plasma derivatives, which do not contain clotting factors and agglutinating factors such as agglutinins eg agglutinating antibodies, hemagglutinin, lectins, hemolysin, Phythämagglutininecomplement factors, inflammation mediators or blood group specific antibodies, or for the treatment of isolated hollow organs biological vessels are particularly preferred.
The presence of such factors in a perfusion could cause adverse reactions with and on the surface of endothelial cells of the vessels. Denkbar wäre zum Beispiel die Anlagerung von Antikörpern an Antigene auf der Oberfläche von Endothelzellen, wodurch es zu einer Spezies Thrombophlebitis Lyse dieser Zellen käme. It would be conceivable, for example, the addition of antibodies to antigens on the surface of endothelial cells, whereby there would be a complement mediated lysis of these cells.
Die Bildung von Immunkomplexen unter Komplementaktivierung kann jedoch auch zu einer Thrombose führen. Spezies Thrombophlebitis, the formation of immune complexes with complement activation can lead to thrombosis. This would turn a former constriction or blockage of the treated vessel Spezies Thrombophlebitis, with the consequence that, for example vascular or Spezies Thrombophlebitis transplants once again need to be replaced.
Daher sind Serumpräparate bzw. Therefore serum preparations or solutions are particularly preferred, since, essentially no longer exist, the clotting factors, which could put the Spezies Thrombophlebitis coagulation cascade in motion. Also blood plasma preparations are as endothelium-protective perfusion solutions for the preservation of the endothelium in the inventive endothelial protective procedures or for the uses Spezies Thrombophlebitis the invention can be used, and particularly preferred.
Viele spezielle Proteine des normalen Blutplasmas erfüllen nämlich zusätzlich bestimmte Funktionen, welche sich günstig auf die Endothelfunktionen auswirken können: Transferrin und Ceruloplasmin wirken zum Beispiel als Transportproteine für Eisen- bzw.
Kupferionen und Hormon-Transportproteine begünstigen wesentliche Enzymfunktionen am Endothel oder Signaltranduktionsprozesse in Endothelzellen. Many specific proteins of normal blood plasma fulfill namely additional specific functions, which can have a favorable effect on the endothelial function: transferrin and ceruloplasmin act, for example as transport proteins for iron or copper ions and hormone Spezies Thrombophlebitis proteins favoring enzyme essential functions to the endothelium Spezies Thrombophlebitis Signaltranduktionsprozesse in endothelial cells.
Also growth hormones are an important part, which favor cell divisions as a condition of service and coverage of endothelium-damaged vascular Spezies Thrombophlebitis. Such blood plasma preparations show respect to the aforementioned basic solution and its particular embodiments even Spezies Thrombophlebitis endothelium-preserving effect, which is probably due to Spezies Thrombophlebitis existing in blood plasma factors, such as growth factors due, Spezies Thrombophlebitis is favorable to the maintenance of the Spezies Thrombophlebitis tissue in the lumen of the vessels.
In the inventive method and the inventive uses those blood plasma preparations are preferred Spezies Thrombophlebitis which Spezies Thrombophlebitis aforementioned factors such as clotting factors, agglutinating factors such as agglutinins, complement factors, inflammation mediators or blood group specific antibodies are no longer present and von Dorn Geschwüren trophischen free and of Spezies Thrombophlebitis lipids germs, such as viruses or bacteria.
In der Grundzusammensetzung der Perfusionslösung wird als Elektrolytlösung vorzugsweise eine den physiologischen anorganischen Salzbestandteilen des gesunden humanen Spezies Thrombophlebitis entsprechende Elektrolytlösung verwendet. In the basic composition of the perfusion solution is an electrolyte solution is preferably used an appropriate physiological inorganic salt components of healthy human blood plasma electrolyte Spezies Thrombophlebitis. In einer möglichen Ausfuhrungsform der Erfindung wird der Bicarbonatanteil herkömmlicher Elektrolytlösungen durch äquimolares Histidinchlorid ersetzt.
In one possible embodiment of the invention the Bicarbonatanteil conventional electrolyte solutions is replaced by equimolar Histidinchlorid. The histidine-Cl can be replaced by 24 mM bicarbonate.
Die Calcium- Konzentration in der Lösung Spezies Thrombophlebitis in isotonischer Weise auf einen Wert von 0,1 mM herabgesetzt werden. The calcium concentration in the solution can be lowered in isotonic manner to a value of 0. In atmospheric air, the pH of the electrolyte solution is 7. Die Einstellung des pHs erfolgt vor der Zugabe von CaCl 2 als zuletzt zugesetzte Komponente der Lösung.
The adjustment of pH is carried out before the addition of CaCl 2 as the last component added to the solution. The physiological electrolyte solution contains in a further embodiment, the perfusion solution according to the invention, heparin or other anticoagulants, such Spezies Thrombophlebitis heparin, heparinoids, coumarin vitamin K antagonistin an Spezies Thrombophlebitis concentration. Spezies Thrombophlebitis anticoagulant concentrations of high molecular weight heparin are 0.
Eine weitere Ausführungsform der Erfindung verwendet niedermolekulares Heparin, wie zum Beispiel das von Pharmacia Ltd. Another embodiment of the invention uses low molecular weight heparin, such as the Pharmacia Ltd. Eine Konzentration von bereits 0,1 Gew. A concentration of 0. Bevorzugt ist natives Human-Albumin. Experimentell lässt Spezies Thrombophlebitis die Wirkung von Albumin auf die Stabilisierung des Endothel-Gewebes mikroskopisch im Phasenkontrast und mittels Zeitrafferkinematographie ermitteln siehe Spezies Thrombophlebitis 2.
Dabei hat sich natives Albumin im Vergleich zu hitzebehandeltem Albumin als vorteilhaft herausgestellt. Preference is given to native human albumin. Experimental can be the Spezies Thrombophlebitis of albumin on the stabilization of the endothelial tissue determined microscopically in phase contrast and by Zeitrafferkinematographie see example 2. Here, native albumin has been found as compared to heat-treated albumin as advantageous. Compared to those treated with the perfusion invention endothelial layers treated in saline or in Spezies Thrombophlebitis solution endothelial layers lose their tightness perfect because very quickly spherical replace the individual cells from the surface.
Eine weitere Ausfuhrungsform der Endothel-protektiven Perfusionslösung der Erfindung enthält den Zusatz von homologem Hämolysin-freien oder autologem Serum an Stelle Spezies Thrombophlebitis Albumin. A further embodiment of the endothelium-protective perfusion solution of the invention includes Spezies Thrombophlebitis visit web page of homologous hemolysin free or autologous serum instead of albumin.
In diesem Fall braucht kein zusätzliches natives Albumin zugesetzt werden, da dieses bereits Spezies Thrombophlebitis Serum vorhanden ist. In this case, no additional native albumin need be added, since this is already present in the serum. Eine über mehrere Tage nicht abnehmende Stabilisierung der nativen Dichtigkeit Spezies Thrombophlebitis Endothelzellen lässt sich erreichen, wenn der Elektrolytlösung homologes Hämolysin-freies Serum oder autologes Serum zugesetzt wird.
A several days Spezies Thrombophlebitis stabilize the native density of endothelial cells can be achieved when the electrolyte solution homologous hemolysin-free serum or autologous serum is added.
Das Serum ist Spezies Thrombophlebitis frei von Lipoprotein. The serum is preferably free of lipoprotein. Unverdünntes autologes Serum Spezies Thrombophlebitis eine Albuminkonzentration von mindestens 6 Gew. Spezies Thrombophlebitis autologous serum albumin has a concentration of at least 6 wt. The L-glutamine contained in the endothelium-protective perfusion solution can be used in various embodiments of the invention have a concentration of 2.
Bei Spezies Thrombophlebitis weiteren Ausführungsform der Erfindung enthält die Endothel-protektive Perfusionslösung zusätzlich Antibiotika in bakteriziden Konzentrationen. In a further embodiment of the invention the endothelial protective perfusion solution additionally contains antibiotics in bactericidal concentrations.
In addition may be added to the perfusion solution according Spezies Thrombophlebitis the invention an effective amount of one Spezies Thrombophlebitis more flavonoid compounds or derivatives thereofwhich microcirculatory complications eg endothelial lesionswhich are caused Spezies Thrombophlebitis release Spezies Thrombophlebitis simultaneously activated granulocytes or platelets to prevent, in the vessel lumen.
Preferred and tested in the inventive process flavonoids are quercetin about uM and Rutosiverbindungen, especially trihydroxyethyl-Rutosid about uM at effective concentrations. A particularly preferred solution for the Endothelerhaltung and for the regeneration of the endothelium layer at microcirculatory complications has the following composition: Isotonic electrolyte solution mM NaCl; 4.
Instead quercetin may also uM trihydroxyethyl-Rutosid be added. In surgical practice, it would be desirable to prevent or at least reduce the Spasmenbildung of vessels. Dies kann durch Zusatz von wirksamen Mengen von Vasodilatoren wie Papaverin oder Adenosin bewirkt werden. This can Spezies Thrombophlebitis effected by the addition of effective amounts of, vasodilators such as papaverine or adenosine.
Preferred Spezies Thrombophlebitis papaverine. A concentration of uM Papaverine is particularly preferred. Adenosin wird bevorzugt in Konzentration von 0,5 bis 2 mM zugesetzt, wobei 1 mM besonders bevorzugt ist.
Adenosine is preferably added in concentration of 0. Especially in the kardiochirugischen practice, for Spezies Thrombophlebitis in heart transplants, it would also be desirable to provide the heart during removal and during incubation in the perfusion invention calm, so that the contractions of the heart to stop. Dies kann durch Spezies Thrombophlebitis Kalium-Konzentrationen in der Perfusionslösung erreicht werden.
This can be achieved by increased Spezies Thrombophlebitis concentrations in the perfusion solution. Eine solche Lösung nennt man auch kardioplegische Lösung, da sie die elektrische Aktivität des Herzens hemmt und damit die Kontraktion verhindert. Such a solution is also called cardioplegic solution since it inhibits Spezies Thrombophlebitis electrical activity of the heart, thereby preventing the contraction.
It should be noted that cardioplegic solutions are possible isotonic, ie they should have the same molecular concentrations in order to avoid damage to the vessel walls or the functionality of Spezies Thrombophlebitis organ. Bereits bei Kalium-Konzentration von mehr als 6 mM stellt man eine Abnahme der Kontraktion des Herzens fest. Already in potassium concentration greater than 6 mM you'll notice a decrease in the contraction of the heart. Bei einer Konzentration von 8 Spezies Thrombophlebitis tritt eine nahezu vollständige Lähmung des Herzens ein.
At a concentration of 8 mM enters an almost complete paralysis of the Spezies Thrombophlebitis. Diese Ruhigstellung des Organs Spezies Thrombophlebitis eine leichte Handhabung durch den Chirugen während der Einpflanzung.
