22 December 2010
Prevention of hyperacute xenograft rejection through direct thrombin inhibition with hirudin
Paolo Brenner, Miriam Keller, Andres Beiras-Fernandez, Sunji Uchita, Felix Kur, Eckart Thein, Cosmas Wimmer, Claus Hammer, Michael Schmoeckel, Bruno ReichartAnn Transplant 2010; 15(4): 30-37 :: ID: 881349
Abstract
Background: Hyperacute xenograft rejection (HXR) is characterized by complement activation and intravascular thrombosis. The pathogenesis of HXR is attributed to antibodies binding to α-Gal-epitopes on the endothelial cells (EC) of the xenograft, activating complement and thrombin-mediated coagulation mechanisms. Our aim was to evaluate the influence of thrombin inhibition upon HXR and tissue integrity in an ex-vivo working heart model.
Material/Methods: Eighteen isolated porcine hearts were perfused with human whole blood in a working heart model. The blood was treated with heparin (n=9) in group G-I and with heparin and additionally recombinant hirudin (0.012 mg/ml bolus, afterwards 4.5 µg/ml/h continuously) in group G-II (n=9). The experiments were terminated at end of cardiac output. Histological analysis was performed after the experiments.
Results: Working heart time of G-II was significantly longer (712.0±37.8 vs. 125.0±31.4 min, p<0.01). Heart weight increase in G-II was lower (0.05±0.01 vs. 0.30±0.06%/min, p<0.01). Stroke work index and specific coronary flow improved significantly in G-II after 120 minutes. Histological analysis revealed increased tissue damage and thrombosis phenomena in G-I. Moreover, immunohistochemistry showed increased C3 and C5b-C9 upon EC of G-I.
Conclusions: Direct thrombin inhibition with Hirudin could be a successful strategy in primate xenotransplantation experiments to prevent tissue damage thus improving the graft survival.
Keywords: hyperacute rejection, Thrombin, Xenotransplantation, anticoagulation, hirudin
501 7
In Press
06 Jun 2023 : Original article
A 15-Year Retrospective Study of Supportive Extracorporeal Therapies Including Plasma Exchange and Continuo...Ann Transplant In Press; DOI: 10.12659/AOT.939745
02 Jun 2023 : Original article
Survival analysis of transplant-associated thrombotic microangiopathy under different diagnostic criteria a...Ann Transplant In Press; DOI: 10.12659/AOT.939890
10 May 2023 : Original article
Incidence of Thromboembolic Complications Following Kidney Transplantation with Short and Extended Aspirin ...Ann Transplant In Press; DOI: 10.12659/AOT.939143
Most Viewed Current Articles
24 Aug 2021 : Review article
Normothermic Machine Perfusion (NMP) of the Liver – Current Status and Future PerspectivesDOI :10.12659/AOT.931664
Ann Transplant 2021; 26:e931664
26 Jan 2022 : Review article
Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive ModelsDOI :10.12659/AOT.934924
Ann Transplant 2022; 27:e934924
29 Dec 2021 : Original article
Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...DOI :10.12659/AOT.933588
Ann Transplant 2021; 26:e933588
15 Mar 2022 : Case report
Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...DOI :10.12659/AOT.935860
Ann Transplant 2022; 27:e935860