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 tration 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 ,um, and 10m ol/L cocaine decreased coronary microvessel diameter to 114±15 gm (P<.05). In conclusion, cocaine in vivo decreases CFR, and consistent with the in vivo effect, cocaine in vitro produced constriction of vessels <200 ,um. 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 arteries. (Circ Res. 1994; 74:281-290.) Key Words * cocaine * coronary blood flow * coronary flow reserve * microcirculation tion. In addition, the coronary vascular effects of cocaine were mediated via adrenergic stimulation and modulated by cholinergic blockade.20 We have previously reported that progressive administration of cocaine (1, 3, and 10 mg/kg given at 10-minute intervals) induced transmural myocardial infarction in a Yorkshire pig.21 There was no evidence of epicardial coronary spasm or intravascular thrombosis, but with each cocaine dose, CBF decreased and CVR increased. Therefore, we speculated that cocaine induced microvascular spasm. In support of our findings, Vitullo et a122 documented cocaine-induced microvascular constriction in vessels <60 ,um without epicardial coronary vasoconstriction in isolated rat hearts.The purpose of the present study was to test the hypothesis that cocaine can produce microvascular spasm and, consequently, myocardial infarction. We used Yucatan miniature swine because this variety of pigs has been useful for studying the complex processes of neointimal proliferation, thrombosis, and coronary spasm.23-26 Moreover, Egashira et a127 have shown that Yucatan miniature swine under general anesthesia demonstrate a significant increase in arterial pressure and heart rate in response to large cocaine doses. Our specific aims were (1) to determine the coronary vasodilator reserve before and after the administration of cocaine, (2) to determine the in vivo and in vitro effects of cocaine on the reactivity of epicardial coronary arteries before and 3 months after balloon vascular injury (endothelial denudation of the left circumflex coronary artery [LCX] and angioplasty of the left