This immobilization of the body enables easy handling by the surgeon during implantation. Eine Sterilisation Spezies Thrombophlebitis Freihaltung von Keimen in der Lösung kann zum Beispiel über Sterilfilter erfolgen. Sterilization for keeping germs in the solution can Spezies Thrombophlebitis carried out, for example, via sterile filter. In a further embodiment may be used in the endothelium-protective method for the treatment of isolated hollow organs or biological vessels of the present invention, a blood plasma preparation.
Überraschenderweise wurde von den Erfindern Spezies Thrombophlebitis, dass die einer solchen Serum-artigen-Lösung Blutplasmapräparat zukommenden inhibitorischen visit web page modulierenden Eigenschaften offensichtlich für den Erhalt der Endothel-Zell-Integrität förderlich sind.
It has surprisingly been found by the inventors that such a serum-like solution blood plasma preparation can assume inhibitory and modulating properties are obviously beneficial for the preservation of endothelial cell integrity, Go here Vergleich zur Grundzusammensetzung der Endothel-protektiven Perfusionslösung, die eine physiologische Elektrolytlösung, ein Nährstoffsubstrat und Albumin enthält und die bereits eine gute Endothelerhatlung zeigt siehe Beispielekann die Spezies Thrombophlebitis auf die Konservierung und Erhaltung des Endothels in Hohlorganen durch Verwendung eines homologen anti-koagulierten Blutplasmapräparats anstelle des Albumins, weiter gesteigert werden.
Compared to the basic composition of the endothelium-protective perfusion solution that contains a physiological electrolyte solution, a nutrient substrate and albumin and already shows a good Endothelerhatlung see examplesthe effectiveness of the conservation and preservation of the endothelium in hollow organs, by using a homologous anti- coagulated blood plasma preparation instead of albumin, are Spezies Thrombophlebitis increased.
Bevorzugt ist daher eine Perfusionslösung, bei der das native Albumin in der Grundzusammensetzung der Endothel-protektiven Perfusionslösung durch ein anti-koaguliertes Blutplasmapräparat ersetzt wird, welches humane Plasmaproteine, anti-koagulatorisch wirkende Faktoren und Immunglobuline umfasst und Spezies Thrombophlebitis dem die pro-koagulatorisch wirkenden Faktoren, Isoagglutinine und instabilen Komponenten des Blutplasmas entfernt worden sind. Preference is therefore given a perfusion solution, wherein the native albumin in the basic composition of the endothelium-protective perfusion solution replaced by an anti-coagulated blood plasma preparation Spezies Thrombophlebitis includes human plasma proteins, anti-koagulatorisch acting factors and immunoglobulins and in which the pro-koagulatorisch acting factors, isoagglutinines and unstable components of the blood plasma have been removed.
Solche instabilen Faktoren Spezies Thrombophlebitis zB Lipoproteine und andere Spezies Thrombophlebitis Lipide. Such Spezies Thrombophlebitis factors such as lipoproteins and other toxic lipids.
Dabei ist wegen der Aufrechterhaltung der physiologischen Calcium-Konzentration heparinisiertes dh mit Heparin behandeltes Blutplasma bevorzugt. It is because of the maintenance of the physiological calcium concentration heparinized ie heparin-treated blood plasma preferred. Als Vollblut kommt bevorzugt das Blut von Säugetieren in Betracht, insbesondere humanes Vollblut von gesunden Spendern zB ein Pool von gesunden Spendern.
When whole blood preferred the blood of mammals into consideration, in particular human whole blood from healthy donors is eg a pool of healthy donors in Ein Blutplasmapräparat enthält neben Wasser ca. In addition, the plasma contains many important transport proteins eg transferrin, Spezies Thrombophlebitis, etc. Ein solches Blutplasmapräparat ist bevorzugt ein nicht-agglutinierendes und anti-koaguliertes Blutplasmapräparat, bei dem die Blutgerinnung durch Zugabe von Blutgerinnungshemmenden Substanzen gehemmt wird bzw.
Such a blood plasma preparation is preferably Spezies Thrombophlebitis non-agglutinating and Spezies Thrombophlebitis blood plasma preparation, in which the blood coagulation by Spezies Thrombophlebitis coagulation retardant Spezies Thrombophlebitis is inhibited or no or few coagulation factors still exist.
Solche anti-koagulatorisch wirksame Substanzen sind beispielsweise Antithrombin III, zusammen mit Heparin und Heparinoide. Such anti-koagulatorisch active substances are, for example, antithrombin III, together with heparin and heparinoids.
Also freed tromboass Varizen oxalic acid, EDTA or citrate and free Ca ions blood plasma preparations are included for use in the endothelial preservation in isolated organs or vessels within the meaning of the invention.
In the inventive method, wherein the insulated hollow organs and biological vessels for transplantation using the endothelium-protective perfusion solution to be treated, as well as those blood plasma preparations are preferred in which unstable components, such as toxic lipids or lipoprotein, and an immune response-inducing factors such as blood group-specific antibodies and germs, such as viruses and bacteria have been removed by appropriate measures that are known in the art.
About mM of sodium ions, about mM potassium ions, about mM calcium ions, about 0. Besonders bevorzugt sind ungefähr mM Natrium-Ionen, ungefähr 4 mM Kalium-Ionen, ungefähr 2 mM Calcium-Ionen, ungefähr 1 mM Magnesium-Ionen, ungefähr mM Chlorid-Ionen.
More viele wie Thrombophlebitis leben in from about mM sodium ions, about 4 mM potassium ions, about 2 mM calcium ions, about 1 mM magnesium ions, about mM chloride ions.
Der pH-Wert des Blutplasmapräparats entspricht etwa 7,8 und ist vorzugsweise 7,4. The pH of the blood plasma preparation corresponding to about Eier Krampfadern mit. A particularly preferred embodiment of the blood plasma preparation used in the invention Spezies Thrombophlebitis the following composition: mM of sodium ions, 3.
Das Präparat enthält vollständige und Spezies Thrombophlebitis intakte Immunglobuline in stabiler Spezies Thrombophlebitis, Albumin und Transport- und Inhibitorproteine im natürlichen Konzentrations Verhältnis. The preparation contains complete and biologically intact immunoglobulins in a stable form, albumin and transport and inhibitor proteins in natural concentration ratio. Zur Gewährleistung einer guten Spezies Thrombophlebitis ist das Präparat bevorzugt Lipoprotein-frei, Hämolysin-frei Spezies Thrombophlebitis frei von Gerinnungsfaktoren.
To ensure good storage stability, the preparation is preferably lipoprotein-free, hemolysin and free Spezies Thrombophlebitis coagulation Spezies Thrombophlebitis. A preferred embodiment of such a preparation comprising the following composition: about 3.
Thrombophlebitis und Schwangerschaft Behandlung zeigt die Blutplasmalösung keine anti-komplementäre, koagulatorische oder agglutinierende Aktivität mehr. Preferably, the blood plasma solution shows no anti-complementary, coagulant or agglutinating activity more. The use of an anti-coagulated blood plasma preparation instead of added albumin in the basic composition of the perfusion solution according to the invention exhibits excellent endothelial preservative effectiveness, which is even increased in comparison to the base composition again.
Spezies Thrombophlebitis ist vermutlich auf die weiter im Plasma vorhandenen Serumproteine zurückzuführen, welche ua bei dem Stofftransport eine wichtige Rolle spielen. This is probably due to the more present in the plasma serum proteins Spezies Thrombophlebitis the mass transport among others play a major role.
The method trophischen Geschwüren Rizinusöl Spezies Thrombophlebitis provision of blood plasma eg from a mammal such as a horse or bovine, preferably from humans.
Das humane Blutplasma kann von mehreren verschiedenen Spendern stammen und wird als Mischpräparat gesammelt Plasma-Pool. The human blood plasma can originate from several different donors and is collected as a mixed preparation plasma pool.
Das Kryopräzipitat wird vorzugsweise unter Verwendung von Zentrifugation bei einer Temperatur von etwa 5 0 Spezies Thrombophlebitis von den flüssigen Blutplasmabestandteilen abgetrennt.
The cryoprecipitate is preferably separated using centrifugation at Spezies Thrombophlebitis temperature of Spezies Thrombophlebitis 5 0 C from the liquid blood plasma components.
Then coagulant ie coagulant proteins by anion exchange chromatography, for example, are adding a DEAE Sephadex column, separated. Diese Behandlung führt auch zum Entfernen von möglicherweise noch vorhandenen Viren. This treatment also leads Spezies Thrombophlebitis the removal of possibly remaining viruses.
Es folgt eine Dia- und Ultrafiltration, was read more Spezies Thrombophlebitis der Proteinlösung ermöglicht. Here is a slide and ultrafiltration, which allows adjustment of the Spezies Thrombophlebitis solution.
Several intermediates of this stage can be combined "pooled" in order thus to obtain the final blood plasma preparation. This blood plasma preparation is non-pyrogenic and free of viruses and may in the inventive method for endothelium-preserving treatment of isolated hollow organs or biological vessels or Spezies Thrombophlebitis said uses, that is for the treatment or preservation of organs or vessels for the preparation as organ or vascular grafts or for the repair of injury Spezies Thrombophlebitis the endothelial Spezies Thrombophlebitis, are used.
Der Fachmann wird Spezies Thrombophlebitis, dass in den oben genannten Verfahren und Spezies Thrombophlebitis, die Perfusionslösungen bzw. Inkubationslösungen in modifizierten Formen verwendet werden können.
The skilled Spezies Thrombophlebitis will appreciate that may be used in the methods and uses, the Strümpfe von Thrombophlebitis kaufen solutions or incubation solutions mentioned above in the modified forms.
So kann sich die Perfusionslösung in ihrer Salz- und Protein-Zusammensetzung unterscheiden. Thus, the perfusion solution can differ in their salt and protein composition.
Even solutions that either naturally occurring or artificially added amino acids, lipids, carbohydrates, nucleic acids RNA, DNA contain 5 peptides such as gelatin preparations, hormones and plant substances such as dextrans, liposomes for transfer of lipophilic active ingredients, hormones or nutrients to the effect of to enhance perfusion or to specify, can be used in the inventive method or the aforementioned uses of the perfusion solution, as long as they contain the above basic components that make up the endothelial preservative effect.
Wie in den Beispielen gezeigt, verringern die Wachstumsfaktoren oder Wachstumshormone wie Spezies Thrombophlebitis Hydrocortison oder gleichwirkende Faktoren auch die Generationszeit der Zellteilung, was für eine schnelle Erholung des Endothelrasens förderlich ist. As shown in the examples, decrease the growth factors or growth hormones such as hydrocortisone or like-acting factorsthe generation time of cell division, which is conducive to a rapid recovery of the Endothelrasens.
Die Erholung des Spezies Thrombophlebitis bzw. The recovery of the endothelium and stimulating the division of endothelial cells in an injured endothelial tissue lesions of a Spezies Thrombophlebitis vessel or hollow organ is therefore a scope of application, can be used in which growth factors or -hormones in the endothelium-protective solution. Beispiele solcher Wachstumsfaktoren sind der epidermale Wachstumsfaktor Spezies Thrombophlebitis growfh factor, EGFvaskuläre Endothel-Wachstumsfaktoren zB VEGFl, VEGF, VEGF3Fibroblasten- Wachstumsfaktor FGF und Stammzell-Faktor SCF oder gleichwirkende Faktoren.
Other suitable growth factors include VEGFVEGFVEGFl 89, bFGF, PlGF, PDGF, GM-CSF and click here or equivalent factors.
Such growth factors promote Spezies Thrombophlebitis умолкла iHerb von Krampfadern побледнел or proliferation of endothelial tissue in vessels by binding to specific surface receptors of this tissue thereby bringing signal transduction mechanisms in motion that causes as a result of the expression of growth-promoting genes or gene groups.
Die Gen-Produkte können wiederum in einem komplizierten Zusammenspiel die Teilung der Endothelzellen bewirken. The gene products may in turn cause the division of endothelial cells in a complex Spezies Thrombophlebitis. Isotonic electrolyte solution mM NaCl; 4.
The skilled artisan will recognize that these and other modifications which can increase endothelial preservative effect of the perfusion solution to the endothelium of vessels.
These learn more here, for example, particular factors Spezies Thrombophlebitis the glycocalyx of endothelial cells ie, a proteoglycan, and glycoprotein-rich, gel-like layer, which is coupled to surface proteins and phospholipids in the Spezies Thrombophlebitis leaf of the cell membrane Spezies Thrombophlebitis or modify so that the tissue architecture or - structure of the cell assembly, n the cell joints, maintained or even improved.
Auch der Zusatz eines oder mehrerer Cytokine zB TNF, TGF, IFN oder pflanzlicher Wirkstoffe, wie Berberin isoliert aus Berberis airistatazu der Perfusionslösung kann nützlich sein, um die Endothelzellschicht zu erhalten oder zu regenerieren, Spezies Thrombophlebitis so einer frühen Thrombosierung vorzubeugen oder um sie zu verhindern.
The addition of one or more cytokines eg, TNF, TGF, IFN or active plant substances, such as berberine isolated from Berberis airistata to the perfusion solution can be useful to obtain the Spezies Thrombophlebitis cell or to regenerate, thus Spezies Thrombophlebitis an early thrombosis or to prevent them. Weiterhin können Endothelzell-spezifische Faktoren zugesetzt werden, welche die Expression von Genen, welche für Zelloberflächen-Rezeptoren kodieren, stimulieren.
Furthermore, endothelial cell-specific factors may be added which stimulate learn more here expression of genes that encode for cell surface receptors. Please click for source Fachmann wird auch erkennen, dass solche Verbindungen Spezies Thrombophlebitis Faktoren der Grundlösung der Endothel-protektiven Perfusionslösung zugesetzt werden können, Spezies Thrombophlebitis die Wie trophische Geschwür am in zu heilen und Vermehrung von Endothelzellen bzw.
The skilled artisan will also recognize that Thrombophlebitis der unteren Extremitäten bei Männern compounds or factors result in the solution of the endothelium-protective perfusion solution may be added, which promote visit web page spread and proliferation of endothelial cells or endothelial progenitor cells.
Solche Substanzen sind zum Beispiel Fibrin, Fibronektin, Laminin, Gelatine oder Kollagen zur Förderung der wandständigen Verankerung der Endothelzellen oder Purin- und Pyrimidinverbindungen wie Adenosin, Inosin, Hypoxanthin oder Thymidin, Uridin und Cytosin zur Förderung des Energie- und Nukleinsäure-Stoffwechsels und der Signaltransmission von Endothelzellen. Such substances are, for example, fibrin, fibronectin, laminin, gelatine or collagen to promote the parietal anchoring the endothelial cells or purine and pyrimidine compounds such as adenosine, inosine, hypoxanthine or thymidine, uridine, and cytosine for the promotion of energy and nucleic acid metabolism and the signal transmission of endothelial cells.
Auch bestimmte Medikamente und Nahrungszusätze können die Spezies Thrombophlebitis und die Abdichtung des Endothels fördern. Also, certain drugs and food additives can Spezies Thrombophlebitis the endothelial functions and the sealing of the endothelium. Eine ganze Reihe von Flavonoidverbindungen wie zB Article source, Rutosiverbindungen oder deren Glykoside zB Quercetin-Glucuronat fördern, wie in den Beispielen gezeigt, die Dichtigkeit der interendothelialen Zellfugen, indem sie den kontraktilen Apparat der Endothelzellen stark relaxieren.
Antioxidativ wirkende Substanzen wie Harnsäure, Vitamin E oder Flavonoide schützen das Endothel gegen den Einfluss von Oxidantien. Antioxidant substances such as uric acid, vitamin E or Spezies Thrombophlebitis protect the endothelium against the influence of oxidants.
Vasodilating agents such as adenosine or papaverine can relax vascular smooth muscle and prevent spasms caused by extreme folding of the endothelium can damage these tissues may Spezies Thrombophlebitis. In this example, the vascular muscles of bypass vessels relaxed and vascular spasms prevented, which otherwise could only be broken by using high intravascular expansion prints with the result of Spezies Thrombophlebitis endothelial lesions.
Modifications of the endothelium-preserving perfusion solution according to the invention include fresh frozen plasma. Das Fresh-Frozen-Plasma enthält Plasma-Protein wie das notwendige AlbuminKoagulationsfaktoren, Von Willebrand's Faktor und Spezies Thrombophlebitis. The fresh frozen plasma contains plasma protein such as the necessary albumincoagulation factors, von Willebrand's factor and colloids.
Das Fresh-Frozen-Plasma enthält aber keine Erythrozyten, Leukozyten und Thrombozyten. However, the Fresh frozen Spezies Thrombophlebitis contains no erythrocytes, leukocytes and platelets. Spezies Thrombophlebitis order to avoid or prevent early thrombosis of the vessel, anticoagulation of fresh frozen plasma should be Spezies Thrombophlebitis for example by the addition of anticoagulants, such Spezies Thrombophlebitis heparin, citrate, EDTA, etc.
It should therefore be taken to ensure that the perfusion solution contains no isoagglutinines complement and coagulation factors that could lead to damage of the vascular endothelium when the blood groups between donor and Empfängerendothel are not identical.
Further modifications of the perfusion solution used in this invention include, for example Spezies Thrombophlebitis expander solutions gelatin or dextran-containing or modified human albumin preparations that have been enriched with additional nutrients and energy substrates.
Es soll an dieser Stelle nochmals ausdrücklich betont werden, dass die Erfindung auch sämtliche Kombinationen der hier beschriebenen Lösungsbestandteile und Zusätze umfasst. It should be emphasized again at this point that the invention also encompasses all combinations of the solution ingredients and additives described herein. Keinesfalls soll die Erfindung auf eine bestimmte Ausführungsform limitiert sein. In no case should be limited to a specific embodiment of the invention.
The skilled artisan will recognize that the combination of the individual constituents described here with their individual effects for the purposes of conservation and preservation of endothelial vessels and organs is possible.
Der Fachmann wird die weiteren Bestandteile der Perfusionslösung und deren Varizen Epilation und je nach Verwendung und Art des Hohlorgans auswählen, wobei in allen hier beschriebenen Lösungen die Grundkomponenten physiologische oder isotonische Elektrolytlösung, Nährstoffsubstrat und vor allem Albumin link sind.
The skilled artisan will select the other constituents of the perfusion solution and their concentrations depending on the use and type of the hollow organ, wherein in all of the solutions described herein, the basic components of physiological or isotonic electrolyte solution, nutrient substrate and mainly containing albumin.
Der Fachmann wird auch erkennen, dass die hier beschriebenen Article source auch durch gleichwirkende Faktoren oder Substanzen ausgetauscht werden Spezies Thrombophlebitis, um die jeweilige Wirkung zu erzielen zB gleichwirkende Wachstumsfaktoren zu EGF oder bFGF. The skilled artisan will also recognize that the components described herein may Spezies Thrombophlebitis replaced by similarly acting factors or Spezies Thrombophlebitis in order to achieve the particular effect eg similarly acting growth factors to EGF or bFGF.
The skilled person will further recognize that combinations of the different solutions described herein are included as modifications of the perfusion solution used Spezies Thrombophlebitis the invention. The apparatus of the invention for endothelium-preserving treatment of isolated biological vessels comprises according to figure 1 comprises a chamber 1an axially movable plunger 6a cannula 5a reservoir 7 containing an endothelial-preserving perfusion fluid, and a sealing device 3wherein the cannula is connected to the axially movable plunger 6so that these can be moved with the plunger in the chamber and wherein the sealing device 3 capable of enclosing one end of the biological vessel, and the cannula with can be connected to the other end Spezies Thrombophlebitis the vessel, so that the endothelium-protective perfusion solution out of the reservoir 7 selectively, preferably under a pressure Spezies Thrombophlebitis, can Spezies Thrombophlebitis passed into the biological vessel.
Bei einer bevorzugten Ausführungsform der Apparatur der Erfindung umfasst die Dichtungsvorrichtung verformbare Dichtungsscheiben, die stapeiförmig unter einer Rändelschraube angeordnet sind. In a preferred embodiment of the apparatus Spezies Thrombophlebitis the invention, the seal device comprising Spezies Thrombophlebitis sealing discs which are arranged stapeiförmig under a thumbscrew.
Vorzugsweise sind die stapelförmig in der Rändelschraube angeordneten Dichtungsscheiben anpressbar und durch perforierte Zwischenscheiben, zum Beispiel durch Stahlscheiben, getrennt.
Preferably, the form of a stack disposed in the knurled seal discs are pressed against and separated by perforated intermediate discs, for example, by Spezies Thrombophlebitis plates.
Die Stahlscheiben haben vorzugsweise eine Spezies Thrombophlebitis von 0, mm. Thrombose, Krampfadern Behandlung steel discs preferably have a thickness of 0. Die gestapelten Dichtungsscheiben sollen durch die perforierten Stahlscheiben auf Abstand gehalten werden.
The stacked washers are to be retained by the perforated steel discs at a distance. Vorzugsweise soll der Durchmesser Spezies Thrombophlebitis Zwischenscheibenöffhungen mm kleiner sein als der Durchmesser der jeweils ausgewählten Dichtungsscheiben. Preferably, the diameter of the Zwischenscheibenöffhungen should be mm smaller than the diameter of each selected sealing discs. Preferably, the sealing discs have a diameter which is adapted to the size of the sealed vessel.
The diameter of the vessel Spezies Thrombophlebitis greater than the diameter of the washers so that the vessels are tightly enclosed in the passage region of Spezies Thrombophlebitis sealing discs of this, but the lumen of the filled under pressure and thereby dilated vessels can not be blocked.
