Gillis A M, Choi M, Mathison H J, Parsons H G
Department of Medicine, University of Calgary, Alberta, Canada.
J Pharmacol Exp Ther. 1994 Oct;271(1):176-83.
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.
我们之前曾报道，与食用红花油饮食的家兔心脏相比，普罗帕酮可降低食用猪油饮食的家兔心脏的心室兴奋性，并延长心室传导时间。我们推测这些效应可能受药物脂溶性的调节。因此，我们研究了膳食脂肪对亲水性药物普鲁卡因胺和妥卡尼，以及亲脂性药物奎尼丁药效学的影响。将断乳家兔分别喂食含10%（重量/重量）猪油或红花油的饮食40天。比较基线期和药物灌注期间电生理变量的差异。红花油组分离的肌膜中亚油酸含量（31.1±5.6%）显著高于猪油组（18.8±3.9%，P<.001）。在奎尼丁（3μM）灌注期间，猪油组的阈电流（0.44±0.18 mA）显著高于红花油组（0.24±0.11 mA，P<.05）。在普鲁卡因胺和妥卡尼灌注期间，猪油组和红花油组的阈电流相似。在奎尼丁灌注期间，与猪油组（196±24毫秒）相比，红花油组的心内膜单相动作电位时程延长更明显（217±15毫秒，P<.05）。普鲁卡因胺和妥卡尼对单相动作电位时程的影响在猪油组和红花油组相似。因此，膳食脂肪可调节亲脂性药物奎尼丁对心室兴奋性和复极化的影响。
