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Journal Article

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


Troidl,  Kerstin
Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Kleinert, E., Langenmayer, M. C., Reichart, B., Kindermann, J., Griemert, B., Blutke, A., et al. (2016). Ribonuclease (RNase) Prolongs Survival of Grafts in Experimental Heart Transplantation. JOURNAL OF THE AMERICAN HEART ASSOCIATION, 5(5): e003429. doi:10.1161/JAHA.116.003429.

Cite as: https://hdl.handle.net/21.11116/0000-0001-C077-0
Background-Cell 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 Results-Inbred 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 mu g/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 mu g/kg IV every other day, 11.0 days, interquartile range 0.3, versus 8.0 days, interquartile range 0.5, P=0.007). Conclusions-Upon 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.