CARDIAC PROTECTION BY ISCHEMIC PRECONDITIONING IS NOT MEDIATED BY MYOCARDIAL STUNNING

Objective: Previous studies have shown that cardiac protection by isch aemic preconditioning wanes before contractile function recovers; thus stunning is insufficient to cause preconditioning. To test whether re duced contractile effort is necessary for preconditioning induced prot ection, the effect on myocardial infarct size of restoring contractile function with dobutamine was examined in preconditioned and control d ogs. Methods: In two experimental groups (groups P and P+D), precondit ioning was produced by four 5 min occlusions of the left anterior desc ending coronary artery, each separated by 5 min of reperfusion. Contra ctile function was assessed by sonomicrometry 5 min after completion o f the preconditioning protocol. In group P+D, dobutamine (average dose = 5 mug.kg-1.min-1) was then infused intravenously to restore systoli c shortening to baseline. The artery then was reoccluded for 40 min of sustained ischaemia followed by 4 d of reperfusion. Two additional gr oups of non-preconditioned control dogs (groups C and C+D) also underw ent 40 min of coronary occlusion and 4 d of reperfusion. Group C+D rec eived a dobutamine infusion beginning 15 min before and during the 40 min occlusion to match the dobutamine received in group P+D, whereas g roup C received normal saline. Results: Preconditioning caused mild po stischaemic contractile dysfunction (50% decrease in systolic shorteni ng) which was easily reversed by dobutamine treatment. Dobutamine also increased both the rate-pressure product and the left ventricular dP/ dt in both treated groups (C+D and P+D). Histological infarct size was 12.3(SEM 2.0)% of the area at risk in the untreated control group (n= 11), and was reduced to 4.4(l.7)% in the untreated preconditioning gro up (n=8; p<0.05). Dobutamine increased non-preconditioned infarct size (group C+D) to 22.1(3.4)% (n=7; p<0.05). Infarct size in the dobutami ne treated preconditioning group (P+D) was not significantly different from infarct size in group P (n=8), at 6.1(2.5%). Conclusions: In pre conditioned hearts, dobutamine restored postischaemic contractile func tion but did not increase infarct size significantly. Thus reduced con tractile effort is not required for the cardioprotective effect on isc haemic preconditioning.