TY - JOUR
AU - Morgan, James, P
AB - Abstract 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 HC1 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 KC1. 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 vasodilatation when these occur in cocaine intoxicated patients. Cardiovascular Research 1993;27:262-268 calcium, cardiac muscle, smooth muscle, excitation-contraction coupling, aequorin, cocaine. This content is only available as a PDF. Author notes The authors express their appreciation to Dr Frederick Schoen and Dr Evan Loh. Division of Cardiac Pathology, Department of Pathology. Brigham and Women's Hospital and the Department of Pathology at Beth Israel Hospital for their help with tissue acquisition and to Jason Kravitz for the careful typing of this manuscript. This work was supported in part by grant DA05171 from the National Institute of Drug Abuse. Bethesda. Maryland, USA. a research career development award to James P Morgan (HL01611) and grant HL31704 from the National Heart, Lung and Blood Institute, Bethesda, Maryland. USA to Kathleen G Morgan. KGM was an established Investigator of the American Heart Association during the period of this study. Copyright © 1993, European Society of Cardiology
TI - Negative inotropic and relaxant effects of cocaine on myopathic human ventricular myocardium and epicardial coronary arteries in vitro
JO - Cardiovascular Research
DO - 10.1093/cvr/27.2.262
DA - 1993-02-01
UR - https://www.deepdyve.com/lp/oxford-university-press/negative-inotropic-and-relaxant-effects-of-cocaine-on-myopathic-human-a80pCwdRqP
SP - 262
EP - 268
VL - 27
IS - 2
DP - DeepDyve
ER -