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Effect of polymorphonuclear leukocyte-derived oxygen free radicals and hypochlorous acid on cardiac function and some
K Prasad1, J Kalra, A K Chaudhary
1Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Abstract:
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.
Insights
Polymorphonuclear leukocyte activation harms cardiac function by releasing damaging oxygen free radicals and hypochlorous acid. Methionine effectively counteracted these effects, suggesting its therapeutic potential.
Area of Science:
- Cardiovascular Physiology
- Immunology
- Biochemistry
Background:
- Polymorphonuclear (PMN) leukocyte activation generates oxygen free radicals and hypochlorous acid.
- These reactive species are implicated in various clinical conditions involving PMN stimulation.
- Understanding their impact on cardiac function is crucial for clinical management.
Purpose of the Study:
- To investigate the effects of stimulated PMN leukocytes on cardiac function and hemodynamics.
- To evaluate the protective roles of oxygen free radical scavengers and hypochlorous acid quenchers.
- To assess the efficacy of superoxide dismutase, catalase, methionine, and azide in mitigating PMN-induced damage.
Main Methods:
- Anesthetized dogs were stimulated with opsonized zymosan to activate PMN leukocytes.
- Groups received zymosan alone or in combination with scavengers/inhibitors (superoxide dismutase + catalase, methionine, azide + methionine).
- Cardiac function, contractility, blood lactate, gases, pH, and malondialdehyde levels were measured over 2 hours.
Main Results:
- Zymosan-induced PMN activation decreased cardiac function and contractility, increasing vascular resistance, blood lactate, and malondialdehyde, while decreasing blood pH.
- Superoxide dismutase plus catalase and methionine attenuated these deleterious effects on cardiac function and biochemical markers.
- Methionine demonstrated superior protection compared to superoxide dismutase plus catalase in preventing PMN-induced cardiac depression and tissue damage.
Conclusions:
- Oxygen free radicals and hypochlorous acid produced by activated PMN leukocytes are potent cardiac depressants and contribute to tissue damage.
- PMN leukocyte stimulation can lead to significant cardiac depression in clinical settings.
- Oxygen free radical scavengers and hypochlorous acid quenchers, particularly methionine, show promise in counteracting PMN-induced cardiovascular and cellular injury.