Cocaine-Induced Microvascular Spasm in Yucatan Miniature Swine: In Vivo and In Vitro Evidence of Spasm

The purpose of the present study was to determine the maximal coronary flow reserve (CFR) before and after the administration of successive cocaine doses (0.1,0.5,3, and 7 mg/kg IV) for 2 minutes at 10-minute intervals in eight miniature swine. CFR was assessed by the administration of adenosine (0....

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Bibliographic Details
Published in:Circulation research 1994-02, Vol.74 (2), p.281-290
Main Authors: Núñez, Boris D, Miao, Lin, Wang, Yudi, Núñez, Maria M, Sellke, Frank W, Ross, James N, Susulic, Vojkan, Paik, George Y, Carrozza, Joseph P, Morgan, James P
Format: Article
Language:English
Subjects:
Adenosine - pharmacology
Animals
Biological and medical sciences
Cocaine - pharmacology
Coronary Circulation - drug effects
Coronary Vasospasm - chemically induced
Coronary Vasospasm - pathology
Coronary Vasospasm - physiopathology
Coronary Vessels - drug effects
Coronary Vessels - pathology
Dose-Response Relationship, Drug
Drug addictions
Female
Hemodynamics - drug effects
In Vitro Techniques
Male
Medical sciences
Microcirculation
Pericardium
Swine
Swine, Miniature
Toxicology
Vasodilation
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Summary:The purpose of the present study was to determine the maximal coronary flow reserve (CFR) before and after the administration of successive cocaine doses (0.1,0.5,3, and 7 mg/kg IV) for 2 minutes at 10-minute intervals in eight miniature swine. CFR was assessed by the administration of adenosine (0.03, 0.3, and 3 mg IC). Hemodynamic and flow measurements were performed 3 minutes after each dose. Coronary flow (CF) was measured with a Doppler-tipped wire in the proximal left anterior descending coronary artery (LAD). Also, microvessels were dissected, and vessel diameters were measured by a videoelectronic dimension analyzer. In vivo, LAD CF increased fourfold, CFR increased twofold, and coronary vascular resistance (CVR) decreased fourfold after the administration of adenosine. In contrast, LAD CF decreased threefold, CFR decreased onefold, and CVR increased sixfold 3 minutes after the administration of cocaine. Adenosine (3 mg) was repeated 4 minutes after the administration of cocaine, and LAD CF increased 1.4-fold, CVR increased 2.5-fold, and CFR decreased onefold. Thus, adenosine partially reversed the potent cocaine constrictor effect. In vitro, 10 mol/L cocaine decreased the diameter of the coronary microvessels from 129±12 to 127±12 μm, and 10 mol/L cocaine decreased coronary microvessel diameter to 114±15 μm (P
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.74.2.281