Effects of dietary omega–3 fatty acids on ventricular function in dogs with healed myocardial infarctions: in vivo and in vitro studies

Abstract

Since omega-3 polyunsaturated fatty acids (n-3 PUFAs) can alter ventricular myocyte calcium handling, these fatty acids could adversely affect cardiac contractile function, particularly following myocardial infarction. Therefore, 4 wk after myocardial infarction, dogs were randomly assigned to either placebo (corn oil, 1 g/day, n = 16) or n-3 PUFAs supplement [docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) ethyl esters; 1, 2, or 4 g/day; n = 7, 8, and 12, respectively] groups. In vivo, ventricular function was evaluated by echocardiography before and after 3 mo of treatment. At the end of the 3-mo period, hearts were removed and in vitro function was evaluated using right ventricular trabeculae and isolated left ventricular myocytes. The treatment elicited significant (P < 0.0001) dose-dependent increases (16.4-fold increase with 4 g/day) in left ventricular tissue and red blood cell n-3 PUFA levels (EPA + DHA, placebo, 0.42 +/- 0.04; 1 g/day, 3.02 +/- 0.23; 2 g/day, 3.63 +/- 0.17; and 4 g/day, 6.97 +/- 0.33%). Regardless of the dose, n-3 PUFA treatment did not alter ventricular function in the intact animal (e.g., 4 g/day, fractional shortening: pre, 42.9 +/- 1.6 vs. post, 40.1 +/- 1.7%; placebo: pre, 39.2 +/- 1.3 vs. post, 38.4 +/- 1.6%). The developed force per cross-sectional area, changes in length- and frequency-dependent behavior in contractile force, and the inotropic response to beta-adrenoceptor activation were also similar for trabeculae obtained from placebo- or n-3 PUFA-treated dogs. Finally, calcium currents and calcium transients were the same in myocytes from n-3 PUFA- and placebo-treated dogs. Thus dietary n-3 PUFAs did not adversely alter either in vitro or in vivo ventricular contractile function in dogs with healed infarctions.

Effects of omacor&lt;sup&gt;&#174; &lt;/sup&gt;on left ventricular remodelling consecutive to post myocardial infarction special issue-myocardial infarction

“…This cardioprotection mediated by OMACOR ® was associated with a partial reduction of the collagen scar suggesting that the compound could preserve the remodelling of heart tissue consecutively to myocardial infarction. Our findings that OMACOR ® reduces left ventricular dilation after myocardial infarction are in agreement with previous findings demonstrating that PUFAs reduce heart failure induced by myocardial infarction in dog [14], as well as in rat with left ventricular pressure overload [13]. These protective effects of OMACOR ® on post myocardial infarction induced ventricular dysfunction are associated with a decrease of myocardial remodelling and alterations of Cx43 phosphorylation.…”

Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Supplementation Reduces Vulnerability to Atrial Fibrillation

“…14 The levels of integration observed in this study are comparable with other studies of PUFA supplementation in dogs. 15 Had we supplemented for a longer duration it is likely that there would have been a small increase in PUFA levels. 15 It is notable that DHA supplementation increased plasma EPA, possibly indicative of retroconversion of DHA to EPA; this also has been observed previously.…”

Omega-3 fatty acids: antiarrhythmic, proarrhythmic or both?

“…Dogs were subjected to an experimental myocardial infarction, and 4 weeks later randomized to receive omega-3 fatty acids or placebo for 3 months. Ventricular function was then assessed in a number of ways, but no differences were found (Billman et al, 2010). Size of an experimental infarction was smaller in rats given omega-3 fatty acids than diets rich in saturated or omega-6 fatty acids (Zeghichi-Hamri et al, 2010).…”