Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

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 Reichart

Ann 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

Add Comment 0 Comments

Most Viewed Current Articles

15 Aug 2023 : Review article   7,203

Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ Transplantation

DOI :10.12659/AOT.939750

Ann Transplant 2023; 28:e939750

03 Jan 2023 : Original article   7,086

Impact of Autologous Stem Cell Transplantation on Primary Central Nervous System Lymphoma in First-Line and...

DOI :10.12659/AOT.938467

Ann Transplant 2023; 28:e938467

16 May 2023 : Original article   6,914

Breaking Antimicrobial Resistance: High-Dose Amoxicillin with Clavulanic Acid for Urinary Tract Infections ...

DOI :10.12659/AOT.939258

Ann Transplant 2023; 28:e939258

28 May 2024 : Original article   6,394

Effect of Dexmedetomidine Combined with Remifentanil on Emergence Agitation During Awakening from Sevoflura...

DOI :10.12659/AOT.943281

Ann Transplant 2024; 29:e943281

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358