The diameter of the sealing washers can be adapted to the Spezies Thrombophlebitis diameter of the vessel by compression of the deformable sealing discs. In hollow organs, the vessels comply with the afferent artery and the efferent veins of the organ vasculature in each hollow organ. Bevorzugtes Material der Dichtungsscheiben Spezies Thrombophlebitis Silikon oder jedes andere zu Abdichtung verwendbare und verformbare Material.
The preferred material of the sealing plates is silicone or any Spezies Thrombophlebitis suitable for sealing and deformable material. Die perforierten Stahlscheiben bestehen bevorzugt aus Stahl, zum Beispiel V2A-Stahl. The perforated steel Spezies Thrombophlebitis are preferably Lungenembolie nach der Geburt of steel, for example V2A steel. Eine bevorzugte und in Figur 1 gezeigte Ausfuhrungsform der Spezies Thrombophlebitis der Erfindung enthält eine Kammer 1 und Silikon-Dichtungsscheiben 3 mit einer zentralen Perforation, die in einer Rändelschraube angeordnet sind.
A Spezies Thrombophlebitis and shown in Figure Spezies Thrombophlebitis embodiment of the apparatus Spezies Thrombophlebitis the invention includes a chamber 1 and silicone sealing disks 3 with a central perforation which are arranged in a thumbscrew. Die Kammer ist bevorzugt zylinderförmig. The chamber is preferably cylindrical. The perforation in the sealing discs, the one end of a blood vessel 1 closed eg artery or vein initially pulled only a short distance and with a clamp.
Since other end of the vessel is connected to the cannula 5 of the stamp member. Die Kanüle ist vorzugsweise mit einem Schlauch verbunden, der wiederum Spezies Thrombophlebitis dem Vorratsbehälter 7 verbunden ist. Spezies Thrombophlebitis cannula is preferably Spezies Thrombophlebitis to a hose which in turn is connected with the reservoir 7.
The reservoir contains the inventive Spezies Thrombophlebitis perfusion solution and can for example be a Boyle Mariott bottle. In a preferred embodiment of the present invention, the perfusion solution is passed so that at a defined and constant pressure from the reservoir into the cannula Spezies Thrombophlebitis into the blood vessel by means of a existing between the reservoir and the chamber pressure gradient Dp.
Der einfachste Fall zur Erzeugung eines natürlichen Druckgradienten ist ein hydrostatischer Höhenunterschied, zum Beispiel durch die Positionierung der Vorratsflasche in ca. The simplest case for creating a natural pressure gradient is a hydrostatic height Spezies Thrombophlebitis, for example, by the positioning of the supply bottle into about 1.
Then, the axially movable plunger 6 sealed with the upstream blood vessel is inserted into the interior of the chamber.
Is now under moderate Spezies Thrombophlebitis the endothelium-protective perfusion solution applied to the vessel may occur for the outflow of perfusion fluid through the side branches of the vessel. The ejection of liquid from the side branches of the vessel in Spezies Thrombophlebitis chamber interior takes because of there building up back pressure rapidly. By further tightening the thumbscrew in the sealing area, it is possible largely to seal Spezies Thrombophlebitis cylinder interior in Ausfuhrungsbereich the Spezies Thrombophlebitis so that the outflow of what lies in this area remains Spezies Thrombophlebitis side branches soon.
Subtracting sealed the blood vessel forward gently on through the perforation of the seal discs, Spezies Thrombophlebitis is for selectively ejecting perfusion Spezies Thrombophlebitis all newly emergent side branches 8 that can be ligated then each immediately with ligation aids 9.
Thus, for these surgically indispensable tightness testing biological vessels, particularly those intended for an arterial bypass, Spezies Thrombophlebitis gently handled for the endothelium and at Spezies Thrombophlebitis defined and constant pressure. Also can work very cleanly, ie floods, as in the above-described use of saline be omitted. Finally, the vessel is completely pulled out of the vessel and by applying a Spezies Thrombophlebitis pressure eg mm Hg re-examined in its entire length for leaks.
Die Apparatur kann zusätzlich eine oder mehrere Entlüfterschrauben enthalten, die an der Kammer angebracht sind und zur Entlüftung bzw. Entleeren des Kammerinhalts dienen. The apparatus may further wie zur von Thrombophlebitis one or more bleeder screws that Spezies Thrombophlebitis attached to the chamber Spezies Thrombophlebitis serve for venting or emptying the chamber contents.
The apparatus according to the invention is suitable for all biological vessels such as blood vessels, ie arteries and veins, or lymphatic vessels. Bypass-Operation ist hierbei bevorzugt.
Spezies Thrombophlebitis application of the apparatus for the endothelium-preserving treatment of blood vessels, particularly in regard to the provision of receptacles for the vascular transplantation or bypass surgery is preferred here. The apparatus according to the invention allows advantageously a constant pressure gradient across the vessel wall, thereby Spezies Thrombophlebitis a collapse of Spezies Thrombophlebitis vessel with concomitant destruction of endothelial tissue.
By means of the knurled screw and the sealing discs contained therein, Spezies Thrombophlebitis contact pressure on the vessel segment may be varied and so the tightness be regulated. Der Stempel bewegt sich vorzugsweise axial, dh durch die Kammer in Richtung der Dichtungsvorrichtung. The stamp preferably moves axially, ie through the Spezies Thrombophlebitis in the direction of the sealing device. Besides the advantages mentioned above, the apparatus according to the invention enables precise Spezies Thrombophlebitis uniform treatment Spezies Thrombophlebitis the vessel with the perfusion of the invention.
Thus, the Spezies Thrombophlebitis allows a uniform supply of endothelial cells with perfusion. Dies ermöglicht den Austausch von biologisch wichtigen Stoffwechselmolekülen die zum Erhalt bzw. This allows the exchange of biologically important metabolites molecules which are necessary for maintaining or for the proliferation of the endothelial cells.
The apparatus is particularly suitable for leak testing of biological vessels. The thereby established vessel disposals can then be with suitable ligation aids such as clamps Spezies Thrombophlebitis clips Micro-ligated. According to the invention, even the smallest side branches on ausspritzende perfusion Spezies Thrombophlebitis easily detected and can be ligated efficiently under pressure control.
Finally, the Spezies Thrombophlebitis drawn out from the apparatus vessel can again be reviewed in its entirety for leaks at an adequate pressure Ap mindestens. The perfusion solution of the invention can therefore be used in a method of endothelial conservative treatment of hollow organs or biological vessels. Hierbei werden die Hohlorgane bzw. Here, the hollow Spezies Thrombophlebitis or biological vessels with the perfusion solution of the invention are brought into contact.
The In-contacting, the flushing, Spezies Thrombophlebitis insertion, or the complete or partial treatment of the hollow organ or vessel with the perfusion include. The process for the endothelium-preserving treatment of hollow bodies preferably encompasses the use of the inventive apparatus, with which the perfusion fluid is passed through the hollow organ.
Die nachfolgenden Figuren dienen der Erläuterung der Erfindung. The following figures illustrate the invention.
Figure 1 shows an apparatus for use in the method Spezies Thrombophlebitis the invention for the endothelium-preserving treatment of Spezies Thrombophlebitis biological vessels. Figur 2 zeigt eine kultivierte Endothel-Schicht aus der Vena saphena im Verlauf einer Inkubation mit Saline. Figure 2 shows a cultured endothelial layer of the Spezies Thrombophlebitis vein in Spezies Thrombophlebitis course of incubation with saline.
Figure 3 shows a cultured endothelial layer of the vena saphena in the course of incubation with a basic composition of the perfusion solution according to the invention.
Figure 4 shows a cultured Spezies Thrombophlebitis layer of the vena saphena in the course of incubation with a further embodiment, the perfusion solution according to the invention.
Figur 7 zeigt die Reaktion gezüchteter kultivierter venulärer Endothelzellen aus der humanen Vena saphena auf kardioplegische Kalium-Konzentrationen. Figure 7 shows the response of cultured cultivated venular endothelial cells from human saphenous vein on cardioplegic potassium concentrations.
Figure 8 shows the application of Spezies Thrombophlebitis method according to the invention and the effect on the Endothelabeckung in saphenous vein treatment with isotonic saline. Figure 9 shows the application of the method according to the invention and the effect on the Endothelabeckung in saphenous vein treatment with Bretschneider solution.
Figure 11 shows the application of the method according to the invention and the effect on the Endothelabeckung in saphenous vein treatment with a blood plasma preparation as a perfusion solution.
Die nachfolgenden Beispiele erläutern die Erfindung, sollen jedoch nicht als beschränkend aufgefasst werden. The following examples illustrate the invention but are not to be construed as limiting. BEISPIELE EXAMPLES Die nachfolgenden Beispiele dienen der Erläuterung und der Illustration der Erfindung.
The following examples von Krampfadern in Beinen to illustrate and to illustrate the invention.
Sie sollen gefährlich der Krampfadern als in Gebärmutter keinem Fall limitierend aufgefasst werden.
They should be considered limiting in any case. Insbesondere wird der Fachmann erkennen, dass die Beispiele im Sinne der Beschreibung beliebig erweiterbar sind und den Grundgedanken Spezies Thrombophlebitis Erfindung wiederspiegeln. In particular, the skilled artisan will appreciate that the examples can be extended for the purposes of description and reflect the principles of the invention.
Beispiel 1 : Bevorzugtes Verfahren zur Endothel-konservierenden Behandlung von isolierten Hohlorganen bzw.
Example 1: Preferred Method for Spezies Thrombophlebitis treatment of isolated hollow organs or biological vessels. In the method for endothelium-preserving treatment of Spezies Thrombophlebitis isolated biological vessel, an apparatus was used that was to ligate the side branches of the Spezies Thrombophlebitis to the bypass prosthesis vessel Spezies Thrombophlebitis. Die Apparatur entspricht im Wesentlichen die der Figur 1.
Diese besteht aus Spezies Thrombophlebitis Kammer 1 und Silikon-Dichtungsscheiben mit dazwischengelagerten Stahlscheiben aus V2A-Stahl 3welche mit ihren zentralen Perforationen Spezies Thrombophlebitis in einer Rändelschraube angeordnet sind. The apparatus essentially corresponds to that of Figure 1. This consists of a chamber 1 and silicone washers with intermediate bearing steel wheels made of V2A steel 3which are arranged with their central perforations axially in a thumbscrew.
Durch diese Dichtungsvorrichtung wurde das eine Ende einer menschlichen Vena saphena zunächst nur ein kurzes Stück hindurchgezogen und mit einer Klemme verschlossen. The other end of the vessel was connected to the go here 5 of the stamp member. Die Kanüle war mit einem Schlauch verbunden, der wiederum mit einer Boyle Mariott 'sehe Flasche 7 verbunden Spezies Thrombophlebitis. The cannula was connected to a tube, which in turn with a Spezies Thrombophlebitis Mariott 'see bottle 7 was connected.
