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Clinically and experimentally, a case for omega-3 polyunsaturated fatty acid (PUFA) cardioprotection in females has not been clearly established. The goal of this study was to investigate whether dietary omega-3 PUFA supplementation could provide ischemic protection in female mice with an underlying genetic predisposition to cardiac hypertrophy. Mature female transgenic mice (TG) with cardiac-specific overexpression of angiotensinogen that develop normotensive cardiac hypertrophy and littermate wild-type (WT) mice were fed a fish oil-derived diet (FO) or PUFA-matched control diet (CTR) for 4 wk. Myocardial membrane lipids, ex vivo cardiac performance (intraventricular balloon) after global no-flow ischemia and reperfusion (15/30 min), and reperfusion arrhythmia incidence were assessed. FO diet suppressed cardiac growth by 5% and 10% in WT and TG, respectively (P < 0.001). The extent of mechanical recovery [rate-pressure product (RPP) = beats/min x mmHg] of FO-fed WT and TG hearts was similar (50 [+ or -] 7% vs. 45 [+ or -] 12%, 30 min reperfusion), and this was not significantly different from CTR-fed WT or TG. To evaluate whether systemic estrogen was masking a protective effect of the FO diet, the responses of ovariectomized (OVX) WT and TG mice to FO dietary intervention were assessed. The extent of mechanical recovery of FO-fed OVX WT and TG (RPP, 50 [+ or -] 4% vs. 64 [+ or -] 8%) was not enhanced compared with CTR-fed mice (RPP, 60 [+ or -] 11% vs. 80 [+ or -] 8%, P = 0.335). Dietary FO did not suppress the incidence of reperfusion arrhythmias in WT or TG hearts (ovary-intact mice or OVX). Our findings indicate a lack of cardioprotective effect of dietary FO in females, determined by assessment of mechanical and arrhythmic activity postischemia in a murine ex vivo heart model. polyunsaturated fatty acids; ischemia-reperfusion; Langendorff perfused hearts

Ischemic preconditioning (IPC) and (n-3) PUFA are both cardioprotective. This study compared effects of dietary fish oil, IPC, and their interactions on heart function and injury during myocardial ischemia and reperfusion. Male Wistar rats were fed diets containing 10% wt:wt fat comprising either 7% high-docosahexaenoic acid (DHA) [22:6(n-3)] tuna fish oil + 3% olive oil [(n-3) PUFA]; 5% sunflower seed oil + 5% olive oil [(n-6) PUFA]; or 7% beef tallow + 3% olive oil [saturated fat (SF)] for 6 wk. In control experiments, isolated perfused hearts were subjected to 30-min regional ischemia and reperfused for 120 min. The IPC hearts were subjected to 3 cycles of 5-min global ischemia before the ischemia and reperfusion. Control (n-3) PUFA hearts had significantly lower heart rate, coronary flow, end diastolic pressure, maximum relaxation rate, and ischemic and reperfusion arrhythmias. In reperfusion, they had greater developed pressure and maximum relaxation rate and smaller infarct (10.9 [+ or -] 0.6% ischemic zone, n = 6) than (n-6) PUFA (47.4 [+ or -] 0.3%, n = 6) or SF (50.3 [+ or -] 0.3%, n = 6). Compared with control, IPC significantly improved heart function and reduced infarct in (n-6) PUFA (11.8 [+ or -] 0.4%, n = 6) and SF hearts (13.1 [+ or -] 0.1%, n = 6). Heart function and infarct [(n-3) PUFA 9.6 [+ or -] 0.1%, n = 6] did not differ among dietary IPC groups. Arrhythmias, significantly reduced by IPC in (n-6) PUFA and SF hearts, were significantly lower in (n-3) PUFA IPC hearts. Dietary fish oil induces a form of preconditioning, nutritional preconditioning, limiting ischemic cardiac injury, and myocardial infarction and endows cardioprotection as powerful as IPC, which provides no additional protection in (n-3) PUFA hearts.

