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

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 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). 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. © 2016 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.