Contractile dysfunction in experimental cardiac allograft rejection: role of the poly (ADP‐ribose) polymerase pathway

Summary Recent studies suggested that the peroxynitrite‐poly (ADP‐ribose) polymerase (PARP) pathway is activated during acute allograft rejection. We investigated whether PARP inhibition improves transplant function during cardiac rejection. Isogeneic Lewis‐to‐Lewis and allogeneic Dark Agouti‐to‐Lewis rat cardiac transplants were studied under treatment with placebo or with the PARP‐inhibitor INO‐1001 (1 mk/kg/day), Functional, biochemical and histological analysis were performed 3 and 5 days after transplantation. After 3 days, baseline left ventricular pressure–volume relationships did not differ between the groups. However, coronary blood flow (4.3 ± 0.5 vs. 2.2 ± 0.2 vs. 4.1 ± 0.3 ml/min/g, P