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Original title:
Die Rolle des Stickoxids (NO) in der akuten Abstoßung nach orthotoper Lebertransplantation.
Original subtitle:
Eine experimentelle Studie im Rattenmodell
Translated title:
iNOS inhibition in orthotopic liver transplantation: effects on graft survival and nitric oxide levels
Translated subtitle:
An experimental study in a rat model
Matevosjan, Eduard
Document type:
Fakultät für Medizin
Heidecke, Claus-Dieter (Prof. Dr.)
Neumeier, Dieter (Prof. Dr.); Brauer, Robert (Priv.-Doz. Dr.); Siewert, Jörg Rüdiger (Prof. Dr. Dr. h.c.)
Subject group:
MED Medizin
Lebertransplantation; Immunsuppression; Abstoßung; Stickoxid
Translated keywords:
Liver transplantation; immunsuppression; rejection; nitric oxide
Die Immunmechanismen der Organtransplantatabstoßung sind noch nicht gänzlich geklärt. Es besteht kein Zweifel, daß Stickoxid (NO) eine wesentliche Rolle in der akuten Abstoßung über die inflammatorische Antwort und Apoptose einnimmt. Aminoguanidinhydrochlorid (AGH) ist als potenter Inhibitor der induzierbaren NO-Synthase (iNOS) bekannt. Die Rolle dieses selektiven iNOS-Inhibitors als immunsuppressives Agens wird kontrovers diskutiert. Ziel dieser Studie war es daher, den Effekt von AGH auf das T...    »
Translated abstract:
Introduction: It is generally accepted that nitric oxide (NO) plays a critical role in the acute rejection through inflammatory response and apoptosis. Amminoguanidine hydrochloride (AGH) is known to be a potent inhibitorof the inducible nitric oxide synthase (iNOS). The role of AGH as an immunsuppressant is currently discussed controversially. The purpose of this study therefore was to characterize the effekt of AGH on the graft survival and NO levels following orthotopic rat liver transplantation (ORLT). Methods: Inbred rats underwent orthotopic liver transplantation under ether anesthesia. DA rats served as donors. LEWIS rats as recipients. Untreated allogeneic transplanted rats as well as allogeneic FK506-treated rats (1 mg s.c./kg BW per day) and syngeneic transplanted rats served as control groups. From the 7th preoperative day on throughout the whole course until rejection the recipients were treated orally with AGH (1% in tap water). At different time points postoperatively the animals were sacrificed and tissue samples were taken for H&E staining, immune lebeling and standard clinical chemistry. The concentration of stable NO breakdown products (NO2/NO3) in serum was determined by means of HPLC. Results: Syngeneic transplanted rats and allogeneic FK506-treated rats demonstrated long-term survival (>90 days after livertransplantation). In contrast, allogeneic AGH-treated grafts were rejected an day 11.2 (± 1.8 d). Simular to allogeneic untreated grafts (11.3 ± 1.7 d). NO2/NO3 levels were effectively reduced in the FK506 group and remained at 71.1 µM (± 1.9 µM) simular to those measured in the syngeneic group (88.1 ± 4.1 µM). In the allogeneic untreated group NO2/NO3 increased to 190 µM (± 2.6 µM) on days 5 and 681.8 µM (± 2.6 µM) on day 10. by AGH treatment the NO2/NO3 concentration remained suppressed until day 8 (30.4 ± 3.7 µM). On day 10 it increased slightly to 266.7 µM (± 14.6 µM), yet this is still more than 2,6 times less than the concentration found in allogeneic untreated animals. Conclusion: In the AGH-treated allogeneic recipients there was no significant increase of graft survival despite effective iNOS inhibition. Contrary to former studies by other authors on experimental models of heart and lung transplantation, the results of this study demonstrate that inhibition of the inducible nitric oxide synthase following orthotopic rat liver transplantation is not adequate to protect the graft from acute rejection.
Publication :
Universitätsbibliothek der Technischen Universität München
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