Effects of cocaine on epicardial coronary artery reactivity in miniature swine after endothelial injury and high cholesterol feeding. In vivo and in vitro analysis.

Abstract

The purpose of this study was to determine the effects of cocaine on vasoreactivity in the swine model. Eight miniature pigs underwent regional endothelial denudation of the left anterior descending coronary artery and were then fed a high cholesterol diet. Cross-sectional area (CSA) of coronary arteries was measured by quantitative angiography. Before denudation, intravenous cocaine (1, 3, and 10 mg/kg) decreased CSA of epicardial vessels by 19-44%. At 3 mo after the denudation, the percent reduction in CSA of the denuded vessels induced by the 10 mg/kg dose was significantly augmented compared to nondenuded vessels (59±5% vs. 48±4%, P < 0.05). Under in vitro conditions where isometric force of isolated ring segments was measured, methoxamine (an a1 agonist) or BHT-920 (an a2 agonist) produced similar degrees of contraction of denuded and control vessels; however, cocaine in concentrations up to 3 x 10-3 M did not produce contraction. These responses were unaffected by removal of the endothelium. Histologically, myointimal thickening was noted at the denuded site. The present study demonstrates an enhanced vasoreactivity of atherosclerotic coronary arteries to cocaine in vivo, the mechanism of which appears to be mediated by endogenous vasoactive substances rather than by a direct action of cocaine on vascular smooth muscle. (J. Clin. Invest. 1991Invest. . 88:1307Invest. -1314

Side Effects of Cocaine Abuse: Multiorgan Toxicity and Pathological Consequences

“…First, cocaine, due to its adrenergic stimulation, causes an increase in heart rate, blood pressure, and LV contractility [129]. Second, documented in several animal studies [98,[130][131][132][133][134][135] is coronary vasoconstriction associated with cocaine use, due to the stimulation of coronary arterial-adrenergic receptors [136,137]. These studies demonstrated that cocaine administered intravenously caused a decrease in coronary artery caliber and decreased coronary blood flow.…”

Intracoronary versus intravenous effects of cocaine on coronary flow and ventricular function.

“…First, in vitro studies have reported that adrenergic blockade can influence the effects of cocaine on coronary vascular tone. 13 Increased adrenergic activity has therefore been proposed as an explanation for the effect of cocaine on coronary tone. Also, in vitro evidence suggests that a direct vasodilatory effect of cocaine is apparent at 10-4 mol/L (30 ,ug/mL) concentrations.…”

Cocaine‐induced microvascular vasoconstriction but differential systemic haemodynamic responses in Yucatan versus Yorkshire varieties of swine

“…Available data in experimental animals suggest that cocaine administration may precipitate myocardial ischaemia either by increasing myocardial oxygen demand, decreasing coronary blood flow, or through a combination of both effects (Hollander & Carter, 1992;Kuhn et al, 1989;Lange et al, 1989). Egashira et al (1991) have shown that cocaine produces a dose-related increase in mean artery pressure (MAP) and heart rate (HR) in miniature swine, whereas we found that cocaine (1, 3 and 10 mg kg-', i.v.) decreases MAP and HR in Yorkshire swine (Nunfiez et al, 1993).…”