Fish oil (FO) modifies cardiac membrane phospholipid fatty acid composition to confer increased efficiency of oxygen utilization and antiarrhythmic effects. We tested the capacity of low-dose increments of FO, rich in (n-3) PUFA, to reverse the detrimental pro-arrhythmic and inefficient oxygen usage effects of dietary saturated fat (SAT) [including high ratio of (n-6) PUFA:(n-3) PUFA] during ischemia and reperfusion. Wistar rats were fed an SAT-enriched diet (15.3% fat, including 12% SAT, added by weight) for 6 wk and were then divided into 4 groups (n = 10/group) fed that diet or a 12% fat diet containing 3, 6, or 12% FO in place of SAT for 6 wk. Paced (300/min), erythrocyte-perfused isolated working hearts were subjected to low coronary flow ischemia (15 min) and were then reperfused. At normoxic baseline, external work capacity increased marginally at 6 and 12% FO; however, marked dose-related reductions in oxygen consumption were evident due to FO-dependent reduction in oxygen-energy utilization efficiency and associated reductions in coronary flow and oxygen extraction. Postischemic recovery resulted in lower oxygen consumption, greater oxygen-energy utilization efficiency, reduced coronary release of creatine kinase, and reduced incidence of arrhythmias in all FO groups compared with the SAT group. FO at a dose as low as 3% of total fat dietary supplement effectively reversed the high oxygen requirements and pro-arrhythmic effects of a SAT-rich diet even with continued consumption of SAT (9%) in this ex vivo animal model.

This study tested the hypothesis that in vivo antiarrhythmic effects of dietary fish oil can be attributed directly to changes in myocardial properties. Sixty adult male rats were fed a fish oil diet (FO), an isoenergetic saturated fat diet (SAT) or a low fat reference diet (REF) for 16 wk. hearts isolated from these rats were perfused with washed porcine erythrocytes (0.4 hematocrit) in working heart mode. Dietary fish oil prevented reperfusion-induced ventricular fibrillation (VF) (% of rats with VF: REF 50%, SAT 80% P = 0.35, FO 0% P < 0.05 n = 10) and reduced arrhythmias in ischemia. In a separate set of hearts from rats fed the three diets, FO increased while SAT reduced the stimulation threshold for programmed electrical induction of VF during control perfusion compared with REF (mean [+ or -] SD: REF 7.1 [+ or -] 0.2 mA; SAT 5.8 [+ or -] 0.2 mA, P < 0.001; FO 15.1 [+ or -] 1.0 mA, P < 0.001, n = 10) and during subsequent ischemia (REF 5.9 [+ or -] 0.2 mA; SAT 3.8 [+ or -] 0.3 mA, P < 0.001; FO 8.9 [+ or -] 0.2 mA, P < 0.001, n = 10). The isolated working heart model used physiological workload and oxygenation but excluded extracardiac influences. Dietary fish oil prevented the initiation and reduced the severity of arrhythmias in the isolated hearts in response to a variety of stimuli. These results establish that irrespective of any effects on blood pressure or platelet function in vivo, dietary fish oil directly affects myocardial properties which may contribute to observed clinical reductions in cardiac mortality associated with fish consumption. INDEXING KEY WORDS: dietary fats (n-3) fatty acids; myocardial ischemia; arrhythmia; rats

Previous research showed that dietary fish oil was potently antiarrhythmic in rats but olive oil was not. This study was designed to test the hypothesis that canola oil, another major dietary source of oleic acid additionally containing the (n-3) polyunsaturated fatty acid [Alpha]-linolenic acid [18:3(n-3)], can reduce vulnerability to cardiac arrhythmia in rats. Rats were randomly assigned to one of four experimental diet groups for 12 wk. The fat source in the diets was 12% olive (63% oleic acid), canola (55% oleic, 8% [Alpha]-linolenic acid), soybean [50% linoleic 18:2(n-6), 7% [Alpha]-linolenic acid] or sunflower seed oil (64% linoleic acid). Arrhythmias were induced by coronary artery occlusion and reperfusion. Incidence of ventricular fibrillation, mortality and arrhythmia score during reperfusion were significantly lower in rats fed the diet containing canola oil than in those fed the olive oil diet. No difference in the severity of arrhythmias was seen in groups fed diets containing soybean or sunflower seed oils. Analysis of myocardial phospholipid fatty acids showed that consumption of canola oil decreased the ratio of (n-6)/(n-3) polyunsaturated fatty acids relative to the other diets, as does dietary fish oil. These results suggest that regular substitution of canola oil for other dietary lipid sources may assist in reducing the likelihood of a transient ischemic event leading to life-threatening cardiac arrhythmias, but the effectiveness of [Alpha]-linolenic acid is reduced by high levels of linoleic acid. INDEXING KEY WORDS: reperfusion; (n-3) fatty acids; canola; arrhythmia; [Alpha]-linolenic acid; rats

A study was conducted to evaluate the effects of different protein sources like whey, soy, red meat and milk protein on energy intake and body weight maintenance in chronic diet-induced obese mice. Results indicated that though dietary fat remained a major factor in weight management, the type and amount of protein intake also affected weight.