It is now clear that oxygen-derived free radicals play an important part in several models of experimentally induced reperfusion injury. Although there are certainly multiple components to clinical ischemic and reperfusion injury, it appears likely that free-radical production may make a major contribution at certain stages in the progression of the injury. The primary source of superoxide in reperfused reoxygenated tissues appears to be the enzyme xanthine oxidase, released during ischemia by a calcium-triggered proteolytic attack on xanthine dehydrogenase. Reperfused tissues are protected in a variety of laboratory models by scavengers of superoxide radicals or hydroxyl radicals or by allopurinol or other inhibitors of xanthine oxidase. Dysfunction induced by free radicals may thus be a major component of ischemic diseases of the heart, bowel, liver, kidney, and brain.

Oxygen-derived free radicals in postischemic tissue injury.

ObjectivesIn view of the critical role of intracellular Ca2+-overload in the genesis of myocyte dysfunction and the ability of reactive oxygen species (ROS) to induce the intracellular Ca2+-overload, this article is concerned with analysis of the existing literature with respect to the role of oxida

Role of oxidative stress in cardiovascular diseases.

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Myocardial reperfusion: a double-edged sword?

Therapy directed against the toxic effects of reactive oxygen species may reduce the final extent of ischemic injury in otherwise viable tissue irreversibly injured by the abrupt reoxygenation of reperfusion. In four groups of dogs, superoxide dismutase plus catalase (groups I-III) or saline (controls) (group IV) was infused into the left atrium. Group I received the infusion for 2 hours, beginning 15 minutes before occlusion of the left circumflex coronary artery (90 minutes) and ending 15 minutes after reperfusion. Group II received the infusion for 1 hour starting 15 minutes before reperfusion. Group III received the infusion for 1 hour beginning 40 minutes after reperfusion. Dogs were killed the next day, and infarct size was determined by dissection and weighing, and confirmed histologically. Infarct size expressed as percent of the anatomic area at risk was: group I, 19.4 +/- 5.0; group II, 21.8 +/- 3.3; group III, 47.6 +/- 10.3; group IV, 43.6 +/- 3.5 (mean +/- SEM). Analysis of variance followed by Duncan's multiple range test showed that ultimate infarct size as assessed in groups I and II differed significantly (P less than 0.05) from that observed in the control animals in group IV, whereas infarct size between groups III and IV did not differ significantly (P greater than 0.05). The percent of left ventricle at risk did not differ between the four groups. The beneficial effects of superoxide dismutase plus catalase could not be explained by hemodynamic differences. Similar protection of jeopardized myocardium in groups I and II suggest that potentially viable tissue is salvaged by scavenging free radicals during early reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase.

Xanthine oxidase as a source of free radical damage in myocardial ischemia.

A working hypothesis on pathogenesis of ischemic heart damage has been proposed. According to this hypothesis, a crucial role in conversion of reversible damage into irreversible damage is played by cardiomyocyte membrane destruction caused by the so-called “lipid triad”. The latter comprises activation of lipid peroxidation, activation of phospholipases, and the degergentlike action of excessive amounts of free fatty acids and lysophospholipids. Marked activation of lipid peroxidation in experimental myocardial infarction, as well as reoxygenation following transitory ischemia, have been demonstrated. The proposed hypothesis and experimental data underly successful application of synthetic free radical scavengers (antioxidants) for heart protection against experimental myocardial infarction, transitory ischemia, and emotional, painful stress.

Kozlov YuP

Papers

The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart.