Die Autoren danken Christiane Pahrmann für ihre histologischen Arbeit. Finanzierung Sonja Schrepfer hat ein Forschungsstipendium der Deutschen Forschungsgemeinschaft (DFG) (SCHR992 / 3 1 und SCHR992/4-1) erhalten haben.]

Ratten mit einem Gewicht ca. 250-300g sind von Charles River (Sandhofer Weg 7, D-97633 Sulzfeld) erworben. Transplantationen werden unter Verwendung PVG Ratten als Spender, und ACI Ratten als Empfänger. Ratten sind unter üblichen Bedingungen, gefüttert Standard Rattenfutter und Wasser ad libidum untergebracht. Alle chirurgischen Instrumente sind vor dem Gebrauch sterilisiert. Donor Zubereitung: Anesthetize Ratte mit Isofluran (2,5-3%) mit einer Induktion Kammer. <ol><li> Shave der Bauch-und Brust-Haar und Ort der Ratte auf den Rücken und legen Sie eine Gesichtsmaske über seinen Mund und Nase zu halten die Anästhesie. </li><li> Desinfizieren Sie die Bauch-und Brustbereich weit über Provo-Jod, nächsten Einsatz 80% Ethanol, wiederholen Sie diesen Schritt dreimal. </li><li> Überprüfen Reflexe kneifen die Hinterfüße sicher sein, dass die Ratte ausreichend narkotisiert ist. </li><li> Exsanguinate der Ratte durch die Eröffnung des Bauches und ein Loch in der abdominalen Aorta. </li><li> Öffnen Sie vorsichtig die Brust, um die absteigende Aorta zu finden. </li><li> Präparieren Sie die Aorta vom umgebenden Gewebe wie Fett, Nerven und der Speiseröhre. </li><li> Entnehmen Sie 1.5cm Stück der Aorta mit einem couter, ohne Gewebeschäden der Aorta. </li><li> Versorgen die Aorten-Transplantat gründlich mit kaltem steriler Kochsalzlösung und speichern das Transplantat bei 4 ° C. </li></ol> Empfänger: Anesthetize Ratte mit Isofluran (2,5-3%) mit einer Induktion Kammer. Die Körpertemperatur ist während des chirurgischen Eingriffs beibehalten. <ol><li> Shave Bauchbereich und gelten Augensalbe auf die Augen vor dem Austrocknen während der Narkose zu verhindern. </li><li> Legen Sie die Ratte auf den Rücken und legen Sie eine Gesichtsmaske über seinen Mund und Nase zu halten die Anästhesie. </li><li> Desinfizieren Sie den Bauchbereich mit Provo-Jod, nächsten Einsatz 80% Ethanol, wiederholen Sie diesen Schritt dreimal. </li><li> Überprüfen Reflexe kneifen die Hinterfüße sicher sein, dass die Ratte ausreichend narkotisiert ist. </li><li> Führen Sie eine Mittellinie Bauchschnitt Trennung der Haut und Muskeln in zwei Schritten auf den Bauch zu öffnen. </li><li> Setzen Sie den Darm in einer angewärmten Kochsalzlösung befeuchtet puderfrei Handschuhe. Klappen Sie den Handschuh um den Darm, um den Verlust von Feuchtigkeit zu verhindern. </li><li> Entfernen Sie das Fettgewebe für die Bauchaorta. </li><li> Präparieren Sie die Aorta Form der infrarenalen Region der Bifurkation, vorsichtig, um Schäden an den Zweigen der Gefäße führen. </li><li> Wenn nötig ligieren Zweige der Aorta. </li><li> Zunächst mit einem mikrochirurgischen Klemme an der infrarenalen Teil der Aorta seziert, um den Blutfluss zu stoppen. </li><li> Als nächstes legen Sie eine zweite Klammer in der Nähe der Bifurkation der Aorta. </li><li> Nun, da der Blutfluss gestoppt wird, entfernen Sie ein kurzes Segment der Aorta. </li><li> Nehmen Sie den Spender Aorten-Transplantat, dass in 0,9% steriler Kochsalzlösung wurde auf Eis gehalten, verkürzen sie die angemessene Länge und Position es in die Lücke. </li><li> Verbinden Sie den Spender Aorta an den Empfänger Aorta, Durchführung fortlaufenden Naht mit 8-0 Prolene Naht (Ethicon, Norderstedt, Deutschland). Beginnen Sie mit dem kranialen Ende-zu-End-Anastomose. </li><li> Wenn das distale Ende-zu-End Anastomose beendet ist, öffnen Sie vorsichtig die distale Klemme. </li><li> Wenn es keine Blutungen nach dem Öffnen der distalen Klemme, öffnen Sie vorsichtig die kraniale Klemme. Im Falle von Blutungen an den Nähten, schließen Sie die Klemme wieder, suchen Sie die Blutungen und die Blutung zu stoppen mit einem einzigen Stich. </li><li> Es sollte eine sichtbare Puls am distalen Ende der Aorta werden. </li><li> Nächstes verschieben Sie den Darm wieder in den Bauch. </li><li> Spülen Sie den Bauch mit vorgewärmtem steriler Kochsalzlösung. </li><li> Schließen Sie die Muskelschicht der Bauchwand mit 6-0 Prolene fortlaufenden Nähten (Ethicon, Norderstedt, Deutschland). </li><li> Verwenden Sie 5-0 Prolene (Ethicon, Norderstedt, Deutschland) läuft Nähte auf der Haut zu schließen. </li><li> Während die Ratte immer noch in Narkose, injizieren 4-5mg/kg Carprofen subkutan. </li><li> Um eine ausreichende Analgesie für diese Art von Verfahren wird Metamizol dem Trinkwasser (50 mg Metamizol pro 100ml) für Schmerzmittel für 3 Tage nach der Transplantation aufgenommen. </li></ol>

<ol>
	<li>Deuse, T., Hoyt, G., Koyanagi, T., Robbins, R. C., Schrepfer, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevention+and+Inhibition+But+Not+Reversion+of+Chronic+Allograft+Vasculopathy+by+FK778.">Prevention and Inhibition But Not Reversion of Chronic Allograft Vasculopathy by FK778.</a> Transplantation. 85, 870-877 (2008).</li><li>Mennander, A., Tiisala, S., Halttunen, J., Yilmaz, S., Paavonen, T., Hayry, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+rejection+in+rat+allografts.+An+experimental+model+for+transplant+arteriosclerosis.">Chronic rejection in rat allografts. An experimental model for transplant arteriosclerosis.</a> Arterioscler Thromb Vasc Biol. 11, 671-680 (1991).</li><li>Ono, K., Lindsey, E. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+technique+of+heart+transplantation+in+rats.">Improved technique of heart transplantation in rats.</a> J Thorac Cardiovasc Surg. 57, 225-225 (1969).</li><li>Poston, R. S., Billingham, M., Hoyt, E. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapamycin+reverses+chronic+graft+vascular+disease+in+a+novel+cardiac+allograft+model.">Rapamycin reverses chronic graft vascular disease in a novel cardiac allograft model.</a> Circulation. 100, 67-100 (1999).</li><li>Schrepfer, S., Deuse, T., Koch-Nolte, F., Krieger, T., Haddad, M., Schäfer, H., Pelletier, M. P., Robbins, R. C., Reichenspurner, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=FK778+in+Experimental+Xenotransplantation:+A+Detailed+Analysis+of+Drug+Efficacy.">FK778 in Experimental Xenotransplantation: A Detailed Analysis of Drug Efficacy.</a> J Heart Lung Transplant. 26, 70-77 (2007).</li></ol>

Aus mehreren Gründen fanden wir den orthotopen Aorten-Transplantation Modell eine genauere Möglichkeit, die Entwicklung der TVP im Vergleich zu den heterotopen Herztransplantation Modell zu untersuchen: In Bezug auf die chirurgische Technik, verkörpert die Aorten-Transplantation Modell eine leicht praktikable Methode, erfordert allein die Erfüllung der End-to-End-Anastomose, während die heterotope Herztransplantation Modell kann als ein komplexer und fehleranfälliger Herausforderung für den Chirurgen s Fä...

