We hypothesize that oxygen free radicals are involved in the genesis and maintenance of volume and pressure overload heart failure. Pressure and vol ume overload would produce myocardial ischemia. During ischemia there will be an increase in xanthine and xanthine oxidase; and a decrease in the superox ide dismutase and glutathione peroxidase activity leading to an increase in the oxygen free radicals. A decrease in the cellular pH during ischemia would re lease phospholipase which would, in turn, release arachidonic acid from phos pholipids. Leukotrienes and prostaglandins will be synthesized through arachidonic acid metabolism. During this synthesis not only oxygen free radi cals will be produced but also there will be formation of leukotriene, LTB4, which is known to activate neutrophil and hence increased secretion of oxygen free radicals. Increased circulatory catecholamines due to compensatory mech anism would also lead to an increase in the oxygen free radicals. Oxygen free radicals are known to depress Ca++ binding and uptake of sarcoplasmic retic ulum which would lead to a decrease in the myocardial contractility. We have shown that oxygen free radicals depress cardiac function and cardiac contractil ity. It is, therefore, suggested that oxygen free radicals might be involved in the development of heart failure. The use of agents that reduce the amount of oxy gen free radicals would be of value in the prevention and treatment of heart failure.
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