Effects of cocaine and caffeine alone and in combination on cardiovascular performance: an experimental hemodynamic and coronary flow reserve study in a canine model.

BACKGROUND: With the proliferation of cocaine abuse, increased incidence of catastrophic cardiovascular events like angina pectoris, myocardial infarction, ventricular arrhythmias or sudden death are reported. Cocaine-dependent subjects commonly abuse multiple substances. Many of them drink coffee before and after cocaine use. The high frequency of simultaneous exposure to both the drugs may influence outcome of the cocaine's treatment. Cocaine and caffeine's independent effects on cardiodynamics are documented but to our knowledge combined effects of both on complete cardiovascular hemodynamics remains to be examined. METHODS: Eighteen dogs were instrumented to pass cardiac catheters into right and left heart. The experiments were performed after they recovered from the effects of anesthesia. In phase I (30 experiments on 8 dogs), the doses were established by dose-response curve. In phases II and III, another 10 dogs were subjected to 28 experiments. They were given i.v. cocaine followed by caffeine and vice versa to study their effects on hemodynamics and coronary flow reserve. RESULTS: Phase 1: The doses of cocaine (2 mg/kg) and caffeine (5 mg/kg) were established. Phase II: Cocaine increased heart rate, blood pressure and dP/dt but CFR decreased significantly. Caffeine administered after cocaine attenuated these effects (dP/dt decreased to 4910+/-104 from 5066+/-110 mm Hg s; p

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

BACKGROUND: 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? METHODS: 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. RESULTS: 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). CONCLUSION: 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.