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<td>Surgical microscope (magnification 25x)</td>
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<td>ice cold 0.9% saline</td>
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<td>prewarmed 0.9% sterile saleine</td>
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orthotopic aortic transplantation: a rat model to study the development of chronic vasculopathy

Forschung Modelle der chronischen Abstoßung sind unerlässlich, um pathobiologischen und pathophysiologische Prozesse bei der Entwicklung der Transplantatvaskulopathie (TVP) zu untersuchen. Die am häufigsten verwendete Tiermodell für Herz-Kreislauf chronische Abstoßung Studien ist die heterotope Herztransplantation Modell in Labornagern durchgeführt. Dieses Modell wird häufig in Experimenten verwendet werden, da Ono und Lindsey (3) veröffentlicht ihre Technik. Zur Analyse der Ergebnisse in die Blutgefäße, das Herz zu geschnitten und alle Schiffe müssen gemessen werden. Eine andere Methode, um chronische Abstoßung in der kardiovaskulären Fragestellungen zu untersuchen ist die Aorta Transplantation Modell (1, 2). In der orthotopen Transplantation Aorten-Modell können die Aorta leicht histologisch untersucht werden (2). Die PVG-to-ACI-Modell ist besonders nützlich für CAV-Studien, da akute vaskuläre Abstoßung ist keine wichtigen verwirrenden Faktor und Cyclosporin A (CsA)-Behandlung verhindert nicht, dass die Entwicklung der CAV, ähnlich dem, was wir in der klinischen Umgebung zu finden (4 ). A7-Tage-Frist von CsA ist in diesem Modell erforderlich, um akute Abstoßung zu verhindern und um das langfristige Überleben mit der Entwicklung des TVP zu erreichen. Dieses Modell kann auch zur akuten zellulären Abstoßung und Medien Nekrose in xenogenen Modellen (5) zu untersuchen.

Watch this Scientific Journal Video about Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy at JoVE.com

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Dieses Video zeigt die orthotopen Aorten-Transplantat-Modell als ein einfaches Modell für die Entwicklung der Transplantatvaskulopathie (TVP) in Ratten zu untersuchen.

Orthotopen Aorten-Transplantation: Ein Rattenmodell die Entwicklung von chronischen Vaskulopathie Study

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

orthotopic-aortic-transplantation-rat-model-to-study-development

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12.0K Aufrufe.  University Hospital Hamburg. Dieses Video zeigt die orthotopen Aorten-Transplantat-Modell als ein einfaches Modell für die Entwicklung der Transplantatvaskulopathie (TVP) in Ratten zu untersuchen.

Serie: Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Human Internal Mammary Artery (IMA) Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis

Preclinical in vivo research models to investigate pathobiological and pathophysiological processes in the development of intimal hyperplasia after vessel stenting are crucial for translational approaches1,2.
The commonly used animal models include mice, rats, rabbits, and pigs3-5. However, the translation of these models into clinical settings remains difficult, since those biological processes are already studied in animal vessels but never performed before in human research models6,7. In this video we demonstrate a new humanized model to overcome this translational gap. The shown procedure is reproducible, easy, and fast to perform and is suitable to study the development of intimal hyperplasia and the applicability of diverse stents.
This video shows how to perform the stent technique in human vessels followed by transplantation into immunodeficient rats, and identifies the origin of proliferating cells as human.

Human Internal Mammary Artery IMA Transplantation and Stenting: A Human Model to Study the Development of In-Stent Restenosis

This video shows a model to study the development of intimal hyperplasia after stent deployment using a human vessel (IMA) in an immunodeficient rat model.

Menschliche Arteria mammaria interna (IMA) Transplantation und Stenting: A Human Model um die Entwicklung von In-Stent Restenose Studie

Preclinical in vivo research models to investigate pathobiological and pathophysiological processes in the development of intimal hyperplasia after vessel ...

