BENEFICIAL-EFFECTS OF H290/51, A NEW LIPID-PEROXIDATION INHIBITOR, ON FUNCTIONAL RECOVERY AFTER ISCHEMIA AND REPERFUSION IN ISOLATED COLD-ARRESTED RAT HEARTS

Lipid peroxidation is one of the major mechanisms involved in free radical-mediated postischemic myocardial injury. Ln the present study, a newly synthetized lipid peroxidation inhibitor H290/51 [cis-7metyl-9-methoxy-5,5a,b,10b-tetrahydroindeno(2,1-6 indole)] was evaluated for its effects on myocardial functional recovery during reperfusion after 30-min global ischemia in isolated cold-arrested rat hearts. Administration of 200 and 800 nM H290/51 at initiation of global ischemia markedly improved the functional recovery, whereas 50 nM H290/51 had no significant effects. The percent recovery of cardiac output (CO), left ventricular developed pressure (LVDP), and LVdP/dt(max) at the end of the 30-min reperfusion period in the working mode was much higher in the groups receiving 200 and 800 nM H290/51 than that in vehicle group (CO 73 +/- 5 and 60 +/- 5 vs. 23 +/- 7%; LVDP 79 +/- 5 and 73 +/- 8 vs. 43 +/- 10%; LV dP/dt(max) 78 +/- 5 and 69 +/- 4 vs. 45 +/- 10%). The indenoindole compound H290/51 51 reduced ischemia/reperfusion-induced cardiac dysfunction.