Ribonuclease (RNase) Prolongs Survival of Grafts in Experimental Heart Transplantation

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Fatih Noyan¹  Silvia Fischer²  Barbara Griemert²  Klaus T. Preissner²  Martin C. Langenmayer³  Ruediger Wanke³  Andreas Blutke³  Kerstin Troidl⁴  Sonja Guethoff⁵  Eike Kleinert⁵  Jan‐Michael Abicht⁵  Bruno Reichart⁵  Jana Kindermann⁵  Tobias Grantzow⁵  Tanja Mayr⁵  Elisabeth Deindl⁵ 

[1] Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany;Institute of Biochemistry, Medical School, Justus‐Liebig‐Universität, Giessen, Germany;Institute of Veterinary Pathology at the Centre for Clinical Veterinary Medicine, Ludwig‐Maximilians‐Universität München, Germany;Max‐Planck‐Institute for Heart and Lung Research, Bad Nauheim, Germany;Walter Brendel Centre of Experimental Medicine, Ludwig‐Maximilians‐Universität München, Germany;

关键词: edema;    extracellular RNA;    ischemia/reperfusion injury;    ribonuclease;    transplantation;   

DOI  :  10.1161/JAHA.116.003429

来源: DOAJ

【 摘 要 】

BackgroundCell damage, tissue and vascular injury are associated with the exposure and release of intracellular components such as RNA, which promote inflammatory reactions and thrombosis. Based on the counteracting anti‐inflammatory and cardioprotective functions of ribonuclease A (RNase A) in this context, its role in an experimental model of heart transplantation in rats was studied. Methods and ResultsInbred BN/OrlRj rat cardiac allografts were heterotopically transplanted into inbred LEW/OrlRj rats. Recipients were intravenously treated every other day with saline or bovine pancreatic RNase A (50 μg/kg). Toxic side effects were not found (macroscopically and histologically). Heart tissue flow cytometry and quantitative morphological analyses of explanted hearts at postoperative day 1 or postoperative day 4 showed reduced leukocyte infiltration, edema, and thrombus formation in RNase A‐treated rats. In allogeneic mixed lymphocyte reactions, RNase A decreased the proliferation of effector T cells. RNase A treatment of rats resulted in prolonged median graft survival up to 10.5 days (interquartile range 1.8) compared to 6.5 days (interquartile range 1.0) in saline treatment (P=0.001). Treatment of rats with a new generated (recombinant) human pancreatic RNase 1 prolonged median graft survival similarly, unlike treatment with (recombinant) inactive human RNase 1 (each 50 μg/kg IV every other day, 11.0 days, interquartile range 0.3, versus 8.0 days, interquartile range 0.5, P=0.007). ConclusionsUpon heart transplantation, RNase administration appears to present a promising and safe drug to counteract ischemia/reperfusion injury and graft rejection. Furthermore, RNase treatment may be considered in situations of critical reperfusion after percutaneous coronary interventions or in cardiac surgery using the heart–lung machine.

【 授权许可】

Unknown