Oxygen free radicals and heart failure.
We hypothesize that oxygen free radicals are involved in the genesis and maintenance of volume and pressure overload heart failure. Pressure and volume overload would produce myocardial ischemia. During ischemia there will be an increase in xanthine and xanthine oxidase; and a decrease in the superoxide dismutase and glutathione peroxidase activity leading to an increase in the oxygen free radicals. A decrease in the cellular pH during ischemia would release phospholipase which would, in turn, release arachidonic acid from phospholipids. Leukotrienes and prostaglandins will be synthesized through arachidonic acid metabolism. During this synthesis not only oxygen free radicals 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 mechanism would also lead to an increase in the oxygen free radicals. Oxygen free radicals are known to depress Ca++ binding and uptake of sarcoplasmic reticulum which would lead to a decrease in the myocardial contractility. We have shown that oxygen free radicals depress cardiac function and cardiac contractility. 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 oxygen free radicals would be of value in the prevention and treatment of heart failure.
Prasad
K
K
Department of Physiology, University of Saskatchewan, College of Medicine, Saskatoon, Canada.
Kalra
J
J
D000818:Animals; D005609:Free Radicals; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D011453:Prostaglandins / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D005609:Free Radicals; D006878:Hydroxides; D011453:Prostaglandins; D013481:Superoxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide