Abstract 15697: Cocaine-Induced Ischemia in the Human Coronary Microcirculation: Evidence from Myocardial Contrast Echocardiography
Background: Cocaine commonly causes acute coronary syndrome but the exact mechanism is unknown and thus treatment remains empirical. We used myocardial contrast echocardiography (MCE) to test the hypothesis that cocaine, an indirect sympathomimetic stimulating both vascular α- and cardiac β- adrenergic receptors, causes microvascular ischemia in the human heart by decreasing myocardial capillary perfusion while increasing myocardial oxygen demands.
Methods: Six healthy cocaine-naïve male subjects (median age 38Y) were studied at baseline, 45 min after non-intoxicating low-dose intranasal cocaine (2 mg/kg), and during dobutamine (5 mg/kg i.v.), a β-agonist used as an internal control. Measurements included heart rate (HR), mean arterial pressure (MAP), and left ventricular (LV) work (end-systolic elastance x HR) by 2D echocardiography. MCE perfusion imaging was performed with a continuous infusion of microbubbles and post-destructive data were fit to the equation: y = A(1-e-βt) to quantify functional capillary blood volume (A), flux (flow) rate (β) and perfusion (Aβ). Myocardial oxygen consumption (MVO2) was estimated as: (7.2 x 10-4 x (HR x systolic BP) + 1.42). Microvascular conductance was calculated as perfusion divided by MAP.
Results: Despite an increase (p<0.05) in MAP (+17+3 mmHg), HR (+6 + 3 bpm), LV work (+63+28%), and MV02 (+19+8%), cocaine decreased both microvascular conductance (1.6 + 0.2 to 0.98 + 0.2 a.u./mmHg, p<.05) and capillary volume (A-value 138 + 5 to 113 + 11 a.u., p<0.05) and produced a trend toward decreased myocardial perfusion (-24+18%, p=.08). In contrast, dobutamine (5 mg/kg i.v.) resulted in significant (p<0.05) increases in MV02 (+34 + 9%), microvascular conductance (1.5 + 0.3 to 1.8 + 0.3 a.u./mmHg) and perfusion (44 + 11%) due to increased flux (β-value 0.8 + 0.1 to 1.2 +0.2, p<.05) without capillary volume change (A-value 139 + 8 to 135 + 9).
Conclusions: In humans, cocaine-induced sympathoexcitation acts at the level of the coronary microvessels to cause a mismatch between myocardial oxygen demand and perfusion. Microvascular ischemia from inappropriately reduced functional capillary density constitutes a specific therapeutic target which could improve treatment of cocaine-induced acute coronary syndrome.
- © 2012 by American Heart Association, Inc.