COCAINE CARDIOTOXICITY DIFFERS MARKEDLY IN ISOLATED HEARTS OF 2 STRAINS OF RATS EXHIBITING PHENOTYPIC DIFFERENCES IN SENSITIVITY TO SEIZURES

Isolated hearts from two strains of rats bred for sensitivity or resis tance to amygdala kindling that also exhibit, in vivo, differential se nsitivity to the cardiotoxicity of cocaine were studied. The goal was to determine if the differential cardiotoxic sensitivity was due, at l east in part, to intrinsic strain-dependent differences in the heart. The Langendorff preparation was used (n=8 per strain). Hearts were per fused with increasing concentrations of cocaine (5x10(-6), 1x10(-5), 5 x10(-5), 1x10(-4), and 5x10(-4) M) for 5 min with a 5 min washout betw een exposure to successive concentrations. Consistent with in vivo obs ervations, hearts from genetically slow amygdala kindling rats (Slow) required lower cocaine doses to develop cardiac arrhythmias and arrest as compared to the hearts from genetically fast amygdala kindling rat s (Fast). At 5x10(-5)M cocaine arrhythmias occurred in 38% (3/8) Slow and 0% Fast hearts. Five of 8 Slow hearts and none of 8 Fast hearts we re arrested by 10(-4)M cocaine. Arrest in Fast hearts occurred only wi th 5x10(-4)M cocaine. Cocaine constricted coronary arteries (no signif icant difference between strains). On the other hand, coronary arterie s of Slow but not Fast hearts dilated during cocaine washout after per fusion with all but the highest concentration of cocaine. We conclude that factors intrinsic to the heart and coronary artery influence the sensitivity or response of these structures to cocaine.