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 administr ation of adenosine (0.03, 0.3, and 3 mg IC). Hemodynamic and flow meas urements 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, a nd Vessel diameters were measured by a videoelectronic dimension analy zer. In vivo, LAD CF increased fourfold, CFR increased twofold, and co ronary vascular resistance (CVR) decreased fourfold after the administ ration of adenosine. In contrast, LAD CF decreased threefold, CFR decr eased onefold, and CVR increased sixfold 3 minutes after the administr ation of cocaine. Adenosine (3 mg) was repeated 4 minutes after the ad ministration of cocaine, and LAD CF increased 1.4-fold, CVR increased 2.5-fold, and CFR decreased onefold. Thus, adenosine partially reverse d the potent cocaine constrictor effect. In vitro, 10(-9) mol/L cocain e decreased the diameter of the coronary microvessels from 129+/-12 to 127+/-12 mu m, and 10(-4) moL/L cocaine decreased coronary microvesse l diameter to 114+/-15 mu m (P<.05). In conclusion cocaine in vivo dec reases CFR, and consistent with the in vivo effect, cocaine in vitro p roduced constriction of vessels <200 mu m. These results indicate that cocaine can produce profound microvascular spasm. This may contribute to the ischemia/infarction reported in patients who abuse cocaine and who are subsequently found to have normal epicardial coronary arterie s.