CP-060S, A NOVEL CARDIOPROTECTIVE DRUG, LIMITS MYOCARDIAL INFARCT SIZE IN ANESTHETIZED DOGS

The myocardial infarct size (IS)-limiting effect of CP-060S, a novel c ardioprotective drug that prevents Na+-, Ca2+-overload and has Ca2+ ch annel-blocking activity, was compared with that of diltiazem, a pure C a2+ antagonist, to determine whether the prevention of Na+, Ca2+-overl oad contributes to this IS-limiting effect. Dogs were subjected to 90 min of left circumflex coronary artery (LCx) occlusion followed by 5 h of reperfusion. Either CP-060S (300 mu g/kg) or diltiazem (600 mu g/k g) was administered intravenously 20 min before the occlusion. CP-060S significantly limited IS compared with that of vehicle (percentage of the area at risk: vehicle, 50.64 +/- 6.08%; CP-060S, 21.13 +/- 3.75%; p < 0.01 vs. vehicle). Although diltiazem exerted a significant decre ase in rate-pressure product (RPP; an index of myocardial oxygen consu mption) during occlusion equal to that of CP-060S, diltiazem did not s ignificantly reduce IS (33.90 +/- 4.30%). Regional myocardial blood fl ow (RBF) was not significantly different between any of the groups. Th erefore the IS limiting effect of CP-060S cannot be explained in terms of changes in RPP or RBE Thus the IS limitation induced by CP-060S is probably the consequence of a direct cardioprotective effect on myocy tes. The prevention of Na+-, Ca2+-overload may be the primary reason f or this IS-limiting effect.