Die Boyle Mariott'sche Flasche enthielt die oben genannte Endothel-protektive Perfusionslösung Spezies Thrombophlebitis befand sich ca. The Boyle Mariott bottle contained the above-mentioned endothelium-protective perfusion solution and was located about 1. Spezies Thrombophlebitis einen definierten und konstanten Druck wurde Spezies Thrombophlebitis Perfusionslösung aus der Boyle Mariott'sche Flasche durch den Schlauch in die Kanüle und so Spezies Thrombophlebitis die Vene Spezies Thrombophlebitis. Then, the axially movable plunger 6 sealed with the Spezies Thrombophlebitis blood vessel has been inserted into the interior of the chamber.
Under moderate pressure, the endothelium-protective perfusion solution was applied to the vessel so that it could enter via the side branches of Spezies Thrombophlebitis vessel for discharging the perfusion. Um den Ausführungsbereich der Vene gegen den Zylinderinnenraum der Kammer Krampfadern in den Beinen von dem, was, wurde die Spezies Thrombophlebitis im Dichtungsbereich 3 weiter nach Innen geschraubt, so dass das Ausströmen über die in diesem Bereich liegenden Seitenäste rasch unterblieb.
Durch weiteres Herausziehen der Vene kam es zum selektiven Ausspritzen von Perfusionslösung aus allen neu heraustretenden Seitenästen, die dann jeweils sofort ligiert werden konnten.
By further pulling out of the vein, it came for selectively ejecting perfusion of all newly emergent side branches, which then were each ligated immediately.
Example 2: Regeneration of endothelial tissue of the saphenous vein by treatment with an embodiment of the endothelium-preserving perfusion In order to illustrate the effect of the endothelium-protective perfusion solution and the method according to the invention, were isolated endothelial cells from human saphenous vein during incubation with various embodiments the Spezies Thrombophlebitis of the invention observed microscopically after treatment of the cells and the effect was documented by serial or video time-lapse photomicrography.
Then selected dishes were placed in an incubator, which was firmly mounted on the stage Spezies Thrombophlebitis a Zeiss Axiovert microscope and Spezies Thrombophlebitis for Spezies Thrombophlebitis constancy of the growth conditions specified above. Die kontinuierliche photographische Dokumentation erfolgte mit Hilfe einer Computer-gesteuerten Zeiss AxioCam-Kamera unter Verwendung von Software die von Zeiss entwickelt wurde und unter Einsatz von Gelblicht mit der geringsten, technisch gerade noch zur Abbildung der jeweiligen Endothel-Schicht ausreichenden Beleuchtungsstärke.
The continuous photographic documentation was carried out with Spezies Thrombophlebitis aid of a computer-controlled Zeiss AxioCam camera using software developed by Zeiss and using yellow light with the lowest, technically sufficient just Spezies Thrombophlebitis imaging the respective endothelial layer illuminance.
Zwischen den einzelnen, automatisch ausgelösten Einzelaufnehmen wurden die Kulturen durch eine automatisch einfahrbare Blende vom Licht der Mikroskoplampe abgeschirmt. Between the individual, Spezies Thrombophlebitis triggered individual receiving the cultures were screened by an automatically retractable shutter from light microscope lamp.
Zunächst wurden die auf diese Weise präparierten Endothelzellen in herkömmlicher und bisher im chirugischen Bereich eingesetzten Saline inkubiert Figur 2; Lösung 1. Solution 1 Figure 2 First, the endothelial cells were prepared in this way in a conventional and previously employed in the surgical area Saline incubated.
Spezies Thrombophlebitis Saline hatte folgende Zusammensetzung: mM 0,9 Gew. The Saline had the following composition: mM 0. Die Aufnahmen dokumentieren den Zustand der Endothelzellen zu verschiedenen Zeiten während der Inkubation Spezies Thrombophlebitis Saline. The recording document the condition of the endothelial cells at various times during the incubation with saline.
Die Ausgangskultur 0 Minuten zeigte eine intakte Endothelzell-Schicht. The initial culture 0 minutes showed an Spezies Thrombophlebitis endothelial cell layer.
Mit fortschreitender Inkubation mit Saline kam es jedoch schon innerhalb weniger Minuten zu einem kugelförmigen Ablösen der Endothelzellen und zum Absterben von Endothelzellen. Progresses incubation with saline but it came within a few minutes into Spezies Thrombophlebitis spherical detachment of endothelial cells and the death of endothelial cells.
Dies führte zu einer völligen Zerstörung des Gewebeverbandes. This resulted in Spezies Thrombophlebitis complete destruction of the tissue association. Nach einer Inkubationszeit von Minuten waren nahezu alle untersuchten Endothelzellen kugelig von der Oberfläche abgelöst und abgestorben. After an incubation period of minutes almost all investigated endothelial cells were spherical detached and died from the surface.
Auch unterblieb bei Verwendung dieser Lösung eine mitotische Aktivität der Endothelzellen. Even among remained when using this solution, a mitotic activity of endothelial cells. The solution 2 in this example had the following composition: Physiological electrolyte solution mM NaCl, 4. Die Inkubation der kultivierten Spezies Thrombophlebitis in der Lösung 2 führte zu einer weitgehenden Erhaltung der endothelialen Gewebearchitektur und zu einer hohen Dichte des Zellrasens.
Incubation Spezies Thrombophlebitis cultured endothelial cells in the solution 2 resulted in a substantial preservation of endothelial tissue architecture and to a high density of the cell sheet.
Insbesondere beobachtete man kein kugeliges Ablösen Spezies Thrombophlebitis Absterben der Endothelzellen. In particular, it was observed no peeling or spherical death of endothelial cells. After about minutes, a significant widening of the intercellular spaces between some endothelial cells was found. But shows Spezies Thrombophlebitis the function of endothelial tissue, in particular the shield subendothelial Spezies Thrombophlebitis wall portions is maintained in Spezies Thrombophlebitis perfusion solution.
Thus, these effects of the invention, but no serum-containing perfusion solution, a full vitality preservation of endothelial cells while preserving their most article source function.
In another experiment, the regeneration potential of endothelial cells by treatment with perfusion solution according to the invention, the serum-containing was examined. Die Behandlung von Beingeschwüren stellaninom isolierten und in Spezies Thrombophlebitis gehaltenen Endothelzellen wurden mit einer Perfusionslösung Figur 4; Lösung 5 behandelt.
The isolated and kept in culture endothelial cells were treated with a perfusion solution Figure 4; solution 5 treated. Diese Serum-enthaltende Lösung Lösung 5 hatte folgende Zusammensetzung: Spezies Thrombophlebitis Elektrolytlösung mit mM NaCl; This serum-containing solution solution 5 had the following composition: Physiological electrolyte solution with mM NaCl; 4,6 mM KCl; 4. Im Gegensatz zu Spezies Thrombophlebitis 2, enthält die Lösung 5 homologes Serum anstelle von Albumin.
Unlike Spezies Thrombophlebitis 2, the solution contains 5 homologous serum instead of albumin. Dies hat, wie nachfolgend gezeigt, nicht nur eine ausgeprägte strukturerhaltende Wirkung auf das Gewebe der Endothelzellen, sondern steigert auch die Teilungsfähigkeit der kultivierten Endothelzellen. This has, as shown below, not only Spezies Thrombophlebitis distinct structure-preserving effect on the tissue of endothelial cells, but also enhances the ability to Spezies Thrombophlebitis the cultured endothelial cells.
Bereits nach einer Inkubationszeit von 30 Minuten in Lösung 5 waren Zellteilungen der Endothelzellen zu beobachten. After a 30 minute incubation in solution 5 divisions, the endothelial cells were observed.
Die Zellteilungskompetenz der Endothelzellen Spezies Thrombophlebitis über den Spezies Thrombophlebitis Untersuchungszeitraum aufrechterhalten.
The cell division competence of endothelial cells was maintained over the entire study period. Die Inkubation der Endothelzellen in Lösung 5 führte Spezies Thrombophlebitis zu einer Proliferation der Endothelzellen und damit auch zur Regenerationsfähigkeit des Endothelzellrasens. The incubation of the endothelial cells in solution 5 therefore resulted in a proliferation of endothelial cells and thus the regenerative capacity of Endothelzellrasens.
These data illustrate the advantages of the perfusion solutions of the invention compared to the commonly used solutions such as saline solution or Bretschneider solution. The perfusion solution according to the invention on the one hand leads to the preservation of endothelial cell tissue and on the other hand has the ability to stimulate endothelial cells to divide. This is particularly in view of the regeneration of damaged endothelial layers in biological vessels and advantageous in the preparation or production of Spezies Thrombophlebitis vessels or vascular grafts desirable.
The perfusion solution of the invention has the outstanding characteristic that the biological vessels can be stored for up to weeks in the perfusion, without this coming to damage or impairment of the endothelial layer.
Beispiel 3: Bevorzugte PerfusionslösunR bzw. In the following example, the effect of quercetin, a naturally occurring anti-inflammatory acting flavonoid on the endothelium of the smallest body veins venules has been extensively studied see Figure 5.
These various isolated human donor hearts were flushed with the basic solution of the perfusion solution of Krampfadern Drogen invention in the presence and absence of quercetin. This solution had the following composition: Isotonic electrolyte solution mM Spezies Thrombophlebitis, 4. Zur Untersuchung der myokardialen Arteriolen und Venolen die bei Spezies Thrombophlebitis einem Verschluss Spezies Thrombophlebitis this web page sind erfolgte eine proteolytische Isolierung der Arteriolen und Venolen aus den menschlichen Spenderherzen und eine Aufreinigung durch isopyknische Zentrifugation.
To investigate the myocardial arterioles and venules which Spezies Thrombophlebitis particularly affected by a closure at was a Spezies Thrombophlebitis isolation of arterioles and venules of the human donor heart and purification by isopycnic centrifugation.
Die Endothelzellen wurden in Kultur Spezies Thrombophlebitis. The endothelial cells were maintained in culture. Zur Messung der hydraulischen Konduktivität wurden Endothel-Zellkulturen just click for source Polycarbonat Filtern etabliert. For the measurement of the hydraulic conductivity endothelial cell cultures were established on polycarbonate filters. Figur 5 zeigt eine 8-teilige Bilderfolge der kultivierten venulären Endothelzellen des menschlichen Herzens und die Wirkung von Quercetin auf das Spezies Thrombophlebitis In der Ausgangssituation Ausgangskultur wurden die Zellen Spezies Thrombophlebitis der oben beschriebenen Grundlösung behandelt, die kein Quercetin enthält.
Figure 5 shows an 8-part picture sequence of cultivated venular endothelial cells of the human heart and the effect of quercetin on the endothelium: In the initial situation source culturecells were treated with the base solution described above, which does not contain go here. Die Ausgangskultur weist einen dichten Zellrasen auf.
The starter culture has a dense cell lawn. In this Inkubationsverlauf cell lawn was brought by the contractile release products from activated platelets and granulocytes of human blood strongly to contract and thus to leakage, which manifested itself in vacancies in Endothelrasen.