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Medizin

Development of Obliterative Bronchiolitis in a Murine Model of Orthotopic Lung Transplantation

Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 1. Currently, this method is well accepted and standardized not only for the study of allo-rejection but also between syngeneic strains for examining mechanisms of ischemia-reperfusion injury after lung transplantation. Although the application of the rat and other large animal model 2 contributed significantly to the elucidation of these studies, the scope of those investigations is limited by the scarcity of knockout and transgenic rats. Due to no effective therapies for obliterative bronchiolitis, the leading cause of death in lung transplant patients, there has been an intensive search for pre-clinical models that replicate obliterative bronchiolitis. The tracheal allograft model is the most widely used and may reproduce some of the histopathologic features of obliterative bronchiolitis 3. However, the lack of an intact vasculature with no connection to the recipient's conducting airways, and incomplete pathologic features of obliterative bronchiolitis limit the utility of this model 4. Unlike transplantation of other solid organs, vascularized mouse lung transplants have only recently been reported by Okazaki and colleagues for the first time in 2007 5. Applying the basic principles of the rat lung transplant, our lab initiated the obliterative bronchiolitis model using minor histoincompatible antigen murine orthotopic single-left lung transplants which allows the further study of obliterative bronchiolitis immunopathogenesis6.

Obliterative bronchiolitis is the key impediment to the long-term survival of lung transplant recipients and the lack of a robust preclinical model precludes examining obliterative bronchiolitis immunopathogenesis. Unlike other solid organ transplants, vascularized mouse lung transplantation has only recently been developed. Here we show our independently developed obliterative bronchiolitis model after murine orthotopic single-lung transplantation.

Entwicklung einer Bronchiolitis obliterans in einem Mausmodell der orthotopen Lungentransplantation

Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 1. Currently, this method is well accepted and ...

Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. This is largely true, but there are a number of important principles that can reduce the difficulty of these procedures and enhance reproducibility. Orthotopic aortic transplantation is an excellent procedure in which to learn these principles because it involves only two end-to-end anastomoses, but requires good suturing technique and handling of the vessels for consistent success. This procedure begins with the procurement of a length of abdominal aorta from a donor animal, followed by division of the native aorta in the recipient. The procured aorta is then placed between the divided ends of the recipient aorta and sutured into place using end-to-end anastomoses. To accomplish this objective successfully requires a high degree of concentration, good tools, a steady hand, and an appreciation of how easily the vasculature of a mouse can be damaged, resulting in thrombosis. Learning these important principles is what occupies most of the beginner's time when learning microsurgery in small rodents. Throughout this protocol, we refer to these important points. This model can be used to study vascular disease in a variety of different experimental systems1-8. In the context shown here, it is most often used for the study of post-transplant vascular disease, a common long-term complication of solid organ transplantation in which intimal hyperplasia occurs within the allograft. The primary advantage of the model is that it facilitates quantitative morphometric analyses and the transplanted vessel lies contiguous to the endogenous vessel, which can serve as an additional control9. The technique shown here is most often used for mice weighing 18-25 grams. We have accumulated most of our experience using the C57BL/6J, BALB/cJ, and C3H/HeJ strains.

We describe a technique in which a section of the abdominal aorta from a mouse is transplanted orthotopically to just below the renal arteries in an allogeneic or syngeneic recipient. This technique can be useful in studies in which transplantation of large arteries of uniform size is deemed advantageous.

Orthotopen Aortic Transplantation in Mäuse für das Studium der Vascular Disease

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. ...

Surgical Procedures for a Rat Model of Partial Orthotopic Liver Transplantation with Hepatic Arterial Reconstruction

