Cocaine‐induced microvascular vasoconstriction but differential systemic haemodynamic responses in Yucatan versus Yorkshire varieties of swine

Lin, Miao; Núñez, Boris D.; Susulic, Vojken; Wheeler, Suzanne M.; Carrozza, Joseph P.; Ross, James N.; Morgan, James P.

doi:10.1111/j.1476-5381.1996.tb15227.x

Cited by 10 publications

(6 citation statements)

References 37 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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“…It has been suggested that the coronary artery is more sensitive to endogenous vasoactive substances after chronic cocaine abuse (Jones and Tackett, 1990). Cocaine abuse has been reported to cause an increase in coronary artery vasoconstriction (Vongpatanasin et al, 1997) and recurrent coronary vasoconstriction (Brogan et al, 1992), a decrease in coronary blood flow (Miao et al, 1996), and an increase in myocardial ischemia and infarction (Pitts et al, 1997). Although acute cocaine use is typically considered as a risk factor for acute cardiac events, chronic use may contribute to the development or rapid progression of coronary artery diseases (Wilson, 1998;He et al, 2000).…”

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confidence: 99%

Effects of Cocaine on Nitric Oxide Production in Bovine Coronary Artery Endothelial Cells

He¹,

Yang²,

Zhang³

2005

J Pharmacol Exp Ther

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Cocaine decreases coronary artery endothelial-dependent vasorelaxation. To explore the potential mechanisms, the present study examined the effect of cocaine on nitric oxide release in bovine coronary artery endothelial cells (BCAECs). In the absence of cocaine, basal nitric oxide release from BCAECs continued to accumulate in the medium over the period from 6 to 72 h. Cocaine significantly decreased nitric oxide release at each time point of the study. At 48-h treatment, cocaine (3-30 muM) produced a concentration-dependent decrease in nitric oxide release in BCAECs. In accordance with its inhibition of nitric oxide release, cocaine decreased endothelial nitric-oxide synthase (eNOS) protein levels in BCAECs in a concentration-dependent manner. In addition to the prolonged effect, cocaine pretreatment for 1 h significantly decreased basal and ATP-induced nitric oxide release in BCAECs. Whereas acute cocaine treatment did not affect basal levels of free intracellular calcium concentrations in BCAECs, it significantly decreased the ATP-induced elevation of intracellular calcium and increased its time lag to reach the peak. A quantitative approach by immunofluorescence microscopy revealed that cocaine significantly increased eNOS localized at the cell membrane in BCAECs. Collectively, the results suggest that cocaine inhibits nitric oxide release in BCAECs by decreasing intracellular calcium mobilization, increasing the inactive state of eNOS, and decreasing eNOS protein levels.

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“…The inhibitory effect of cocaine on ventricular function may result from sympathetically mediated vasoconstriction or from its direct negative chronotropic and inotropic actions. Although, cocaine can cause coronary spasm and reduce coronary blood flow (8,9), studies (20,(31)(32)(33)(34) reported that +dP/dt fell after cocaine administration whereas coronary blood flow was either unchanged or actually increased. Doses of 0-50 mg/kg cocaine were found to reduce left ventricular function without inducing coronary spasm and increasing systemic vascular resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have reported a significant influence of cocaine administration on cardiovascular function in pigs, dogs, ferrets and rats (5)(6)(7). Nunez and Morgan (8,9) reported that acute or chronic cocaine exposure induced microvascular vasoconstriction and produced myocardial ischemia and infarction. Stambler et al (10) reported that, in conscious dogs, cocaine showed a biphasic effect on blood pressure, first causing transient depression followed by enhanced left ventricular function.…”

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confidence: 99%

Differential Depressant Effects of General Anesthetics on the Cardiovascular Response to Cocaine in Mice

Wang¹,

Hampton²,

DeAngelis³

et al. 1999

Experimental Biology and Medicine

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In recent years, murine models have gained increasing importance for studies of cardiovascular physiology and pharmacology, largely due to the development of transgenic strains with specific alterations in phenotype. Differential effects of general anesthetic agents on the cardiovascular responses to cocaine have been reported in larger mammals; therefore, we studied the effects of commonly used anesthetics on heart function and on blood pressure responses to cocaine in Swiss Webster mice. We positioned a polyethylene catheter (PE-10) in the right carotid artery or left ventricle of mice anesthetized with equivalent anesthetic dose of either ketamine-xylazine (KX, 40 mg/kg + 5 mg/kg), pentobarbital (PEN, 40 mg/kg) or a-chloralose-urethane (CU, 80 mg/kg + 100 mg/kg). Cocaine (0.3 mg/kg, 1 mg/kg and 3 mg/kg) was administrated via the left jugular vein by bolus injection. In the KX group, the basal mean arterial pressure (MAP) and systolic left ventricular pressure (LVP) were 110 12 and 120 f 13 mmHg, respectively, close to conscious values. However, PEN and CU significantly decreased the basal parameters (P < 0.01 compared to the KX group). The lowest dose of cocaine (0.3 mg/kg) elicited minimal changes. Significant responses were obtained with a 1-mg/kg dose of cocaine ( P < 0.01 compared to baseline). However, at 3 mg/kg, a toxic effect of cocaine appeared in all three anesthetic groups. Compared to published conscious animal data, anesthetic agents attenuated the cardiovascular effects of cocaine. Taken together, our results indicate that minimally effective doses of general anesthetics may significantly alter the basal hemodynamic state and the responses to sympathomimetic agents in the murine model, as has been reported in larger mammalian species. We concluded that anesthesia with ketamine-xylazine provides baseline hemodynamic values close to reported values in conscious animals, but also attenuates the hemodynamic response to cocaine. [P.S.E.B.M. 1999[P.S.E.B.M. , Vol 2211 n recent years, there has been a dramatic increase in the number of patients with a history of cocaine abuse who I demonstrate various cardiovascular signs and symptoms, such as acute myocardial ischemia and infarction, arrhythmia and sudden death, contraction band necrosis, myocarditis, cardiomyopathy, and hypertension (1-3). Moreover, long-term exposure to cocaine has been shown to induce uterine and fetal blood flow disorders, fetal growth restriction, and hypoxia (4). Studies have reported a significant influence of cocaine administration on cardiovascular function in pigs, dogs, ferrets and rats (5-7). Nunez and Morgan (8, 9) reported that acute or chronic cocaine exposure induced microvascular vasoconstriction and produced myocardial ischemia and infarction. Stambler et al. (10) reported that, in conscious dogs, cocaine showed a biphasic effect on blood pressure, first causing transient depression followed by enhanced left ventricular function. The changes in cardiovascular function caused by cocaine were associated with catecho...

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Cocaine‐induced microvascular vasoconstriction but differential systemic haemodynamic responses in Yucatan versus Yorkshire varieties of swine

Cited by 10 publications

References 37 publications

Cocaine-Induced Vasoconstriction in the Human Coronary Microcirculation

Cocaine-Induced Vasoconstriction in the Human Coronary Microcirculation

Effects of Cocaine on Nitric Oxide Production in Bovine Coronary Artery Endothelial Cells

Differential Depressant Effects of General Anesthetics on the Cardiovascular Response to Cocaine in Mice

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