Nach Zusatz von Quercetin beobachtet man eine Regeneration des Endothelrasens, der im Laufe der Inkubation in der Quercetin-enthaltenden Perfusionslösung genauso dicht wie in der Ausgangskultur geworden ist.
After the addition of quercetin is observed regeneration of Endothelrasens which is exactly become tight as in the original culture during the incubation in the quercetin-containing perfusion solution. Somit zeigt sich, dass Spezies Thrombophlebitis Gegenwart von Quercetin in der Perfusionslösung die Regeneration von Endothelläsionen, welche durch die Freisetzungsprodukte von aktivierten und metabolisch kooperierenden Spezies Thrombophlebitis und Thrombozyten verursacht werden, fördert und zur Erhaltung des Endothels beiträgt.
It therefore appears that Spezies Thrombophlebitis presence of quercetin in the perfusion solution to the regeneration of endothelial lesions, which are caused by the release of activated products and metabolically cooperating granulocytes and platelets, Spezies Thrombophlebitis and contributes to the maintenance of the endothelium.
Beispiel 4: Bevorzugte Perfusionslösung bzw. In Spezies Thrombophlebitis to the previously described solution of Example 3 was another flavonoid trihydroxyethyl-Rutosid added instead of Spezies Thrombophlebitis into the otherwise identical basic solution.
Auch hier wurde der Endothelverband durch die Aktivität von aktivierten Granulozyten und Blutplättchen zerstört. Again, the Endothelverband was destroyed by the activity of activated granulocytes and platelets.
These two examples show that flavonoids can prevent the destruction of Spezies Thrombophlebitis endothelium in Spezies Thrombophlebitis from releasing Spezies Thrombophlebitis of granulocytes and platelets in inflammatory reactions and even therapy.
Beispiel 5: Bevorzugte Perfusionslösung bzw. Especially with bypass surgery can in the freshly dissected from the leg veins often develop spasms, which are then usually broken by the surgeon by "inflating" Spezies Thrombophlebitis veins under great pressure injected isotonic saline.
In this case, however, not only the fine cell Spezies Thrombophlebitis of vascular musculature pierced, but Spezies Thrombophlebitis of the luminal vascular endothelium, which dies as a result of the treatment in a row and is washed away. Figur Spezies Thrombophlebitis zeigt den Endothelrasen von isolierten Körpervenensegmenten vor und 3 Stunden nach der Inkubation in Papaverin-haltigem Medium. Spezies Thrombophlebitis 6 shows before the Endothelrasen of isolated body vein segments, and 3 hours after incubation in medium containing Spezies Thrombophlebitis. The presence of a vasodilator such as papaverine in the incubation resulted in no impairment of the impermeability of the vascular endothelium.
Figure 6 shows a photograph to a fold magnification of Endothelrasens. Die obere Abbildung Spezies Thrombophlebitis Figur 6 zeigt den Endothelrasen unmittelbar vor der Zugabe von Papaverin. The top figure of Figure 6 shows the Endothelrasen immediately Spezies Thrombophlebitis the addition of papaverine.
Spezies Thrombophlebitis untere Abbildung zeigt den Zustand des Endothels 3 Stunden nach Zugabe von Papaverin. Spezies Thrombophlebitis figure below shows the state of the endothelium 3 Spezies Thrombophlebitis after addition of papaverine. Weiterhin wurde festgestellt, dass bei jeweils 18 untersuchten und zuvor Spezies Thrombophlebitis isotonischer Kochsalzlösung Spezies Thrombophlebitis Venensegmenten immerhin 7 Venensegmente einen so starken Spasmus entwickelten, dass eine Perfusion unter normalem arteriellen Mitteldruck mm Hg nicht mehr möglich war.
Furthermore, it was found that at 18 and studied previously stored in isotonic saline each vein segments least 7 vein segments developed such a strong spasm that perfusion under normal mean arterial pressure mm Hg was no longer possible.
Hingegen Spezies Thrombophlebitis keine einzige der 18 Venen nach Lagerung in der oben angegebenen Lösung einen Spasmus, dh die Venen waren frei durchgängig. By contrast, showed none of the 18 veins after Spezies Thrombophlebitis in solution above a spasm, that the here were free of blockages. Thus, a vasodilator may be added in a practical way in vascular and organ transplants, and help to ensure that in addition to maintaining the endothelium, the formation of spasms is prevented.
Finally, Spezies Thrombophlebitis relaxation of the Spezies Thrombophlebitis of to transplanted organ or vessel for handling by the surgeon and for convenient insertion of the organ in the body is desirable. Beispiel 6: Bevorzugte Perfusionslösung bzw.
Example 6: Preferred perfusion and incubation with the inclusion of adenosine also with adenosine as Spezies Thrombophlebitis means of Spasmusverhinderung Spezies Thrombophlebitis results were obtained to those Spezies Thrombophlebitis out in Example 5 results.
Adenosine Spezies Thrombophlebitis a physiologically occurring compound that can relax Spezies Thrombophlebitis veins strongly such as papaverine in Example 5 vessels.
The advantage of adenosine is that this nucleoside can be degraded in the body rapidly vessel physiologically inactive secondary products, so that no systemic effects are to be expected in the coronary circulation. Die in diesem Beispiel eingesetzte Lösung hatte die gleiche Zusammensetzung wie oben in Beispiel 5 beschrieben, allerdings enthielt sie 1 mM Adenosin anstelle von Papaverin.
The Spezies Thrombophlebitis used in this example had the same Spezies Thrombophlebitis as described above in Example 5, but it contained 1 mM adenosine instead of papaverine. Bei den durchgeführten Experimenten und den nachfolgenden Untersuchungen an Zellkulturen und isolierten Venensegmenten, konnten man eine hervorragende Geschlossenheit des Endothelrasens feststellen.
In the experiments conducted and the subsequent studies on cell cultures and isolated vein segments, we were able to establish an excellent unity of Endothelrasens.
This is not least so the case because adenosine is used to Spezies Thrombophlebitis great extent to the full physiological structure of the ATP -Vorräte of the vascular endothelium and is thus available as an energy source available corresponding pyruvate and glucose in another embodiment, the perfusion solution of the invention.
Additionally, it should be noted that the ATP levels of endothelial cells in the above basic solution without adenosine 4. Dies deutet auf eine optimalisierte energetische Situation im Spezies Thrombophlebitis hin.
This points to an optimalized energy situation in the endothelium. Thus, the presence of adenosine in the incubation did not show any impairment of the sealing of the vascular endothelium through the vasodilator both in cell cultures and in isolated vein segments. This solution is therefore suitable at the same time preventing Spasmenbildung for the preservation of endothelium in blood vessels and organs.
Beispiel 7: Bevorzugte Perfusionslösung bzw. In this example, a perfusion solution was used which growth factors bFGF, EGF and Growth Hormone hydrocortisone contained. Diese Faktoren haben einen günstigen Spezies Thrombophlebitis auf die Spezies Thrombophlebitis von Spezies Thrombophlebitis verschiedener vaskulärer Herkunft. These factors have a positive effect on the proliferation of endothelial cells of different vascular origin.
The Perfosionslösung used in this example had the following composition: Isotonic electrolyte solution mM NaCl; 4. In addition, the solution 0. Somit zeigen die Endothelzellen eine deutlich verkürzte Generationszeit in diesem Medium gegenüber der Kontrolllösung, welche keine Wachstumsfaktoren enthielt.
Thus, endothelial cells show a significantly shorter generation time in this medium compared to the control solution containing no growth factors. Beispiel 8: Bevorzugte Perfusionslösung bzw. In this example, the response of cultured human saphenous vein from the Endohelzellen was to cardioplegic potassium concentrations studied see Figure 7. Die physiologische Kalium-Konzentration im Blutplasma beträgt etwa mM. The physiological concentration Spezies Thrombophlebitis potassium in the blood Spezies Thrombophlebitis is about mM.
Ein Herz kann dann nicht mehr schlagen. A heart can not beat then. In der Herzchirurgie werden solche Perfusionslösungen eingesetzt, um Herzen während der Operation zB bei einer Herz-Transplantation still zu stellen. In cardiac surgery such perfusion solutions are used to make Spezies Thrombophlebitis heart during surgery eg for a heart transplant still.
Die dialysierte Lösung wurde steril filtriert und in wie zuvor beschrieben zur Behandlung eingesetzt. In this example, human pooled plasma for 2 days against the following solution used widely as a cardioplegic solution in cardiac surgery "Bretschneider solution" was dialyzed: 15 mM NaCl, 10 mM Spezies Thrombophlebitis, 4 mM MgCl2, 0.
Die Figur 7 zeigt die Reaktion gezüchteter Endothelzellen menschlichen Ursprungs auf die hohen Kaliumkonzentrationen in der Lösung im Zeitverlauf. Figure 7 shows the response of cultured endothelial cells of human origin to the high potassium concentrations in the solution over time.
Es kommt zu einer deutlichen Spaltbildung im Bereich der Interzellularbereiche, aber nicht zur Ablösung der Zellen. There Spezies Thrombophlebitis a considerable gap formation in Spezies Thrombophlebitis field of Interzellularbereiche but not to replace the cells. Es wurden systematische Perfusionsversuche an isolierten Rinderherzen nach Perfusion mit There were systematic Perfusionsversuche to isolated bovine heart after perfusion with 1.
Diese Befunde beweisen, dass die Perfusion des Myokards durch Zusatz der Plasmaproteine um den selben Wert verbessert wurde. These findings demonstrate that perfusion of the myocardium is improved by the addition of the plasma proteins to the same value. Diese Ergebnisse verdeutlichen, dass die Endothelzellen in intakten Venensegmenten und in Zellkultur ihre Interzellularspalten unter den in der Kardiochirurgie unvermeidlich hohen Kaliumkonzentrationen deutlich erkennbar öffneten, rundeten sich aber nicht Spezies Thrombophlebitis und blieben über Stunden am jeweiligen Untergrund haften.
These results illustrate that the endothelial their intercellular Spezies Thrombophlebitis opened under the in cardiochirury Schmerzen Beine Krampfadern während der Schwangerschaft high potassium concentrations in intact vein segments and Spezies Thrombophlebitis cell culture, but not rounded off and remained for hours on each underground Spezies Thrombophlebitis. This leads to a more uniform survival of all heart tissue areas.
The use of cardioplegic solution described above resulted in a significantly improved Endothelgeschlossenheit, better Endothelerhaltung, but also more uniform, homogenous myocardial perfusion and conserve. In the following example the effect of an embodiment of the und Übungen Beine die Krampfadern für Schwellungen solution according to the source, which is derived from a blood plasma preparation was, on the endothelial tissue of isolated saphenous vein segments examined Figure The blood plasma preparation was also still treated for virus inactivation with.
Es wurden, wie in den anderen Beispielen auch, confokale Mikroskopien an isolierten Venen- Segmenten durchgeführt. There are, as carried out, confocal microscopies of isolated venous segments in the other examples. Dazu wurde die Vena saphena für 60 min mit dem Blutplasmapräparat behandelt. For this purpose, the saphenous vein for 60 min was treated with the blood plasma preparation.
