Nitecapone inhibits myeloperoxidase in vitro and enhances functional performance after 8 h of ischemia in experimental heart transplantation

Nitecapone (NC) has been shown to have beneficial effects on the functional recovery of rat hearts in Langendorff-preparation. The present study was e xecuted to evaluate the effect of NC on preservation of grafts in heart tra nsplantation and the role of NC in the inhibition of granulocyte infiltrati on. Donor hearts were perfused and stored at +4 degrees C for 8 h in either Ringer solution in the control-group (C-group, n = 26) or in NC (50 mu M) added Ringer solution (NC-group, n = 18). The heterotopic heart transplanta tion was performed. The rats in both groups were killed at either 10 min or 60 min after release of the aortic clamp and tissue samples were obtained for antioxidative capacity, myeloperoxidase activity, and lipid peroxidatio n measurements. In vitro studies were performed using sodium azide or nitec apone to inhibit myeloperoxidase (MPO) activity of isolated human leukocyte s, A total of 61% of the grafts began to beat in the KC-group, compared to 46% in the control group. Using an arbitrary scale of functional performanc e, only 33% (4/12) of the grafts were classified as well functioning in the control group, compared to 82% (9/11) in the NC-group (P<0.05). MPO activi ty was equal in both groups after 10 min but significantly lower after 60 m in in the NC-group as compared to the control group (P<0.05). In vitro stud ies demonstrated that NC inhibits 50% of purified MPO activity at a concent ration of 10 mu M. NC did not significantly affect lipid peroxidation or th e preservation of endogenous antioxidants. Since NC inhibited myeloperoxida se both in vitro and in vivo, it seems that the positive effects of NC on g raft preservation may be mediated via the inhibition of granulocyte infiltr ation.