Cocaine-Induced Vasoconstriction in the Human Coronary Microcirculation

Abstract

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- β t) to quantify functional capillary blood volume (A), microvascular flow velocity (β), and myocardial perfusion (A × 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.

Cardiovascular consequences of cocaine use

“…Consistent with the known effects of cocaine on the sympathetic nervous system, cardiomyocytes, and vasculature, recent work using myocardial contrast echocardiography clearly demonstrated that cocaine use resulted in a sizeable decrease in myocardial perfusion and decreased myocardial capillary blood volume in otherwise healthy, cocaine-naive young men [31]. Over time, with ongoing cocaine use hypertension, aortic stiffness, left ventricular mass, and other measures of adverse cardiovascular dynamics progressively worsen in otherwise healthy young individuals [32][33][34].…”

“…As described above, the clinical consequences of cocaine use in the short-term include increased myocardial oxygen demand with concomitant decrease in myocardial oxygen supply as well as a demonstrable decrease in myocardial perfusion and decreased myocardial capillary blood volume in otherwise healthy, cocaine-naive young men [31]. Immediately following cocaine use, cocaine-associated chest pain is particularly common and in some may seem ischemic in nature, characterized by pain that is substernal and pressurelike, while in others, the pain seems to have a pleuritic component [10].…”

Acute Effect of Hookah Smoking on the Human Coronary Microcirculation

“…dobutamine in both dogs 23 and young men. 14 Although CO is a direct coronary vasodilator, 12 the mechanism of the increase in myocardial blood flow with acute CO inhalation is mainly capillary recruitment, 24 causing increased myocardial blood volume with unchanged myocardial blood flow velocity—the opposite pattern of microvascular response to what we saw with hookah smoking.…”

“…infusion of lipid-shelled perflutren-containing microbubbles by one experienced sonographer (XT) as previously described, using proved methods to minimize variability. 14,15 Contrast-enhanced 2-dimensional transthoracic echocardiography was performed using a phased-array probe interfaced with an imaging system (iE33; Philips Medical Systems, Andover, Massachusetts). One vial (1.3 ml) of lipid-shell octafluoropropane microbubbles (Definity; Lantheus Medical Imaging, North Billerica, Massachusetts) was diluted to a total volume of 30 ml in normal saline solution and administered intravenously with an infusion pump (Medfusion 3500 Syringe Pump; Smiths Medical ASD Inc, St. Paul, Minnesota) at a rate of 1.0 ml/min.…”

“…In our laboratory, the coefficient of variation is 3% for myocardial A, and 13% for both myocardial β and myocardial perfusion (A·β), documenting test–retest reproducibility. 14 …”