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 excitability and prolonged ventricular conduction time in hearts from rabbits treated with a lard diet compared to those from rabbits treated with 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 isolated sarcolemma was significantly higher in the safflower oil group (31.1 +/- 5.6%) than in the lard group (18.8 +/- 3.9%, P < .001). During quinidine (3 microM) perfusion, the threshold current was significantly greater in the lard group (0.44 +/- 0.18 mA) compared to the safflower oil group (0.24 +/- 0.11 mA, P < .05). During procainamide and tocainide perfusion, the threshold current was similar in the lard and safflower oil groups. During quinidine perfusion, greater prolongation of the endocardial monophasic action potential duration was observed in the safflower oil group (217 +/- 15 msec) compared to the lard group (196 +/- 24 msec, P < .05). Procainamide and tocainide effects on monophasic action potential duration were similar in the lard and safflower oil groups. Thus, dietary fat modulates the effects of the lipophilic drug quinidine on ventricular excitability and repolarization.
Department of Medicine, University of Calgary, Alberta, Canada.
A M
AM
Gillis
M
M
Choi
H J
HJ
Mathison
H G
HG
Parsons
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D011342:Procainamide / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*; D011817:Rabbits; D012508:Sarcolemma / Q000737:chemistry; D016677:Tocainide / Q000494:pharmacology*
D004041:Dietary Fats; D005227:Fatty Acids; D016677:Tocainide; D011802:Quinidine; D011342:Procainamide