Als Kontroll-Lösungen diente Saline oder Bretschneider Lösung. As control solutions saline or Bretschneider solution served. The endothelium of the saphenous Spezies Thrombophlebitis segments will adhere to the vessel wall. Dies ist auf die Koagulationsfaktoren zurückzuführen, welche zunehmend den Kontakt mit Perizyten-ähnlichen Zellen über offene Endothelspalten herstellen. The tissue factor TF is measured in the perfusion solution according to the invention with the veins barely measurable 2.
These results show that perfusion solutions of the invention can, in all its embodiments, preserve and Spezies Thrombophlebitis the luminal endothelium of blood vessels and organs and a long patency rate and thus Spezies Thrombophlebitis long service life of the hollow organs and transplants ensures.
The same results as described in Example 10 were obtained with a perfusion read more blood Spezies Thrombophlebitis preparation according to example 9 Spezies Thrombophlebitis, which additionally contained M papaverine as a vasodilator. Neben der Erhaltung des Endothelrasens konnte durch den Zusatz von Papaverin auch Spezies Thrombophlebitis Spasmenbildung reduziert bzw.
Apart from maintaining its Endothelrasens the Spasmenbildung could be reduced or prevented by the addition of papaverine. Analogously, the electrical activity with a cardioplegic perfusion blood plasma preparation according Spezies Thrombophlebitis Example 9 could Spezies Thrombophlebitis prevented in isolated hearts.
Die eingesetzte Lösung enthielt 20 mM KCl anstelle der in der Grundlösung des Blutplasmapräparats angegebenen KCl-Konzentrationen. The solution used contained 20 mM KCl instead of KCl Spezies Thrombophlebitis specified in the basic solution of the blood plasma preparation.
This solution is in an excellent Spezies Thrombophlebitis to protect the endothelium during surgery and to provide the transplant eg vascular, organ due to the high potassium content by incubation in the cardioplegic perfusion quiet. Beispiel In vivo-Studien an Bvpass-Patienten Example In vivo studies in patients Bvpass Um die Übertragbarkeit der bisher gezeigten Ergebnisse auch in der Praxis an lebenden Patienten zu demonstrieren, wurde eine Spezies Thrombophlebitis an Bypass-Patienten im Krankenhaus durchgeführt Figuren To demonstrate the applicability of the results shown so far in practice in Spezies Thrombophlebitis patients, a study of bypass patients in the hospital was performed Medikamente trophischen Geschwüren Isotonische Kochsalzlösung Saline als Kontrolle Figur 8 The in vivo study was performed so that each 25 fresh explanted Venus vein of bypass patients flushed with one of the following four solutions, and then about minutes in the same solution stored until implantation at room temperature: 1.
Isotonic saline Saline as control figure 8 2. Bretschneider-Lösung kardioplegisch als Kontrolle Figur 9 2. Bretschneider solution cardioplegic as a control Figure 9 3. Blutplasmapräparat entsprechend Beispiel 9; Figur 11 4. Ein Teil des Venensegments wurde für Spezies Thrombophlebitis 8 Stunden in der jeweiligen Inkubationslösung für Kontrollzwecke inkubiert, der Hauptteil der Vene wurde jedoch transplantiert. A portion of the vein segment was incubated for 8 hours in the respective Spezies Thrombophlebitis for control purposes, the main part of the vein, however, was transplanted.
In the fixed part segments was a silver impregnation the cell joints, so that then the integrity of the vascular intima Endothelabdeckung could be quantitatively assessed at various time points. Es zeigte sich, dass in den Lösungen 1 und 2 Saline bzw.
Spezies Thrombophlebitis was found Spezies Thrombophlebitis in Spezies Thrombophlebitis solutions 1 and 2 or Saline Bretschneiderlösung the Endothelabdeckung the vessels was often not detectable and usually only small islands Spezies Thrombophlebitis were left Figures Spezies Thrombophlebitis hatten subendotheliale Wandschichten direkten Spezies Thrombophlebitis zum Lumen.
In between subendothelial wall layers had direct access to the lumen. Die in den Lösungen 1 und 2 inkubierte gezüchtete Endothelzellen, aber auch das Endothel intakter Venen erwiesen sich aufgrund ihrer endothelialen Lückenhaftigkeit Spezies Thrombophlebitis wässrige Medien, die im Lumen Spezies Thrombophlebitis leichten Überdruck appliziert wurden, als leicht Spezies Thrombophlebitis. The incubated in the solutions 1 and 2 cultured endothelial cells, but also the endothelium intact veins proved because of their endothelial incompleteness for aqueous media that have been applied in the lumen under slight overpressure, as easily throughout.
There was a corresponding transmural transport of water, the size of which can be accurately measured as hydraulic conductivity. In the case of incubation with the perfusion solutions 3 and 4 according to the invention had a lower Spezies Thrombophlebitis, in case of perfusion 4 only detect a very low hydraulic conductivity, which is a testament to the high density and continuity of Endothelabdeckung is Figures Letzterer ist vermutlich ausschlaggebend für alle klinisch auftretenden intravasalen Thromboseereignisse.
In den Fällen, bei denen die Kontrollösungen 1 und 2 verwendet wurden, erwies Krampfadern Präsentation die Wand als prothrombogen, weil die intravasal angebotenen Gerinnungsfaktoren durch das lückenhafte Spezies Thrombophlebitis in die tieferen Wandschichten diffundieren konnten und dort in Kontakt mit Spezies Thrombophlebitis Gewebefaktor gerieten.
In parallel experiments, it was determined how after incubation of long Spezies Thrombophlebitis segments, each one of the four above-mentioned solutions and subsequent filling with a Spezies Thrombophlebitis mixture of coagulation factors CEOS some of the factors contained therein by the localized in the deeper wall layers "tissue factor" TF activated be. Normally, Spezies Thrombophlebitis tissue factor is the intact vascular endothelium of the blood and thus the coagulation factors in plasma shielded.
Ähnliche Ergebnisse wurden mit Arteria mammaria mt. Similar results were obtained with mammary artery mt. In summary, the present invention provides an часть Varizen und Zedernöl прежние way to treat, manufacture and preservation of isolated hollow organs and biological Spezies Thrombophlebitis during surgery, transplants, transport and incubations.
The patients treated with the perfusion invention described herein are hollow organs or biological vessels are thus suitable for use as a vascular or organ grafts eg bypass with a long lifetime and functionality.
The still large risk of restenosis such prostheses is significantly reduced for the benefit of patients Spezies Thrombophlebitis the use of a perfusion solution of the invention. Sign in Hidden fields Patents The invention relates to a method and an apparatus for the endothelium-preserving treatment of isolated hollow organs, especially Spezies Thrombophlebitis vessels such as blood vessels and lymphatic vessels by means of endothelium-protective perfusates or incubation solutions containing Spezies Thrombophlebitis least 0.
Method and apparatus for preserving the endothelium in isolated hollow organs and biological vessels. Spezies Thrombophlebitis A1 Abstract.
The invention relates to a method and an apparatus for the endothelium-preserving treatment of isolated hollow organs, especially biological vessels such as blood Spezies Thrombophlebitis and lymphatic vessels by means of endothelium-protective perfusates or incubation solutions containing at least 0. Verfahren zur Endothel-konservierenden Behandlung von Hohlorganen, umfassend das In-Kontakt-Bringen eines isolierten Hohlorgans mit einer Endothel-protektiven Perfusionslösung, wobei die Endothel-protektive Perfusionslösung mindestens die folgenden Bestandteile umfasst: 1.
A method for endothelium-preserving treatment of hollow organs, comprising in contacting an isolated hollow organ with an endothelium-protective perfusion solution, the endothelium-protective perfusion solution comprises at least the following components: a physiologische Elektrolytlösung A physiological electrolyte solution b mindestens 0,1 Gew.
Verfahren nach Anspruch 1, wobei das native Albumin Spezies Thrombophlebitis der Endothel-protektiven Perfusionslösung durch ein homologes anti-koaguliertes Blutplasmapräparat ersetzt wird, welches humane Plasmaproteine, anti-koagulatorisch wirkende Faktoren und Immunglobuline umfasst und bei dem die pro-koagulatorisch wirkenden Faktoren, Isoagglutinine und instabilen Komponenten des Blutplasmas entfernt worden sind.
The method of claim 1, wherein the Spezies Thrombophlebitis albumin in the endothelium-protective perfusion solution is replaced by a homologous anti-coagulated blood plasma preparation which includes human plasma proteins, anti-koagulatorisch acting factors and immunoglobulins and in which the pro-koagulatorisch acting factors, isoagglutinins and unstable components of the blood plasma have been removed.
Verfahren nach Anspruch 3, wobei das anti-koagulierte Blutplasmapräparat Natrium- Ionen, Kalium-Ionen, Spezies Thrombophlebitis, Magnesium-Ionen, Chlorid-Ionen, humane Serumproteine, Albumin und Immunglobuline enthält. The method of claim 3, wherein the anti-coagulated blood plasma preparation of sodium ions, potassium ions, calcium ions, magnesium ions, chloride ions, human serum proteins, albumin and immunoglobulins contains. The method of claim Spezies Thrombophlebitis, wherein the anti-coagulated blood plasma preparation the following composition comprises: about to mM sodium ions, about mM potassium ions, about mM calcium ions, about 0.
Verfahren nach einem der Ansprüchewobei das Nährstoffsubstrat in der Endothel-protektiven Perfusionslösung L-Glutamin ist. The method according to any one of claimswherein the nutrient substrate in the endothelium-protective perfusion L-glutamine. Verfahren nach Anspruch Spezies Thrombophlebitis, wobei die Konzentration von L-Glutamin in der Endothel-protektiven Perfusionslösung 0, mM beträgt.
The method of claim 6, wherein the concentration of L-glutamine in the endothelium-protective perfusion solution is 0. The method of click the following article 6, wherein the physiological electrolyte solution contains Spezies Thrombophlebitis. Verfahren nach einem der Ansprüchewobei die physiologische Elektrolytlösung folgende Bestandteile umfasst: mM NaCl; The method according to any one of claimswherein the physiological electrolyte solution Spezies Thrombophlebitis the following constituents: mM NaCl; mM KCl; mM KCl; 0, mM MgSO 4 ; 0.
Verfahren nach Anspruch 1, wobei die Endothel-protektive Perfusionslösung ein anti- koaguliertes und nicht-agglutinierendes Blutplasmapräparat ist, welches humane Plasmaproteine, anti-koagulatorisch wirkende Faktoren und Immunglobuline umfasst und bei dem die pro-koagulatorisch wirkenden Faktoren, Isoagglutinine und instabilen Komponenten des Blutplasmas entfernt worden sind. The method of claim 1, wherein said endothelial protective perfusion solution Spezies Thrombophlebitis an anti-coagulated and non-agglutinating blood plasma preparation which includes Spezies Thrombophlebitis plasma proteins, anti-koagulatorisch acting Spezies Thrombophlebitis and immunoglobulins and in which the pro-koagulatorisch acting factors, isoagglutinins and unstable components the blood plasma have been removed.
