Cocaine-Induced Vasoconstriction in the Human Coronary Microcirculation: New Evidence from Myocardial Contrast Echocardiography
Background—Cocaine is a major cause of acute coronary syndrome (ACS), especially in young adults; however, the mechanistic underpinning of cocaine-induced ACS remains limited. Previous studies in animals and in patients undergoing cardiac catheterization suggest that cocaine constricts coronary microvessels, yet direct evidence is lacking.
Methods and Results—We used myocardial contrast echocardiography (MCE) to test the hypothesis that cocaine causes vasoconstriction in the human coronary microcirculation. Measurements were performed at baseline and after a low non-intoxicating dose of intranasal cocaine (2 mg/kg) in 10 healthy cocaine-naïve young men (median age 32 years). Post-destruction time-intensity MCE kinetic data were fit to the equation: y = A(1-e-βt) to quantify functional capillary blood volume (A), microvascular flow velocity (β), and myocardial perfusion (A x β). Heart rate (HR), mean arterial pressure (MAP), and LV work (two-dimensional echocardiography) were measured before and 45 minutes after cocaine. Cocaine increased MAP (+14±2 mmHg; mean ± SE), HR (+8±3 beats/min), and LV work (+50±18 mmHg•mL-1•bpm-1). Despite increasing these determinants of myocardial oxygen demand, myocardial perfusion decreased by 30% (103.7±9.8 to 75.9±10.8 a.u/s, p<0.01) due mainly to decreased capillary blood volume (133.9±5.1 to 111.7±7.7 a.u., p<.05) with no significant change in microvascular flow velocity (0.8±0.1 to 0.7±0.1 a.u.).
Conclusions—In healthy cocaine-naïve young adults, a low-dose cocaine challenge evokes a sizeable decrease in myocardial perfusion. Moreover, the predominant effect is to decrease myocardial capillary blood volume rather than microvascular flow velocity, suggesting a specific action of cocaine to constrict terminal feed arteries.
- Received April 1, 2013.
- Revision received May 17, 2013.
- Accepted June 18, 2013.