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

Abstract

Background. Prior studies in experimental canine models bave demonstrated that intravenous cocaine administration causes myocardial depression. The purpose of the present study was to establish the mechanisms of cocaine's actions on myocardial and left ventricular performance after single intravenous bolus doses in conscious, chronically instrumented dogs, in which the full autonomic influences of cocaine would be manifest. Methods and Results. In the intact state, cocaine (1 mg/kg) caused a transient decrease in left ventricular dP/dt (baseline; 3,086±107 mm Hg/sec; 2.5 minutes, 2,649±114 mm Hg; p<0.05) followed by a 25±4% increase in left ventricular dP/dt that peaked at 15 minutes (left ventricular dP/dt, 3,751±127 mm Hg/sec, p<0.01) and remained elevated during the 30-minute period of observation. Both the initial depression and the sustained increase in left ventricular contractile response were dose related. The increase in left ventricular dP/dt persisted under circumstances in which the responses were normalized for changes in heart rate and preload that accompanied cocaine administration. The positive inotropic effects were abolished by full autonomic or selective β-adrenergic blockades. Finally, both cardiac output (baseline, 2,461±142 min/mL; peak [5 minutes], 3,434±218 mL/min; p<0.051 and left ventricular stroke work (baseline, 39±5 g · m; peak, 49±6 g · m; p<0.05) were increased at all times after cocaine administration, suggesting that pump performance was enhanced, despite early reductions in myocardial contractility. Similarly, indexes of early diastolic filling were enhanced despite transient early prolongation in isovolumic relaxation. Conclusions. Acute intravenous cocaine administration (0.1-2 mg/kg) has a biphasic effect on myocardial and left ventricular function with a transient depression followed by significant sustained increases in left ventricular contractility. The results are in keeping with an early local effect followed by significant adrenergic stimulation, which may be obscured by anesthesia or masked by changes in loading conditions.