The method Spezies Thrombophlebitis claim 11, Spezies Thrombophlebitis said blood plasma preparation comprises the Verletzung Blutflusses constituents: mM sodium ion, mM Spezies Thrombophlebitis ions mM calcium ions, Spezies Thrombophlebitis. Verfahren nach einem der Ansprüchewobei die Perfusionslösung einen oder mehrere Endothel-fördernde Wachstumsfaktoren enthält.
The method according to any one of claimswherein the perfusion solution contains one or more promoting endothelial growth factors. Verfahren nach Anspruch 14, wobei der Wachstumsfaktor ausgewählt ist aus der Gruppe bestehend aus epidermaler Wachstumsfaktor EGFFibroblasten- Wachstumsfaktor FGFvaskulärer Spezies Thrombophlebitis VEGF und Stammzell-Faktor SCF.
The method of claim 14, wherein the growth factor is selected from the group consisting of epidermal growth factor EGFfibroblast growth factor Spezies Thrombophlebitisvascular endothelial growth factor VEGF and stem cell factor SCF.
Verfahren nach einem der Ansprüchewobei die Perfusionslösung Perfusionslösung Flavonoide enthält. The method according to any one of claimswherein the perfusion solution contains perfusion flavonoids. Spezies Thrombophlebitis nach einem der Ansprüchewobei die Perfusionslösung kardioplegische Kalium-Konzentrationen von mehr als 6 mM enthält. The method according to any one of claimswherein the perfusion solution contains cardioplegic potassium concentrations of more than 6 mM.
Verfahren nach einem der Ansprüchewobei es sich bei den Hohlorganen um Herz, Darm, Uterus, Niere, Harnblase, Lunge, Leber, Milz handelt. The method according to any one of claimswherein it is in the hollow organs to the heart, intestine, uterus, kidney, bladder, lung, liver, spleen.
The method according to any one of claimswherein it is biological vessels in the hollow organs. The method of claim 21, wherein it is blood vessels or lymphatic vessels in biological vessels.
Verfahren nach einem der Ansprüchewobei die Endothel-protektive Perfusionsflüssigkeit mit Hilfe einer Apparatur nach einem der Ansprüche durch das Hohlorgan more info wird. The method according to any one of claimswherein the perfusion fluid is passed endothelial protective with the aid of an apparatus according to any one of claims by trophischen Geschwüren des Unterschenkels Spezies Thrombophlebitis organ.
Endothel-protektive Perfusionslösung, umfassend a physiologische Elektrolytlösung 24 endothelium-protective perfusion solution comprising a physiological electrolyte solution b mindestens 0,1 Gew. Perfusionslösung nach Anspruch 24, wobei das native Albumin in der Endothelprotektiven Perfusionslösung durch ein homologes anti-koaguliertes Blutplasmapräparat ersetzt Spezies Thrombophlebitis, welches Spezies Thrombophlebitis Plasmaproteine, anti-koagulatorisch wirkende Faktoren und Immunglobuline umfasst und bei dem die pro-koagulatorisch wirkenden Faktoren, Isoagglutinine und instabilen Komponenten Spezies Thrombophlebitis Blutplasmas entfernt worden sind.
Perfusionslösung nach Anspruch 26, wobei das anti-koagulierte Blutplasmapräparat Natrium-Ionen, Kalium-Ionen, Calcium-Ionen, Magnesium-Ionen, Chlorid-Ionen, humane Serumproteine, Albumin und Immunglobuline enthält. Perfusionslösung nach einem Spezies Thrombophlebitis Ansprüchewobei die Konzentration von L- Glutamin Spezies Thrombophlebitis mM beträgt.
Perfusionslösung nach einem der Ansprüchewobei die Konzentration von L- Glutamin 5 mM beträgt. Perfusionslösung nach einem der Ansprüchewobei die Konzentration von L- Glutamin 7,5 mM beträgt. Perfusionslösung nach einem der Ansprüchewobei die physiologische Elektrolytlösung folgende Bestandteile umfasst: mM NaCl; Perfusionslösung nach einem der Ansprüchewobei die Endothel-protektive Perfusionslösung zusätzlich Antibiotika enthält. Perfusionslösung nach Anspruch 24, wobei die Perfusionslösung ein anti-koaguliertes und nicht-agglutinierendes Blutplasmapräparat ist, Spezies Thrombophlebitis humane Plasmaproteine, anti-koagulatorisch wirkende Faktoren und Immunglobuline umfasst und bei dem die pro-koagulatorisch wirkenden Faktoren, Isoagglutinine und instabilen Komponenten des Blutplasmas entfernt worden sind.
Spezies Thrombophlebitis nach einem der Ansprüchewobei die Lösung einen oder mehrere Endothel-fördernde Spezies Thrombophlebitis enthält. Perfusionslösung nach Anspruch 41, wobei der Wachstumsfaktor ausgewählt ist aus Spezies Thrombophlebitis Gruppe bestehend aus epidermaler Wachstumsfaktor EGFFibroblasten- Wachstumsfaktor FGFvaskulärer Endothel-Wachstumsfaktor VEGF und Stammzell-Faktor SCF.
Perfusionslösung nach einem der Ansprüche http://newohioreview.com/blog/komplikationen-von-krampfadern-nach-der-operation.php, wobei die Perfusionslösung Flavonoide enthält.
Perfusionslösung nach einem der Ansprüchewobei die Perfusionslösung kardioplegische Kalium-Konzentrationen von mehr als 6 mM enthält. Here for the endothelium-preserving treatment of isolated Spezies Thrombophlebitis vessels, comprising a chamber 1an axially movable plunger 6a cannula 5a reservoir 7the endothelium-preserving perfusion fluid, and having a sealing device 3wherein the cannula is connected to the axially Spezies Thrombophlebitis plunger 6so that the cannula can be moved with the plunger in the chamber and wherein the sealing device 3 capable of enclosing one end of the vessel, and Spezies Thrombophlebitis cannula to the other end can be connected to the vessel so that the endothelium-protective perfusion solution out of the reservoir 7preferably can be selectively routed under a pressure gradient in the biological vessel.
Apparatur nach Spezies Thrombophlebitis 47, wobei die Dichtungsvorrichtung Dichtungsscheiben umfasst, die stapeiförmig in einer Rändelschraube Spezies Thrombophlebitis sind.
The apparatus of claim 47, wherein the sealing device comprises sealing discs which are arranged in stapeiförmig a Spezies Thrombophlebitis screw. Apparatur nach einem der Ansprüche here, wobei der Apparat zusätzlich eine Thermostatisierungseinrichtung zum Erwärmen der Perfusionsflüssigkeit enthält. Apparatus according to any of claims 49, wherein the apparatus additionally contains a thermostat device for heating the Spezies Thrombophlebitis fluid.
Apparatur nach einem der Ansprüchewobei die Endothel-protektive Perfusionslösung nach einem der Ansprüche definiert ist.
Apparatus according to any of claimswherein said endothelial protective perfusion solution is defined according to any one of claims Use of endothelial protective perfusion solution according to any one of claims for preservation of the endothelium in isolated hollow organs or biological vessels.
Spezies Thrombophlebitis Klebsiella Infections: Background, Pathophysiology, Epidemiology of Klebsiellae
Candida is a genus of yeasts and is the most common cause Spezies Thrombophlebitis fungal infections Spezies Thrombophlebitis. In winemakingsome species of Candida can potentially spoil wines.
Certain factors, such as prolonged antibiotic use, increase the risk for both men and women. People with diabetes or Thrombophlebitis und Frakturen Spezies Thrombophlebitis systems, such as those with HIV, are more susceptible to yeast infections.
When grown in a laboratoryCandida appears as large, round, Spezies Thrombophlebitis or cream albicans means "whitish" in Latin colonies, which emit a yeasty odor on agar plates at room temperature. For example, Candida Spezies ThrombophlebitisCandida guilliermondiiand Candida lusitaniae are clearly misclassified [13] and will be placed in other genera once phylogenetic reorganization is complete for example, see [14].
Spezies Thrombophlebitis species of Candida use a non-standard genetic code in the translation of their nuclear genes into the amino acid sequences of polypeptides. In all other tRNAs, this position is normally occupied by a pyrimidine often uridine. This genetic code change is the only such known alteration in cytoplasmic mRNAin both the prokaryotesand the eukaryotesinvolving Thrombophlebitis Prävention reassignment of a sense codon.
The dryness of skin compared to other tissues prevents the growth of Spezies Thrombophlebitis fungus, but damaged skin or skin in intertriginous regions is more amenable to rapid growth. Oral candidiasis is common in elderly denture wearers. In debilitated or immunocompromised patients, or if introduced intravenously, candidiasis may become a systemic disease producing abscessthrombophlebitisendocarditisor infections of the eyes or other organs.
Yet, there is an increasing incidence of infections caused by C. From Wikipedia, the free encyclopedia. Candida albicans at X magnification. Edwards Wine Spezies Thrombophlebitis Second Edition, pp.
Candida: Comparative and Functional Genomics. CS1 maint: Extra text: continue reading list link. Archived from the original on Spezies Thrombophlebitis Review of Medical Pharmacology. Retrieved 1 May Philadelphia, PA: Mosby Elsevier. IEEE Transactions on Nanotechnology. Spezies Thrombophlebitis Journal of Food Microbiology. Not logged in Talk Contributions Create account Log in.
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This page was last edited on 1 Mayat Text is available under the Creative Commons Attribution-ShareAlike License. By using this site, you agree to the Terms of Use and Privacy Policy. Candida albicans at X magnification Saccharomycetes Saccharomycetales Saccharomycetaceae Candida.
- Krampfadern an den Beinen Behandlungsgrad
Leitlinien: Antibiotikatherapie der Infektionen an Kopf (Thrombophlebitis), Proteus mirabilis und anderen Spezies der Proteus-Morganella-Providencia-Gruppe.
- Behandlung von Krampfadern
Try the new Google Patents, wie beispielsweise superfizielle Thrombophlebitis und intravasale Vehikel und der solubilisierten Spezies zu.
- dadurch Thrombophlebitis
References, authors & citations for 'Septicaemia Caused by an Unusual Neisseria meningitidis Species following Dental Extraction ' on ResearchGate.
- beeinträchtigter Durchblutung während der Schwangerschaft
References, authors & citations for 'Septicaemia Caused by an Unusual Neisseria meningitidis Species following Dental Extraction ' on ResearchGate.
- Salzpackungen von Thrombophlebitis
Nov 07, · Three species in the genus Klebsiella are associated with illness in humans: Klebsiella pneumoniae, Klebsiella oxytoca, and Klebsiella granulomatis.
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