INFLUENCE OF DIETARY-FAT ON THE PHARMACODYNAMICS OF QUINIDINE, PROCAINAMIDE AND TOCAINIDE IN ISOLATED-PERFUSED RABBIT HEARTS

We have reported previously that propafenone decreased ventricular exc itability and prolonged ventricular conduction time in hearts from rab bits treated with a lard diet compared to those from rabbits treated w ith a safflower oil diet. We hypothesized that these effects might be modulated by the lipid solubility of the drug. Accordingly, we studied the effects of dietary fat on the pharmacodynamics of the hydrophilic drugs, procainamide and tocainide, and the lipophilic drug, quinidine . Weanling rabbits were fed diets of 10% w/w lard or safflower oil for 40 days. Differences in electrophysiological variables were compared at base line and during drug perfusion. The linoleic acid content of i solated sarcolemma was significantly higher in the safflower oil group (31.1 +/- 5.6%) than in the lard group (18.8 +/- 3.9%, P < .001). Dur ing quinidine (3 mu M) perfusion, the threshold current was significan tly greater in the lard group (0.44 +/- 0.18 mA) compared to the saffl ower oil group (0.24 +/- 0.11 mA, P < .05). During procainamide and to cainide perfusion, the threshold current was similar in the lard and s afflower oil groups. During quinidine perfusion, greater prolongation of the endocardial monophasic action potential duration was observed i n the safflower oil group (217 +/- 15 msec) compared to the lard group (196 +/- 24 msec, P < .05). Procainamide and tocainide effects on mon ophasic action potential duration were similar in the lard and safflow er oil groups. Thus, dietary fat modulates the effects of the lipophil ic drug quinidine on ventricular excitability and repolarization.