Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Sep 1994
Systemic and coronary hemodynamic effects of repetitive cocaine administration in conscious dogs.
The cardiovascular actions of cocaine are complex, and previous studies suggest that tachyphylaxis to the positive chronotropic and pressor effects of cocaine may develop after repetitive administration. We examined changes in systemic and coronary hemodynamics when single or multiple doses of intravenous (i.v.) cocaine were administered to conscious dogs. Dogs were chronically instrumented for measurement of aortic blood pressure (BP) and left ventricular pressure (LVP), LV dP/dtmax and dP/dt50, subendocardial segment length (%SS), diastolic coronary blood flow (CBF) velocity, and cardiac output (CO). ⋯ Cocaine also caused significant increases in baseline HR, MAP, LVSP, and PWI between doses given on the same day at 1-h intervals, but the absolute value of the peak response to cocaine of these hemodynamic parameters was independent of dosing regimen. These results were confirmed when we administered four doses of 0.8 mg/kg cocaine at 1-h intervals. The results indicate that baseline changes in systemic hemodynamic variables are a predominant feature of repetitive administration of lower doses of cocaine (< or = 0.8 mg/kg), but administration of higher doses of cocaine (> or = 8 mg/kg) at 1-h intervals caused tachyphylaxis to the hypertensive actions and myocardial oxygen consumption effects of cocaine.