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

Kensuke Egashira, Frank S. Pipers, James P. Morgan

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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 α1 agonist) or BHT-920 (an α2 agonist) produced similar degrees of contraction of denuded and control vessels; however, cocaine in concentrations up to 3 × 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.

Original languageEnglish
Pages (from-to)1307-1314
Number of pages8
JournalJournal of Clinical Investigation
Volume88
Issue number4
Publication statusPublished - 1991
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Medicine

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