Negative inotropic and relaxant effects of cocaine on myopathic human ventricular myocardium and epicardial coronary arteries in vitro.

OBJECTIVE

Cocaine produces both vascular and myocardial effects that can lead to serious cardiovascular complications in man. Tissue catecholamine stores are known to be depleted in the advanced stages of heart failure. The effects of cocaine on cardiac and coronary smooth muscle isolated from patients with end stage heart failure was tested in order to evaluate the direct actions of this drug on human tissue.

METHODS

Effects of cocaine HCl were studied on cardiac ventricular trabeculae carneae and epicardial coronary artery segments obtained at heart transplantation from patients with end stage heart failure. Muscles were placed in organ baths under physiological conditions for recording isometric tension; a subset of muscles was loaded intracellularly with the bioluminescent calcium indicator, aequorin. Cardiac muscles were stimulated with threshold pulses delivered via a punctate electrode at 0.33 Hz. Coronary segments were studied under basal conditions and after contraction with 60 mM KCl.

RESULTS

In both cardiac muscle and vascular smooth muscle preparations, cocaine (10(-6)-10(-3) M) produced dose related negative inotropic and relaxant effects, respectively; positive inotropic actions and vasoconstriction were not seen. In cardiac muscle, the negative inotropic actions were associated with a simultaneous decrease in peak intracellular calcium levels. In contrast, cocaine induced relaxation of potassium contracted vascular smooth muscle was not associated with a fall in peak intracellular calcium levels, a result consistent with decreased myofilament calcium responsiveness.

CONCLUSIONS

These results indicate that the depressant effects of cocaine on cardiac versus vascular smooth muscle occur by different mechanisms and suggest the need for specific therapeutic approaches to managing cardiac depression versus vasodilation when these occur in cocaine intoxicated patients.