EFFECT OF CATECHOLAMINE DEPLETION ON MYOCARDIAL INFARCT SIZE IN DOGS - ROLE OF CATECHOLAMINES IN ISCHEMIC PRECONDITIONING

Objectives: Cardioprotective adaptation to brief periods of ischemia a nd reperfusion is termed ischemic preconditioning (PC). Limitation of infarct size by preconditioning is associated with marked slowing of i schemic metabolism. The cause of metabolic slowing has not been determ ined but may involve either pro- or anti-adrenergic mechanisms. Hypoth etically, adrenergic stimulation could signal the adaptive response. A lternatively, metabolic slowing during the sustained ischemic challeng e could occur through a reduction in beta-adrenergic stimulation. This study was designed to test the role of cardiac norepinephrine (NE) in PC. Methods: The effect of PC on myocardial infarct size was studied in control dogs and dogs depleted of catecholamines by pretreatment wi th reserpine (RES; 0.25 mg/kg i.v.). PC was induced by four cycles of 5 min of ischemia and 5 min of reperfusion. Infarcts were produced by 60 min of ischemia and 3 h of reperfusion. Cardiac NE depletion was ve rified by radioimmunoassay of tissue samples and by absence of hemodyn amic response to a tyramine bolus (1.4 mg/kg) administered at the end of each experiment. Infarct size, expressed as percent of area at risk , was controlled for variation in collateral blood flow using analysis of covariance (ANCOVA). Results: Adjusted mean infarct size was 25.5 +/- 3.2% in untreated controls vs. 19.1 +/- 3.3% in RES-treated contro ls (P = NS). PC limited infarct size in untreated dogs (7.4 +/- 1.8 vs . 25.5 +/- 3.2%; PC vs. control; P < 0.01) but not in RES-treated dogs (15.7 +/- 3.0% vs. 19.1 +/- 3.3%; RES + PC vs. RES; P = NS). Infarct size was larger in dogs with RES + PC than with PC alone, even though there was a trend toward a slight beneficial effect with RES alone. Co nclusions: The cardioprotective effect of ischemic preconditioning can not be explained entirely as an anti-adrenergic effect. On the contrar y, adrenergic receptor stimulation may be required for the full expres sion of ischemic preconditioning in canine myocardium.