Myocardial damage due to ischemia and reperfusion in hypertriglyceridemic and hypertensive rats: participation of free radicals and calcium overload

Objective In a model of hypertriglyceridemia and hypertension in rats (HTG) , induced by adding refined sugar to the animals' drinking water, we invest igated the response to an acute stress, such as ischemia and reperfusion, I n addition, we examined the contribution of calcium overload and free radic al release to the injury caused by the post-ischemic reperfusion in a patho logical state compared with the normal state. Methods Ischemia was induced in the whole anaesthetized animal, by occlusio n of the left coronary artery for 4 min, followed by reperfusion for 6 min. To prevent either calcium overload or lipid oxidative processes during rep erfusion, either Ketorolac (KET), a calcium ionophore-like drug, or alpha-P henyl-N-ter-butyl nitrone (PBN), a spin-trapping agent, was administered be forehand. Results Ketorolac failed to protect the HTG animals from heart damage, as s een by the incidence of reperfusion dysrhythmias, release of lactate dehydr ogenase and creatine kinase to the plasma, and non-recovery of the sinus rh ythm. On the other hand, PEN was able to prevent these harmful events in th e HTG heart by diminishing lipoperoxidation, Conclusions The results suggest that, in HTG animals, the oxidative process es make a major contribution to the reperfusion injury and that the sole pr otection from calcium overload provided by KET is not sufficient to avoid d amage compared with control rats. (C) Lippincott Williams & Wilkins.