EFFECTS OF COCAINE ON CAROTID VASCULAR REACTIVITY IN SWINE AFTER BALLOON VASCULAR INJURY

Background and Purpose The use of cocaine has been associated with str oke. To evaluate carotid vasospasm as a potential mechanism of cocaine -induced stroke, we studied 12 swine immediately and 10 weeks after an gioplasty. Methods We compared the short- and long-term vasoconstricte r responses of normal and injured arterial segments to nitroglycerin, histamine, and cocaine in vivo by carotid angiography. We also compare d the isometric contractile force responses to different vasoactive su bstances in normal and injured vascular rings in vivo, and we tested t he direct action of cocaine an both arterial segments. Results In in v ivo studies, immediately after angioplasty, luminal diameter in the co ntrol segment decreased by 30% with histamine 30 mu g/kg and by 23% wi th cocaine 10 mg/kg (P < .001). In contrast, neither histamine nor coc aine produced vasoconstriction in the angioplasty segment. Thus, a tra nsient loss of vasoconstriction occurred at the angioplasty site. Ten weeks later, histamine 30 mu g/kg significantly (P < .001) decreased l uminal diameter by 34% in the control and by 33% in the angioplasty se gment; similarly, cocaine 10 mg/kg significantly (P < .001) decreased luminal diameter by 26% in the control and by 34% in the angioplasty s egment. Thus, 10 weeks after angioplasty, the transitory loss of carot id vasoconstriction in response to histamine and cocaine reverted, and a moderate generalized vasoconstriction occurred in both segments wit hout localized vasospasm. In vitro, the maximal isometric tension resp onses to KCI, acetylcholine, histamine, and phenylephrine were similar in vascular rings from normal and angioplasty segments. The median ef fective doses to histamine and phenylephrine were similar. In contrast , cocaine in concentrations from 10(-7) to 10(-3) mol/L failed to prod uce any isometric contraction in vitro. Conclusions Cocaine in vivo pr oduced a generalized carotid vasoconstriction without evidence of loca lized vasospasm; since there was no response to cocaine in vitro, the in vivo effect was most likely mediated by neurohumoral factors rather than by a direct action of cocaine on vascular smooth muscle.