Acute intravenous cocaine causes transient depression followed by enhanced left ventricular function in conscious dogs.

Stambler, Bruce S.; Komamura, Kazuo; Ihara, Tadashi; Shannon, Richard P.

doi:10.1161/01.cir.87.5.1687

Cited by 27 publications

(15 citation statements)

References 43 publications

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“…Under circumstances in which anesthetized animal models have been studied, acute cocaine administration has been shown to be a myocardial depressant (Bedotto et al, 1988;Hale et al, 1989Hale et al, , 1991Fraker et al, 1990;Hayes et al, 1991). In contrast, several laboratories, including our own, have demonstrated that in conscious, chronically instrumented dogs, cocaine has a sympatho-stimulatory effect in increasing myocardial contractility and heart rate (Wilkerson, 1988;Kiritsy-Roy et al, 1990, Knuepfer andBranch, 1992;Shannon et al, 1993Shannon et al, , 1995Shannon et al, , 1996Shannon et al, , 2000Stambler et al, 1993). The critical dependence of cocaine on the integrity of sympathetic nervous system likely reconciles these differences.…”

Section: Discussionmentioning

confidence: 94%

“…Importantly, there is no sensitization that occurs following chronic cocaine binging and no effect on resting hemodynamics. We did not attempted to overcome hemodynamic tolerance by increasing the dose, as 1 mg/kg is the near maximal dose of cocaine tolerated by a conscious dog without agitation and seizures Stambler et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Drug was administered via the right atrial catheter. The individual dose was chosen as the maximally tolerated dose in a conscious dog that did not result in uncontrollable agitation based on our prior studies (Shannon et al, , 1995Stambler et al, 1993). This protocol was repeated for total of 8 days (4 days a week for 2 weeks in continuation).…”

Section: Methodsmentioning

confidence: 99%

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Chronic Exposure to Cocaine Binging Predisposes to an Accelerated Course of Dilated Cardiomyopathy in Conscious Dogs following Rapid Ventricular Pacing

Parikh

Nikolaidis²,

Stolarski³

et al. 2005

J Pharmacol Exp Ther

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Despite extensive study, the extent to which cocaine use predisposes to cardiac injury remains unknown. We hypothesized that chronic cocaine binging would increase susceptibility to a subsequent cardiac insult, even in the absence of demonstrable effects on baseline hemodynamics. We studied progression of dilated cardiomyopathy (DCM) induced by rapid ventricular pacing (240 beats per minute) in five conscious, chronically instrumented dogs, after exposure to repetitive cocaine binging (COC) in the form of four consecutive 1 mg/kg i.v. boluses daily for 8 days, to simulate human cocaine abuse. We compared the results with nine control dogs (CON) undergoing the exact pacing protocol, without prior cocaine exposure. Baseline hemodynamics were not significantly altered by chronic cocaine exposure. Following 2 weeks of pacing, COC dogs exhibited accelerated progression to DCM, depressed plasma nitric oxide levels (CON, 17 Ϯ 2 M; COC, 10 Ϯ 2 M, p Ͻ 0.05), and a significantly greater increase in plasma epinephrine (CON, 33 Ϯ 6 pg/ml; COC, 104 Ϯ 24 pg/ml). After only 2 weeks of pacing, COC dogs demonstrated progressive DCM of a magnitude comparable with end-stage pacing-induced DCM. Chronic cocaine binging increases susceptibility to a subsequent myocardial insult and accelerates progression of DCM in conscious dogs following rapid pacing. These data suggest that although chronic cocaine use alone may not affect myocardial function, it predisposes to greater susceptibility to a superimposed insult.Cocaine is responsible for the greatest number of hospitalizations in United States attributable to illicit drug use. According to a survey, it was reported that more than 25 million people had used cocaine at some time in their life, and 1.5 million were chronic users. The effects of cocaine on the cardiovascular system are multifaceted and remain incompletely understood. Cardiovascular manifestations of cocaine abuse include chest pain, myocardial ischemia and infarction, arrhythmias, infective endocarditis, aortic dissection and development of dilated cardiomyopathy, and heart failure (Wiener et al., 1986;Kloner et al., 1992;Mouhaffel et al., 1995). There have been increasing numbers of reports of dilated cardiomyopathy in cocaine abusers. Wiener et al. (1986) were the first to describe the occurrence of DCM in the absence of atherosclerotic coronary artery disease in two patients who were cocaine abusers.Chronic cocaine use in young men who were normotensive and had no symptoms or signs of heart diseases had electrocardiographic and echocardiographic abnormalities including LV hypertrophy (54%), LVEF Ͻ0.45 (4%), increased QRS voltage (23%), and episodes of ST-segment elevation on ambulatory monitoring (33%) (Chakko and Myerburg, 1995). However, the mechanism whereby chronic cocaine use predisposes to myocardial injury remains incompletely understood.There has been both confusion and controversy as to whether cocaine use predisposes to decreased myocardial contractility. Much of the evidence of cocaine-induced myoca...

