This study compared monounsaturated oleic acid with n−6 and n−3 polyunsaturated fatty acids (PUFAs) for their ability to modify the vulnerability to cardiac arrhythmias during ischemia or reperfusion in rats. Replacement of saturated animal fat in the diet with oleic acid-rich olive oil did not significantly alter the incidence of ventricular fibrillation or other cardiac arrhythmias. Replacement with either n−6-rich sunflower seed oil or n−3-rich fish oil reduced the incidence and severity of arrhythmias occurring in ischemia. The fish oil significantly reduced reperfusion arrhythmias independently of antecedent ischemic arrhythmias. Fatal ventricular fibrillation was significantly reduced by n−6 (8%; n = 25) and n−3 (0%; n = 24) PUFA but not by monounsaturates (36%; n = 25) compared with saturated fat (42%; n = 24). The results suggest that dietary replacement of saturated fats by n−6 and especially n−3 PUFA but not monounsaturated fatty acids can reduce the likelihood of an ischemic event leading to sudden cardiac death.

Background — Regular fish consumption is associated with low cardiovascular disease morbidity and mortality. Fish oils modify cardiac membrane phospholipid fatty acid composition with potent antiarrhythmic effects. We tested the effects of dietary fish oil on ventricular hemodynamics and myocardial oxygen consumption (MVO ₂ ). Methods and Results — Male Wistar rats were fed for 16 weeks on a reference diet rich in n -6 polyunsaturated fatty acids (PUFA), a diet rich in saturated animal fat (SAT), or a diet rich in n -3 PUFA from fish oil. Isolated working hearts were perfused with porcine erythrocytes (40% hematocrit) at 75 mm Hg afterload with variable preload (5 to 20 mm Hg) or with low coronary flow ischemia with maintained afterload, preload, and heart rate, then reperfused. MVO ₂ was low and coronary perfusion reserve high in n -3 PUFA hearts, and cardiac output increased with workload. The n -3 PUFA reduced ischemic markers—acidosis, K ⁺ , lactate, and creatine kinase—and increased contractile recovery during reperfusion. SAT hearts had high MVO ₂ , low coronary perfusion reserve, and poor contractile function and recovery. Dietary differences in MVO ₂ were abolished by KCl arrest (basal metabolism) or ruthenium red (3.4 μmol/L) but not by ryanodine (1 nmol/L). Fish oil or ryanodine, but not ruthenium red, prevented ventricular fibrillation in reperfusion. Conclusions — Dietary fish oil directly influenced heart function and improved cardiac responses to ischemia and reperfusion. The n -3 PUFA reduced oxygen consumption at any given work output and increased postischemic recovery. Thus, direct effects on myocardial function may contribute to the altered cardiovascular disease profile associated with fish consumption.

Dietary omega-3 polyunsaturated fatty acids (PUFAs) are readily incorporated into heart and skeletal muscle membranes where, in the heart, animal studies show they reduce O2 consumption. To test the hypothesis that omega-3 PUFAs alter O2 efficiency in humans, the effects of fish oil (FO) supplementation on O2 consumption during exercise were evaluated. Sixteen well-trained men (cyclists), randomly assigned to receive 8 x 1 g capsules per day of olive oil (control) or FO for 8 weeks in a double-blind, parallel design, completed the study (control: n = 7, age 27.1 +/- 2.7 years; FO: n = 9, age 23.2 +/- 1.2 years). Subjects used an electronically braked cycle ergometer to complete peak O2 consumption tests (VO 2peak) and sustained submaximal exercise tests at 55% of peak workload (from the VO 2peak test) before and after supplementation. Whole-body O2 consumption and indirect measurements of myocardial O2 consumption [heart rate and rate pressure product (RPP)] were assessed. FO supplementation increased omega-3 PUFA content of erythrocyte cell membranes. There were no differences in VO 2peak (mL kg(-1) min(-1)) (control: pre 66.8 +/- 2.4, post 67.2 +/- 2.3; FO: pre 68.3 +/- 1.4, post 67.2 +/- 1.2) or peak workload after supplementation. The FO supplementation lowered heart rate (including peak heart rate) during incremental workloads to exhaustion (P < 0.05). In addition, the FO supplementation lowered steady-state submaximal exercise heart rate, whole-body O2 consumption, and RPP (P < 0.01). Time to voluntary fatigue was not altered by FO supplementation. This study indicates that FOs may act within the healthy heart and skeletal muscle to reduce both whole-body and myocardial O2 demand during exercise, without a decrement in performance.