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as studies on graft preservation and ischemia-reperfusion injury 1,2, immunological responses 3,4, hemodynamics 5,6, and small-for-size syndrome 7. The rat OLT is among the most difficult animal models in experimental surgery and demands advanced microsurgical skills that take a long time to learn. Consequently, the use of this model has been limited. Since the reliability and reproducibility of results are key components of the experiments in which such complex animal models are used, it is essential for surgeons who are involved in rat OLT to be trained in well-standardized and sophisticated procedures for this model.
While various techniques and modifications of OLT in rats have been reported 8 since the first model was described by Lee et al. 9 in 1973, the elimination of the hepatic arterial reconstruction 10 and the introduction of the cuff anastomosis technique by Kamada et al. 11 were a major advancement in this model, because they simplified the reconstruction procedures to a great degree. In the model by Kamada et al., the hepatic rearterialization was also eliminated. Since rats could survive without hepatic arterial flow after liver transplantation, there was considerable controversy over the value of hepatic arterialization. However, the physiological superiority of the arterialized model has been increasingly acknowledged, especially in terms of preserving the bile duct system 8,12 and the liver integrity 8,13,14.
In this article, we present detailed surgical procedures for a rat model of OLT with hepatic arterial reconstruction using a 50% partial graft after ex vivo liver resection. The reconstruction procedures for each vessel and the bile duct are performed by the following methods: a 7-0 polypropylene continuous suture for the supra- and infrahepatic vena cava; a cuff technique for the portal vein; and a stent technique for the hepatic artery and the bile duct.

Orthotopic liver transplantation in rats is an indispensable experimental model for biomedical research. Here we present our surgical procedures for orthotopic rat liver transplantation with hepatic arterial reconstruction using a 50% partial graft.

Chirurgische Verfahren für eine Ratte Modell Teilweise Lebertransplantation mit arteriellen Rekonstruktion

Orthotopic liver transplantation (OLT) in rats using a whole or partial graft is an indispensable experimental model for transplantation research, such as ...

A Model of Chronic Nutrient Infusion in the Rat

Chronic exposure to excessive levels of nutrients is postulated to affect the function of several organs and tissues and to contribute to the development of the many complications associated with obesity and the metabolic syndrome, including type 2 diabetes. To study the mechanisms by which excessive levels of glucose and fatty acids affect the pancreatic beta-cell and the secretion of insulin, we have established a chronic nutrient infusion model in the rat. The procedure consists of catheterizing the right jugular vein and left carotid artery under general anesthesia; allowing a 7-day recuperation period; connecting the catheters to the pumps using a swivel and counterweight system that enables the animal to move freely in the cage; and infusing glucose and/or Intralipid (a soybean oil emulsion which generates a mixture of approximately 80% unsaturated/20% saturated fatty acids when infused with heparin) for 72 hr. This model offers several advantages, including the possibility to finely modulate the target levels of circulating glucose and fatty acids; the option to co-infuse pharmacological compounds; and the relatively short time frame as opposed to dietary models. It can be used to examine the mechanisms of nutrient-induced dysfunction in a variety of organs and to test the effectiveness of drugs in this context.

A protocol for chronic infusions of glucose and Intralipid in rats is described. This model can be used to study the impact of nutrient excess on organ function and physiological parameters.

Ein Modell der chronischen Nährstoff Infusion in der Ratte

Chronic exposure to excessive levels of nutrients is postulated to  affect the function of several organs and tissues and to contribute to the  ...

Murine Corneal Transplantation: A Model to Study the Most Common Form of Solid Organ Transplantation

Corneal transplantation is the most common form of organ transplantation in the United States with between 45,000 and 55,000 procedures performed each year. While several animal models exist for this procedure and mice are the species that is most commonly used. The reasons for using mice are the relative cost of using this species, the existence of many genetically defined strains that allow for the study of immune responses, and the existence of an extensive array of reagents that can be used to further define responses in this species. This model has been used to define factors in the cornea that are responsible for the relative immune privilege status of this tissue that enables corneal allografts to survive acute rejection in the absence of immunosuppressive therapy. It has also been used to define those factors that are most important in rejection of such allografts. Consequently, much of what we know concerning mechanisms of both corneal allograft acceptance and rejection are due to studies using a murine model of corneal transplantation. In addition to describing a model for acute corneal allograft rejection, we also present for the first time a model of late-term corneal allograft rejection.

Mice have been used as a model for studying many forms of transplantation, including corneal transplantation. We describe in this report a murine model for both acute and late-term corneal transplantation.

