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

Cynthia L. Perreault, Nancy L. Hague, Kathleen G. Morgan, Paul D. Allen, James P. Morgan

Research output: Contribution to journalArticle

22 Scopus citations

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 (10-610-3 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.

Original languageEnglish (US)
Pages (from-to)262-268
Number of pages7
JournalCardiovascular Research
Volume27
Issue number2
StatePublished - 1993
Externally publishedYes

    Fingerprint

Keywords

  • Aequorin
  • Calcium
  • Cardiac muscle
  • Cocaine
  • Excitation-contraction coupling
  • Smooth muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology

Cite this

Perreault, C. L., Hague, N. L., Morgan, K. G., Allen, P. D., & Morgan, J. P. (1993). Negative inotropic and relaxant effects of cocaine on myopathic human ventricular myocardium and epicardial coronary arteries in vitro. Cardiovascular Research, 27(2), 262-268.