Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids.

Abstract

A specially prepared dog model of myocardial infarction was used to test the efficacy of the long-chain polyunsaturated fish oil 3 fatty acids eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n-3) acids to prevent ischemiainduced malignant cardiac arrhythmias. The dogs had sustained a prior experimental myocardial infarction from ligation of the left anterior descending coronary artery, and a hydraulic cuff was implanted around the left circumflex artery at that operation. After recovery from that procedure the animals were tested during a treadmill exercise test. With compression of the left circumflex artery sensitive animal will predictably develop ventricular fibrillation (VF). In such prepared dogs an emulsion of fish oil fatty acids was infused i.v. over a 50-to 60-min period just before the exercise-plus-ischem test, and the effect on development ofVF was recorded. The infusion was 100 ml of a 10% (vol/vol) emulsion of a fish oil concentrate containing 70% W3 fatty acids with free eicosapentaenoic acid and docosahexaenoic acid composing 33.9% and 25.0% of that total, respectively. Alternatively, some animals similarly received an emulsion containing 5 ml of the free fatty acid concentrate plus 5 ml of a triacylglyerol concentrate containing 65% 3 fatty acids with eicosapentaenoic acid and docosahexaenoic acid composing 34.0% and 23.6% of that total, respectively. In seven of eight animal the infusion of the fish oil emulsion completely prevented the acute occurrence of VF in the susceptible animals (P < 0.005). In five of five of these animals the subsequent exercise-plus-ischemia test after a similar infusion of an emulsion in which soy bean oil replaced the fish oil fatty acid concentrates resulted in prompt development of VF. Possible mechanisms for this protective effect of 3 fatty acids against exercise and ischemia-induced malignant arrhythmias are considered.From their studies among the Greenland Inuits Bang et al. (1) suggested the possibility that the low mortality rates among the natives from coronary heart disease (CHD) resulted from their high intake of long-chain polyunsaturated fatty acids of the O3 class derived from ingestion of large amounts of marine vertebrates in their diet. Since these pioneering observations many studies have been reported in animals and humans on the effects ofingestion offish and fish oils on CHD. Most, but not all, of the animal studies have demonstrated beneficial effects on experimental atherosclerosis. In the laboratory the 3 fatty acids seem to increase the production by cells of humans and animals of some antiatherogenic factors and reduce the activity of many proatherogenic factors (for review, see ref.2). In humans the prevention of CHD mortality by w3 fatty acid ingestion is strongly supported by epidemiologic studies (3), but there are still very few prospective, randomized, doubleblind, placebo-controlled clinical trials to determine whether CHD can, in fact, be prevented by intake of 3 fatty acids. Furthermore, because the epidemiologic stu...

Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons.

“…The strength of the effect of the fatty acids on voltage dependence increases with the number of C=C unsaturated bonds. Since esterified PUFAs were without effect in vitro (9) and in vivo (15), the apparent structural requirements for affecting INa have been proposed to be a long hydrocarbon chain with two or more unsaturated C=C bonds and a free carboxylic acid group at one end (23).…”

“…Diets enriched with fish oils or n-3 fatty acids prevented fatal ventricular arrhythmias in rats (10,11) and probably in humans (12)(13)(14). Furthermore, infusion of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intravenously just before an ischemic event prevented ventricular fibrillation in exercising dogs (15).…”

Suppression of voltage-gated L-type Ca 2+ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes

“…protective antiarrhythmic effect of ingestion of fish or fish oil has been shown to be attributable to their eicosapentaenoic acid (EPA; C20:5 n Ϫ 3) and docosahexaenoic acid (C22:6 n Ϫ 3) content as demonstrated by administering a highly concentrated fish oil preparation of free n Ϫ 3 PUFAs intravenously just before the ischemic challenge and preventing the fatal arrhythmias (4). But studies with isolated cultured neonatal rat cardiac myocytes showed that polyunsaturated fatty acids, both n Ϫ 6 and n Ϫ 3, are antiarrhythmic during Ca 2ϩ overload (8).…”

The effect of acute simvastatin administration on the severity of arrhythmias resulting from ischaemia and reperfusion in the canine: Is there a role for nitric oxide?

“…Certainly, long-term statin treatment by modulating the lipid portions of the sarcolemma, which contain the ion channel regulatory proteins and signalling molecules (lipid rafts), influence the ion channel conduction and ion transport (Maguy et al, 2006;Vyas et al, 2006), but it is not known whether such a mechanism would also account for the acute administration of statins. Nevertheless, considering that polyunsaturated fatty acids, which alter the structure of the sarcolemmal phospholipids, were able to evoke immediate antiarrhythmic effect (Billman et al, 1994;Kang and Leaf, 2000;Leaf et al, 2003), we may speculate that statins perhaps also possess such acute modulator properties on the lipid portions of the membrane. This, by causing favourable changes in ion transport or by stabilizing the membrane, would lead to arrhythmia suppression during ischaemia.…”