Prevention of fatal cardiac arrhythmias by polyunsaturated fatty acids
Prevention of fatal cardiac arrhythmias by polyunsaturated fatty acids
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DOI：
10.1093/ajcn/71.1.202s
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发表时间：
2000-01-01
影响因子：
7.1
通讯作者：
Leaf, A
中科院分区：
文献类型：
--
作者：
Kang, JX;Leaf, A
在动物饲养研究中，可能在人类中，n-3多不饱和脂肪酸（PUFA）可预防致命性缺血诱导的心律失常。我们发现，n-3 PUFA也可以预防手术准备，清醒，运动犬的心律失常。用培养的新生大鼠心肌细胞自发性收缩模型研究了n-3 PUFAs的抗心律失常作用机制。向心肌细胞灌注液中加入致心律失常毒素（如哇巴因、高钙、溶血磷脂酰胆碱、β-肾上腺素能激动剂、酰基肉毒碱和钙离子载体）可引起培养的心肌细胞心动过速、挛缩和纤颤。在添加毒素之前向灌流液中添加二十碳五烯酸（EPA：5-15 μ mol/L）可以预防预期的快速心律失常。如果心律失常是第一次诱发的，在灌流液中加入EPA可以终止心律失常。这种抗肿瘤作用发生与饮食n-3和n-6 PUFA;饱和脂肪酸和单不饱和油酸诱导没有这样的行动。花生四烯酸（AA; 20：4 n-6）是异常的，因为在三分之一的测试中，它引起了严重的心律失常，这是由AA的环氧合酶代谢产物引起的。当环氧合酶抑制剂与AA一起加入时，抗肿瘤作用与EPA和DHA相似。n-3和n-6 PUFA的作用是通过将引发动作电位所需的电刺激增加约50%并将相对不应期延长约150%来电稳定心脏中的每个肌细胞。这些电生理效应是由于游离PUFA调节肌细胞中钠电流和钙电流的作用所致。PUFA还调节钠和钙通道，并在脑细胞中具有抗惊厥活性。
In animal feeding studies, and probably in humans, n-3 polyunsaturated fatty acids (PUFAs) prevent fatal ischemia-induced cardiac arrhythmias. We showed that n-3 PUFAs also prevented such arrhythmias in surgically prepared, conscious, exercising dogs. The mechanism of the antiarrhythmic action of n-3 PUFAs has been studied in spontaneously contracting cultured cardiac myocytes of neonatal rats. Adding arrhythmogenic toxins (eg, ouabain, high Ca2+, lysophosphatidylcholine, beta-adrenergic agonist, acylcarnitine, and the Ca2+ ionophore) to the myocyte perfusate caused tachycardia, contracture, and fibrillation of the cultured myocytes. Adding eicosapentaenoic acid (EPA: 5-15 mu mol/L) to the superfusate before adding the toxins prevented the expected tachyarrhythmias. If the arrhythmias were first induced, adding the EPA to the superfusate terminated the arrhythmias. This antiarrhythmic action occurred with dietary n-3 and n-6 PUFAs; saturated fatty acids and the monounsaturated oleic acid induced no such action. Arachidonic acid (AA; 20:4n-6) is anomalous because in one-third of the tests it provoked severe arrhythmias, which were found to result from cyclooxygenase metabolites of AA. When cyclooxygenase inhibitors were added with the AA, the antiarrhythmic effect was like those of EPA and DHA. The action of the n-3 and n-6 PUFAs is to stabilize electrically every myocyte in the heart by increasing the electrical stimulus required to elicit an action potential by approximate to 50% and prolonging the relative refractory time by approximate to 150%. These electrophysiologic effects result from an action of the free PUFAs to modulate sodium and calcium currents in the myocytes. The PUFAs also modulate sodium and calcium channels and have anticonvulsant activity in brain cells.