SUMMARY. 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 starring 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 < 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 > 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. Lack of protection in group III suggests that injury has occurred within the first 40 minutes of reperfusion. The results of this investigation demonstrate that the '"primary' myqcardial cellular damage due to ischemia is additive to the cardiac cell damage during the phase of reperfusion, and that the "secondary" effects are mediated by toxic metabolites of oxygen. (Che Res 54: 277-285, 1984)

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Experiments were performed in the dog to examine the effects of neutropenia on ultimate infarct size resulting from short (90 minutes) or prolonged (4 hours) circumflex coronary artery occlusion. Sheep antiserum to canine neutrophils was used to produce neutropenia. Control animals received nonimmune serum. Neutrophil infiltration into myocardial infarcts was examined using histopathologic techniques and a semiquantitative scoring system. In 90-minute occlusions with 24-hour reperfusion, neutropenia was associated with the development of significantly smaller infarcts: normopenic group, 43.2% +/- 3.3% (n = 7) vs. neutropenic group, 26.6% +/- 3.7% (n = 10) of the area at risk, means +/- SEM. However, in 4-hour occlusion with 6-hour reperfusion experiments, the tendency of neutrophil depletion to reduce infarct size did not reach statistical significance (46.4% +/- 7.2% vs. 31.5% +/- 6.0% of the area at risk, normopenic vs. neutropenic) despite differences in neutrophil infiltration into the reperfused region. The observed differences in ultimate infarct size could not be attributed to differences in myocardial oxygen consumption. The results suggest that a significant amount of myocardial infarction induced by a limited duration of coronary artery occlusion followed by reperfusion is neutrophil dependent and appears to be less important in determining the fate of myocardium subjected to more prolonged periods of ischemia followed by reperfusion.

Patients with end-stage renal disease often demonstrate retarded healing of surgical wounds, but the basis for spontaneous wound formation in these patients is less well understood. We report our experience with four patients with a unique clinical entity previously described as the uremic gangrene syndrome (also known as calciphylaxis) that involves spontaneously forming and insidiously progressive wounds of the skin and soft tissue in uremic patients with hyperparathyroidism. The importance of recognizing this phenomenon relates to the potential benefit to wound-healing efforts resulting from subtotal parathyroidectomy and adjustment of serum calcium and phosphate levels when severe hyperparathyroidism is present. Disrupted parathyroid homeostasis as a mechanism for soft-tissue ischemia and subsequent infarction is supported by wound biopsies demonstrating microarterial calcification. As experts in factors resulting in refractory wounds, plastic surgeons need be aware of this peculiar vulnerability for spontaneously forming wounds in uremic patients. Clinical and laboratory findings, success with wound treatment in four patients, and currently popular pathophysiologic mechanisms are discussed.

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