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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Chronic Exposure to Cocaine Binging Predisposes to an Accelerated Course of Dilated Cardiomyopathy in Conscious Dogs following Rapid Ventricular Pacing

Parikh

Nikolaidis²,

Stolarski³

et al. 2005

J Pharmacol Exp Ther

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“…The mechanisms attributable to cocaine include stimulation of the neuronal release of catecholamines from both the central vasomotor center and the adrenal medulla. [5][6][7][8][9][10] Second, cocaine is known to be a potent inhibitor of norepinephrine reuptake, which constitutes the major mechanism for modulating the activity of the agonist at the postsynaptic receptor. [11][12][13] Third, cocaine has been shown to have direct effects to impair baroreflex functions independently of autonomic effects.…”

mentioning

confidence: 99%

“…In particular, anesthesia has been shown to dramatically alter the hemodynamic profile of intravenous cocaine by mitigating its central nervous system effects and highlighting its local anesthetic properties. 6,17 Similarly, it has been shown that the state of resting sympathetic nervous system activation is a dominant determinant of the ultimate cardiovascular profile of intravenous cocaine administration in rats. 9,18 -20 Accordingly, the purpose of the present study was to determine whether or to what extent cardiac nerves are important in mediating cardiovascular consequences of cocaine.…”

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confidence: 99%

Role of Cardiac Nerves in the Cardiovascular Response to Cocaine in Conscious Dogs

2001

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Background-Although the cardiovascular toxicity of cocaine is well recognized, considerable controversy remains as to the relative contribution of local norepinephrine reuptake inhibition versus central stimulatory effects of cocaine in eliciting its cardiovascular actions. The purpose of the present study was to determine the role of cardiac nerves in mediating the left ventricular (LV) and coronary hemodynamic responses to cocaine. Methods and Results-We studied the cardiovascular response to acute cocaine administration (1 mg/kg) in 10 intact, conscious dogs and 6 dogs with ventricular denervation (VD). There were no significant differences in baseline hemodynamic parameters or plasma catecholamines between the 2 groups. In response to acute cocaine, LV and coronary hemodynamic responses were enhanced in the VD dogs. The enhanced systemic pressor and heart rate responses in VD dogs suggest that cardiac nerves mitigate the response to cocaine through ventricular mechanoreceptors rather than mediating the responses. Conclusions-These data suggest that peripheral blockade of norepinephrine reuptake is not the principal mechanism of the acute cardiac effects of cocaine. Rather, cardiac nerves modulate the effects of cocaine through baroreflex mechanisms. Thus, individual differences in baroreflex sensitivity may explain the hemodynamic variability observed in response to cocaine. (Circulation. 2001;103:1674-1680.)

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Sympathetic nervous system mediated cardiovascular effects of cocaine are primarily due to a peripheral site of action of the drug

Gillis

Hernandez

Erzouki

et al. 1995

Drug and Alcohol Dependence

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Acute intravenous cocaine causes transient depression followed by enhanced left ventricular function in conscious dogs.

Cited by 27 publications

References 43 publications

Chronic Exposure to Cocaine Binging Predisposes to an Accelerated Course of Dilated Cardiomyopathy in Conscious Dogs following Rapid Ventricular Pacing

Chronic Exposure to Cocaine Binging Predisposes to an Accelerated Course of Dilated Cardiomyopathy in Conscious Dogs following Rapid Ventricular Pacing

Role of Cardiac Nerves in the Cardiovascular Response to Cocaine in Conscious Dogs

Sympathetic nervous system mediated cardiovascular effects of cocaine are primarily due to a peripheral site of action of the drug

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