Toxic properties of arachidonic acid on normal, ischemic and reperfused hearts. Indirect evidence for free radical involvement.
We studied the effect of arachidonic acid on function and CPK release of normal, ischemic and reperfused isolated rat hearts. Under control conditions arachidonate (10 micrograms/ml) produced a transient inotropic effect which gradually reversed during a 90 minute perfusion. Creatinephosphokinase (CPK) release was augmented by arachidonic acid, particularly under high flow (pre-ischemia and reperfusion) conditions. Recovery of contractility following reperfusion of ischemic myocardium was significantly depressed by arachidonic acid. Vitamin E (100 ng/ml) an antioxidant and free radical scavenger, reduced the enzyme leakage and enhanced recovery of contractility of reperfused myocardium. It also prevented the depression in contractility during control perfusion. Similar protective effects were observed by perfusing the heart with reduced calcium but not by nifedipine; a calcium channel blocker, indomethacin; a prostaglandin synthesis inhibitor or nordihydroguarietic acid; a lipoxygenase inhibitor. Arachidonic acid also inhibited membrane Na+/K+-ATPase although it is unlikely that this property mediated its cardiotoxic influence since it was not prevented by vitamin E. In addition, we observed that arachidonic acid increased the coronary resistance of isolated hearts, probably through enhanced calcium influx as this constriction was reduced by low calcium as well as by nifedipine. Thus, arachidonic acid possesses distinct properties. Its cardiotoxic influence is likely mediated by free radical generation.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D003402:Creatine Kinase; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D005609:Free Radicals; D016718:Arachidonic Acid; D003402:Creatine Kinase; D007213:Indomethacin