Pharmacodynamics of Propafenone in Isolated, Perfused Rabbit Hearts

Background. The fatty acid composition of the phospholipids in sarcolemma may significantly influence cell membrane functions. We evaluated the effects of dietary fat on the pharmacodynamics of the antiarrhythmic drug propafenone in isolated, perfused rabbit hearts. Methods and Results. Three groups of weanling rabbits (n=9 each group) were fed diets of 10%O wtlwt lard, fish oil, or safflower oil for 40 days. Differences in electrophysiological variables were assessed at baseline and during propafenone perfusion. Myocardial concentration-effect relations were determined by plotting electrophysiological effects versus coronary sinus propafenone concentrations. The linoleic acid content of isolated sarcolemma was higher in the safflower group (33.4±11.4%o) than in the lard (13.4±2.3%, p<0.01) and fish oil (8.5±1.4%, p<0.01) groups, whereas the o-3 fatty acid content was higher in the fish oil group (p<0.01). During propafenone perfusion, greater changes in ventricular conduction time were observed in the lard group (22± 11 msec) than in the safflower oil group (10±7 msec, p<0.05), whereas changes in ventricular conduction time in the fish oil group (16±7 msec) were intermediate between the lard and safflower oil groups. The slopes of the linear myocardial concentrationeffect relations describing changes in QRS duration were steeper in the lard group (0.22±0.07 msec/lug/ml) than in the safflower oil group (0.13±0.04 msecl,ug/ml,p<0.01) but not in the fish oil group (0.17±0.08 msec/,ug/ml, p=NS). Strength-interval curves were similar at baseline in all three groups. During propafenone perfusion, the threshold current was increased significantly at long coupling intervals (250-380 msec) in the lard group (1.8±1.0 mA) compared with the safflower oil group (0.8±0.6 mA, p<0.05) but not compared with the fish oil group (1.2±0.6 mA, p=NS). Conclusions. Dietary fat significantly alters the fatty acid composition of the phospholipids in sarcolemma. Propafenone effects on ventricular conduction time and ventricular excitability are significantly influenced by the type of dietary fat. (Circukltion 1992;85:1501-1509)