Effect of polymorphonuclear leukocyte-derived oxygen free radicals and hypochlorous acid on cardiac function and some biochemical parameters.
Polymorphonuclear (PMN) leukocyte activation is known to result in the production and release of oxygen free radicals and hypochlorous acid. Various clinical conditions are associated with PMN leukocyte stimulation. The present investigation deals with the effects of stimulated PMN leukocytes in the absence and in the presence of scavengers of oxygen free radicals (superoxide dismutase, catalase), hypochlorous acid quencher (methionine), and myeloperoxidase inhibitor (azide) on cardiac function and contractility; blood lactate, gases, and pH levels, blood and cardiac tissue malondialdehyde; and PMN leukocyte chemiluminescence activity in anesthetized dogs. Opsonised zymosan was used for stimulation of PMN leukocytes, and the effects were observed for 2 hours. The dogs were divided into four groups: group I, zymosan; group II, superoxide dismutase + catalase + zymosan; group III, methionine + zymosan; group IV, azide + methionine + zymosan. Zymosan produced a decrease in cardiac function and in indices of myocardial contractility and an increase in systemic and pulmonary vascular resistance. There was a decrease in blood pH and in PMN leukocyte chemiluminescense and an increase in the blood lactate and malondialdehyde. Superoxide dismutase plus catalase and methionine reduced the effect of zymosan on cardiac function and contractility and on blood malondialdehyde, lactate, and pH. The combination of azide and methionine did not prevent the deleterious effects of zymosan on cardiac function and contractility. Cardiac tissue malondialdehyde levels were lower in groups III and IV than in groups I and II which had values similar to each other. Methionine was superior to superoxide dismutase plus catalase in the prevention of the deleterious effects of PMN leukocyte stimulation on the various measured parameters. These results suggest that oxygen free radicals and hypochlorous acid are cardiac depressants and increase systemic and pulmonary vascular resistance in addition to causing tissue damage. Clinical situations with PMN stimulation may result in cardiac depression. The oxygen free radical scavenger and hypochlorous acid quencher may be beneficial in the counteraction of the deleterious effects of PMN leukocyte stimulation on the hemodynamic parameters and cellular integrity.
Prasad
K
K
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Kalra
J
J
Chaudhary
A K
AK
Debnath
D
D
D000818:Animals; D001386:Azides / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005609:Free Radicals; D006997:Hypochlorous Acid / Q000633:toxicity*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008213:Lymphocyte Activation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008715:Methionine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000633:toxicity*; D019810:Sodium Azide; D013482:Superoxide Dismutase / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D015054:Zymosan / Q000494:pharmacology
D001386:Azides; D005609:Free Radicals; D007773:Lactates; D019344:Lactic Acid; D008315:Malondialdehyde; D006997:Hypochlorous Acid; D015054:Zymosan; D019810:Sodium Azide; D008715:Methionine; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen