Kinoshita I, Itoh K, Nishida-Nakai M, Hirota H, Otsuji S, Shibata N
Department of Cardiology, Center for Adult Diseases, Osaka, Japan.
Jpn Circ J. 1994 Dec;58(12):903-12. doi: 10.1253/jcj.58.903.
The effects of dietary supplementation with eicosapentaenoic acid (EPA) on ventricular arrhythmias during myocardial infarction were examined in a canine model. EPA was incorporated into cellular membranes after ingestion of EPA-ester (100 mg/kg body weight/day) for 8 weeks. The ratio of EPA to arachidonic acid (AA) in platelet cell membranes and myocardial microsomes was significantly increased (7% to 37% in platelet cell membranes; p < 0.01, 3% to 12% in non-infarcted cardiac microsomes; p < 0.01, and from 2% to 8% in infarcted cardiac microsomes; p < 0.01). Dietary supplementation with EPA significantly reduced the incidence and severity of arrhythmias during coronary artery occlusion. Immediately after coronary artery occlusion, all of the animals in the control group that were given a toxic dose of digitalis developed ventricular tachycardia (VT) or ventricular fibrillation (Vf), whereas none of the animals in the EPA-supplement group developed VT or Vf within 15 min after administration of digitalis. Regardless of the presence of an infarcted area, the specific activity of the Ca(2+)-pump enzyme ((Ca(2+)-Mg2+)-ATPase) within the myocardial microsomal fraction of the EPA-supplemented group was significantly higher than in that of the control group (Vmax: 140.5 +/- 19.1 vs 94.8 +/- 28.9 nmol/mg/min in non-infarcted cardiac microsomes, p < 0.01, 130.9 +/- 18.4 vs 90.2 +/- 26.4 nmol/mg/min in infarcted cardiac microsomes, p < 0.01, EPA vs control group, respectively). The specific activities of the Na(+)-pump enzyme ((Na(+)-K+)-ATPase) and NADPH-dependent cytochrome C reductase in infarcted and non-infarcted cardiac microsomes did not differ between these groups. These results indicate that EPA supplementation increases the (Ca(2+)-Mg2+)-ATPase activity within myocardial membranes that is involved in Ca2+ metabolism in myocardial cells by increasing the ratio of EPA to AA within cellular membranes. These cellular alterations are likely to reduce the severity of ventricular arrhythmias by inhibiting the rapid accumulation of intracellular Ca2+ following ischemia.
在犬类模型中研究了膳食补充二十碳五烯酸（EPA）对心肌梗死期间室性心律失常的影响。在摄入EPA酯（100mg/kg体重/天）8周后，EPA被整合到细胞膜中。血小板细胞膜和心肌微粒体中EPA与花生四烯酸（AA）的比例显著增加（血小板细胞膜中从7%增至37%；p<0.01，非梗死心肌微粒体中从3%增至12%；p<0.01，梗死心肌微粒体中从2%增至8%；p<0.01）。膳食补充EPA显著降低了冠状动脉闭塞期间心律失常的发生率和严重程度。冠状动脉闭塞后立即给予洋地黄中毒剂量，对照组所有动物均出现室性心动过速（VT）或室颤（Vf），而EPA补充组动物在给予洋地黄后15分钟内均未出现VT或Vf。无论是否存在梗死区域，EPA补充组心肌微粒体部分中Ca(2+)-泵酶（(Ca(2+)-Mg2+)-ATPase）的比活性均显著高于对照组（非梗死心肌微粒体中Vmax：140.5±19.1对94.8±28.9nmol/mg/min，p<0.01，梗死心肌微粒体中130.9±18.4对90.2±26.4nmol/mg/min，p<0.01，分别为EPA组与对照组）。梗死和非梗死心肌微粒体中Na(+)-泵酶（(Na(+)-K+)-ATPase）和NADPH依赖性细胞色素C还原酶的比活性在这些组之间没有差异。这些结果表明，补充EPA通过增加细胞膜内EPA与AA的比例，增加了心肌膜内参与心肌细胞Ca2+代谢的(Ca(2+)-Mg2+)-ATPase活性。这些细胞改变可能通过抑制缺血后细胞内Ca2+的快速积累来降低室性心律失常的严重程度。
