COMBINED EFFECTS OF CAFFEINE AND NICOTINE ON CARDIOVASCULAR HEMODYNAMICS IN CANINE MODEL

The independent effects of caffeine and nicotine on cardiodynamics are well documented, but combined effects of both are not reported. Initi ally, in phase I, 18 experiments were performed to study the dose-resp onse curve of both the drugs. In phases II and III, 13 mongrel dogs we re subjected to 30 experiments. In phase II, caffeine, 5 mg/kg, was gi ven i.v. followed by nicotine, 50 mu g/kg, and in phase III, the seque nce of drug administration was reversed to study the effects on hemody namics. In phase II, caffeine did net show significant changes in all the cardiovascular parameters, but nicotine administration after caffe ine produced marked significant synergistic excitatory effects: the ra te of increase of the first derivative of left ventricular pressure (d P/dt) increased from 1,101 +/- 111 to 3,194 +/- 872 (p < 0.003). In ph ase III, nicotine significantly increased heart rate, mean arterial pr essures: left ventricular end-diastolic pressure (LVEDP); and pulmonar y artery, pulmonary capillary wedge, and right atrial pressures. Nicot ine increased dP/dt (964 +/- 182 to 1,639 +/- 60 mm Hg/s; p < 0.004). The excitatory effects of nicotine were attentuated by administration of caffeine (dP/dt, 918 +/- 140 reduced to 715 +/- 144 mm Hg/s; p < 0. 04). Caffeine and nicotine, alone, caused nonsignificant and significa nt increases in hemodynamics, respectively. In combination, caffeine nicotine administration produced significant synergistic excitatory e ffects in dogs. On the other hand, the nicotine + caffeine combination caused attentuation by caffeine of the excitatory effects produced by nicotine.