Intracoronary versus intravenous effects of cocaine on coronary flow and ventricular function.

Zimring, Howard J.; Fitzgerald, Robert L.; Engler, Robert L.; Ito, Bruce R.

doi:10.1161/01.cir.89.4.1819

Cited by 14 publications

(5 citation statements)

References 29 publications

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“…These new MCE data in humans also extend previous animal studies in several important ways. Our data: a) are consistent with earlier studies in anesthetized dogs 41-43 and pigs 44-46 showing decreased coronary blood flow, and decreased myocardial perfusion by Thallium scintography 47 as well as conventional (i.e., radiolabelled) microspheres 41, 47, 48 ; but b) differ at first glance from more recent studies in conscious dogs and non-human primates in which proximal coronary artery flow increased with cocaine (suggesting that the decreased flow in earlier studies was an artifact of anesthesia). 49 In the later study, however, coronary sinus pH fell despite increased large artery flow, suggesting impaired microvascular perfusion— which we have now shown directly in conscious humans.…”

Section: Discussionsupporting

confidence: 93%

Cocaine-Induced Vasoconstriction in the Human Coronary Microcirculation

et al. 2013

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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.

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Section: Discussionsupporting

confidence: 93%

Cocaine-Induced Vasoconstriction in the Human Coronary Microcirculation

et al. 2013

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“…First, cocaine, due to its adrenergic stimulation, causes an increase in heart rate, blood pressure, and LV contractility [129]. Second, documented in several animal studies [98,[130][131][132][133][134][135] is coronary vasoconstriction associated with cocaine use, due to the stimulation of coronary arterial-adrenergic receptors [136,137]. These studies demonstrated that cocaine administered intravenously caused a decrease in coronary artery caliber and decreased coronary blood flow.…”

Section: Cardiovascular Toxicitymentioning

confidence: 96%

Side Effects of Cocaine Abuse: Multiorgan Toxicity and Pathological Consequences

Riezzo

Fiore²,

Carlo³

et al. 2012

CMC

178

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Cocaine is a powerful stimulant of the sympathetic nervous system by inhibiting catecholamine reuptake, stimulating central sympathetic outflow, and increasing the sensitivity of adrenergic nerve endings to norepinephrine (NE). It is known, from numerous studies, that cocaine causes irreversible structural changes on the brain, heart, lung and other organs such as liver and kidney and there are many mechanisms involved in the genesis of these damages. Some effects are determined by the overstimulation of the adrenergic system. Most of the direct toxic effects are mediated by oxidative stress and by mitochondrial dysfunction produced during the metabolism of noradrenaline or during the metabolism of norcocaina, as in cocaine-induced hepathotoxicity. Cocaine is responsible for the coronary arteries vasoconstriction, atherosclerotic phenomena and thrombus formation. In this way, cocaine favors the myocardial infarction. While the arrhythmogenic effect of cocaine is mediated by the action on potassium channel (blocking), calcium channels (enhances the function) and inhibiting the flow of sodium during depolarization. Moreover chronic cocaine use is associated with myocarditis, ventricular hypertrophy, dilated cardiomyopathy and heart failure. A variety of respiratory problems temporally associated with crack inhalation have been reported. Cocaine may cause changes in the respiratory tract as a result of its pharmacologic effects exerted either locally or systemically, its method of administration (smoking, sniffing, injecting), or its alteration of central nervous system neuroregulation of pulmonary function. Renal failure resulting from cocaine abuse has been also well documented. A lot of studies demonstrated a high incidence of congenital cardiovascular and brain malformations in offspring born to mothers with a history of cocaine abuse.

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“…In this study, plasma cocaine concentrations were similar to the levels achieved in our study. Similarly, Zimring [10], in an anaesthetized pig model, found a decrease of 48% in the segment shortening, independent of changes in the coronary blood flow. The reduction of the left ventricular function was observed even when the coronary perfusion pressure was kept constant.…”

Section: Discussionmentioning

confidence: 81%

“…Cocaine also causes coronary vasoconstriction by two mechanisms, one secondary to the adrenergic stimulation itself, and a second one, independent of cathecolamines, owing to an enhanced calcium transport into the vascular smooth muscle [9]. It has been speculated that in patients with previous coronary artery disease, the coronary vasoconstriction provoked by cocaine superimposed to a fixed coronary stenosis, along with the increased oxygen consumption, could explain the cocaine‐induced myocardial ischaemia and, as a consequence, the left ventricular dysfunction [10,11]. However, both clinical as well as experimental data suggest that, besides the ischaemia, several other mechanisms including a direct depressant effect may also play a role in the cocaine‐induced left ventricular dysfunction [12,13].…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide inhibition intensifies the depressant effect of cocaine on the left ventricular function in anaesthetized pigs

Roig

Melis

Heras

et al. 2000

Eur J Clin Investigation

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Myocardial ischaemia and left ventricular dysfunction have been described in cocaine users. Whether nitric oxide (NO) inhibition may potentiate the effects of cocaine on coronary circulation and ventricular function is still unknown. In order to test this hypothesis, 38 pentobarbital-anaesthetized pigs were instrumented for systolic blood pressure, coronary blood flow, left ventricular dp/dt, cardiac output, left ventricular end-diastolic and end-systolic lengths and shortening fraction. The pigs were randomized into three groups: control group: i.v. saline (n = 5); group 1: i.v. cocaine, 10 mg kg-1 over 20 min (n = 17); group 2: the same doses of cocaine 30 min after i.c. L-NAME 20 microg/kg min-1 infusion (n = 16). In order to know whether the observed effects were specific of NO inhibition, in five pigs i.c. L-arginine was simultaneously infused with L-NAME, in five pigs i.c. NTG, an endothelial-independent vasodilator, was simultaneously infused with L-NAME before cocaine was administered, and in nine additional pigs the proximal left anterior descending (LAD) flow was reduced to around 20% of the basal value by means of a mechanical occluder before cocaine was administered. Cocaine i.v did not change the coronary blood flow, while it induced a significant reduction in cardiac output, left ventricular dp/dt and shortening fraction (15 +/- 4-8 +/- 4%, P < 0.05). When cocaine was administered after L-NAME infused i.c. during 30 min, a significantly more severe reduction of the shortening fraction (12 +/- 3-4 +/- 2%, P < 0.0001) was induced; this effect was abolished by simultaneous perfusion of L-arginine i.c. NTG. The results when cocaine was administered after the 20% LAD flow reduction by mechanical occluder did not differ from those of cocaine alone. NO inhibition intensifies the cocaine-induced left ventricular dysfunction.

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Intracoronary versus intravenous effects of cocaine on coronary flow and ventricular function.

Cited by 14 publications

References 29 publications

Cocaine-Induced Vasoconstriction in the Human Coronary Microcirculation

Cocaine-Induced Vasoconstriction in the Human Coronary Microcirculation

Side Effects of Cocaine Abuse: Multiorgan Toxicity and Pathological Consequences

Nitric oxide inhibition intensifies the depressant effect of cocaine on the left ventricular function in anaesthetized pigs

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