Dietary fish oil prevents reperfusion Ins(1,4,5)P₃ release in rat heart: Possible antiarrhythmic mechanism

Dietary enrichment with fish oil-derived n-3 polyunsaturated fatty acids has been shown to suppress the arrhythmias that occur during postischemic reperfusion. We have recently implicated a rapid release of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P₃] during postischemic reperfusion in the generation of these arrhythmias. The effects of dietary supplementation with fish oil on both cardiac Ins(1,4,5)P₃ and arrhythmogenic responses to reperfusion were therefore investigated in perfused rat hearts. Comparisons were made with control and n-6 polyunsaturated or saturated fat-supplemented diets. In control hearts, reperfusion increased Ins(1,4,5)P₃ levels [from 9 ± 2 at 20 min ischemia to 26 ± 3 counts per minute (cpm)/mg protein with 2 min of reperfusion] and produced a high incidence of ventricular tachycardia (92% VT) and ventricular fibrillation (85% VF). Dietary fish oil supplementation, which increased composition of n-3 fatty acids in myocardial membrane phospholipids, prevented the reperfusion-induced rise in Ins(1,4,5)P₃ (11 ± 1 at 20 min ischemia and 12 ± 2 cpm/mg protein after 2- min reperfusion) and significantly suppressed reperfusion arrhythmias (38% VT, 13% VF; P < 0.01 vs. control group). Thus the inhibition of reperfusion- induced rises in Ins(1,4,5)P₃ by n-3 polyunsaturated fatty acids after dietary fish oil supplementation provides a possible mechanism for the inhibitory effect of n-3 fatty acids on reperfusion-induced arrhythmias.