The lipid mediator 4(RS)-4-F4t-neuroprostane derived from non-enzymatic peroxidation of DHA contributes to cardioprotective properties of this PUFA following an ischemia/reperfusion event. 4(RS)-4-F4tneuroprostane displays a strong anti-apoptotic property involving the normalization of calcium homeostasis by the stabilization of ryanodine receptor complex and to a decrease of mPTP opening leading to the reduction of pro-apoptotic factors. This study suggests that some well-known effects of n-3 fatty acids are mediated by their non-enzymatic cyclic oxygenated metabolites. This discovery opens new perspectives for non-enzymatic oxidized products of n-3 polyunsaturated fatty acids as potent preventive therapeutic way in acute myocardial infarction.