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 1 (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 < NS). Phase III: Caffeine mildly increased hemodynamic parameters but reduced dP/dt. Cocaine's administration as the second drug had synergistic excitatory effects (dP/dt increased to 6166 ± 160 from 5055 ± 142 mm Hg/s; p < 0.04). CFR decreased significantly. Conclusion: Cocaine increased heart rate, blood pressure and dP/dt but reduced CFR. Caffeine mildly increased the hemodynamic variables but decreased CFR. Combined cocaine + caffeine attenuated the excitatory effects of cocaine significantly. A reversed drug combination i.e., caffeine + cocaine generated synergistic excitatory effects on the cardiovascular system of the dogs. CFR showed significant decrease.