Murine Hornhauttransplantation: Ein Modell, das die häufigste Form der Organtransplantation Studieren

Corneal transplantation is the most common form of organ transplantation in the United States with between 45,000 and 55,000 procedures performed each ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

Messung der isometrischen Kontraktilität der Maus mesenterialen Arterie mit Draht Myographie

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart failure. Multiple small-animal models of heart transplantation have been used to study the acute and long-term effects of novel therapies. However, few are tested and demonstrated success in clinical trials. It is of critical importance to evaluate new therapies in a clinically relevant large-animal model for efficient and reliable translation of basic studies&#39;&#160;findings. Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and previously used to investigate novel cardioprotective strategies. This procedure focuses on acute ischemia-reperfusion injury and is a reliable method to investigate novel interventions which have been tested and validated in smaller experimental models, such as the murine model. We demonstrate its usefulness in assessing cardiac performance during the early post-transplantation period and other potential possibilities enabled by the model.

Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and utilized to investigate novel cardioprotective strategies.

Ein präklinisches Porcine-Modell der orthotopischen Herztransplantation

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart ...

Orthotopic Rat Kidney Transplantation: A Novel and Simplified Surgical Approach

Kidney transplantation offers increased survival rates and improved quality of life for patients with end-stage renal disease, as compared to any type of renal replacement therapy. Over the past few decades, the rat kidney transplantation model has been used to study the immunological phenomena of rejection and tolerance. This model has become an indispensable tool to test new immunomodulatory pharmaceuticals and regimens prior to proceeding with expensive preclinical large animal studies.
This protocol provides a detailed overview of how to reliably perform orthotopic kidney transplantation in rats. This protocol includes three distinctive steps that increase the probability of success: perfusion of the donor kidney by flushing through the portal vein and the use of a cuff system to anastomose the renal veins and ureters, thereby decreasing cold and warm ischemia times. Using this technique, we have achieved survival rates beyond 6 months with normal serum creatinine in animals with syngeneic or tolerant kidney transplants. Depending on the aim of the study, this model can be modified by pre- or posttransplant treatments to study the acute, chronic, cellular, or antibody-mediated rejection. It is a reproducible, reliable, and cost-effective animal model to study different aspects of kidney transplantation.

The purpose of this manuscript and protocol is to explain and demonstrate in detail the surgical procedure of orthotopic kidney transplantation in rats. This method is simplified to achieve the correct perfusion of the donor kidney and shorten the reperfusion time by using the venous and ureteral cuff anastomosis technique.

Orthotopic Rat Nierentransplantation: Ein neuartierter und vereinfachter chirurgischer Ansatz

Kidney transplantation offers increased survival rates and improved quality of life for patients with end-stage renal disease, as compared to any type of ...

Reduced Complications after Arterial Reconnection in a Rat Model of Orthotopic Liver Transplantation

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation of human liver transplantation due to the absence of arterial reconnection. Described here is a modified transplantation procedure that includes the incorporation of hepatic artery (HA) reconnection, leading to a marked improvement in transplant outcomes. With a mean anhepatic time of 12 min and 14 s, HA reconnection results in improved perfusion of the transplanted liver and an increase in long-term recipient survival from 37.5% to 88.2%. This protocol includes the use of 3D-printed cuffs and holders to connect the portal vein and infrahepatic inferior vena cava. It can be implemented for studying multiple aspects of liver transplantation, from immune response and infection to technical aspects of the procedure. By incorporating a simple and practical method for arterial reconnection using a microvascular technique, this modified rat OLT protocol closely mimics aspects of human liver transplantation and will serve as a valuable and clinically relevant research model.

The goal of this study is to modify the rat orthotopic liver transplant model to better represent human liver transplantation and improve recipient survival. The presented method reestablishes hepatic arterial inflow by connecting the donor liver&#39;s common hepatic artery to the recipient liver&#39;s proper hepatic artery.

Reduzierte Komplikationen nach arterieller Wiederverbindung in einem Rattenmodell der orthotopischen Lebertransplantation

The rat orthotopic liver transplantation (OLT) model is a powerful tool to study acute and chronic rejection. However, it is not a complete representation ...