Effects of cocaine and alcohol alone and in combination on cardiovascular performance in dogs

With the proliferation of cocaine abuse, increased incidence of catastrophic cardiovascular events such as angina pectoris, myocardial infarction, ventricular arrhythmias, or sudden death are reported. Many of these patients also drink alcohol before and after cocaine use, leading to a high frequency of simultaneous exposure to both the drugs. Cocaine and ethanol's independent effects on cardiodynamics are well documented, but their combined effects on complete cardiovascular hemodynamics remain unknown. Are effects additive, synergistic, or antagonistic?

Sixteen dogs were instrumented to pass cardiac catheters into right and left ventricles. After they recovered from the effects of anesthesia, experiments were performed. In phase I, 18 experiments (6 dogs) established the dose by dose response curve. In phase II and III, another 10 dogs, subjected to 30 experiments, were given i.v. cocaine followed by ethanol and vice versa to study their effects on hemodynamics and coronary flow reserve.

Phase I: doses of cocaine (2 mg/kg) and ethanol (400 mg/kg) were established. Phase II: cocaine increased heart rate, blood pressure and dP/dt but ethanol administered after cocaine attenuated these effects [first derivative of the left ventricular pressure (dP/dt) < 2052 +/- 104 from 2614 +/- 110 mm Hg/sec; P < 0.04)]. Phase III: alcohol mildly increased hemodynamic parameters. Cocaine's administration as the second drug had synergistic excitatory effects (dP/dt > 3300 +/- 160 from 2854 +/- 142 mm Hg/sec; P < 0.004).

Cocaine increased heart rate, blood pressure, and dP/dt but reduced CFR. Alcohol mildly increased the hemodynamic variables and CFR. Combined cocaine and alcohol attenuated the excitatory effects of cocaine significantly. A reversed drug combination (ie, alcohol then cocaine) generated synergistic excitatory effects on the cardiovascular system of the dogs.