ANTIARRHYTHMIC EFFECTS OF EICOSAPENTAENOIC ACID DURING MYOCARDIAL-INFARCTION - ENHANCED CARDIAC MICROSOMAL (CA2-MG2+)-ATPASE ACTIVITY()

The effects of dietary supplementation with eicosapentaenoic acid (EPA ) on ventricular arrhythmias during myocardial infarction were examine d in a canine model. EPA was incorporated into cellular membranes afte r ingestion of EPA-ester (100 mg/kg body weight/day) for 8 weeks. The ratio of EPA to arachidonic acid (AA) in platelet cell membranes and m yocardial microsomes was significantly increased (7% to 37% in platele t cell membranes; p<0.01, 3% to 12% in non-infarcted cardiac microsome s; p<0.01, and from 2% to 8% in infarcted cardiac microsomes; p<0.01). Dietary supplementation with EPA significantly reduced the incidence and severity of arrhythmias during coronary artery occlusion. Immediat ely after coronary artery occlusion, all of the animals in the control group that were given a toxic dose of digitalis developed ventricular tachycardia (VT) or ventricular fibrillation (Vf), whereas none of th e animals in the EPA-supplement group developed VT or Vf within 15 min after administration of digitalis. Regardless of the presence of an i nfarcted area, the specific activity of the Ca2+-pump enzyme ((Ca2+-Mg 2+)-ATPase) within the myocardial microsomal fraction of the EPA-suppl emented group was significantly higher than in that of the control gro up (Vmax: 140.5+/-19.1 vs 94.8+/-28.9 nmol/mg/min in non-infarcted car diac microsomes, p<0.01, 130.9+/-18.4 vs 90.2+/-26.4 nmol/mg /min in i nfarcted cardiac microsomes, p<0.01, EPA vs control group, respectivel y). The specific activities of the Na+-pump enzyme ((Na+-K+)-ATPase) a nd NADPH-dependent cytochrome C reductase in infarcted and non-infarct ed cardiac microsomes did not differ between these groups. These resul ts indicate that EPA supplementation increases the (Ca2+-Mg2+)-ATPase activity within myocardial membranes that is involved in Ca2+ metaboli sm in myocardial cells by increasing the ratio of EPA to AA within cel lular membranes. These cellular alterations are likely to reduce the s everity of ventricular arrhythmias by inhibiting the rapid accumulatio n of intracellular Ca2+ following ischemia.