SUMMARY Accumulation of polymorphonuclear neutrophils during the acute inflammatory response may exacerbate tissue injury through the release of activated oxygen products or proteolytic enzymes or both. To assess the role of neutrophils in acute myocardial infarction, circulating neutrophil levels in dogs were reduced by 77 + 2% (mean SEM) by administering rabbit antiserum to dog neutrophils. Acute myocardial infarction was induced in open-chest anesthetized dogs by 90 minutes of left circumflex coronary artery occlusion followed by 6 hours of reperfusion. Dogs treated with neutrophil antiserum (n = 8) developed myocardial infarcts that were an average of 43% smaller' than infarcts in dogs treated with nonimmune rabbit serum (n = 7) (27.0 ± 4.5% vs 47.1% 7.5% of the area at risk, p < 0.05). In a salinetreated control group (n = 8), infarct size was 48.0 ± 4.7% of the area at risk, a value not significantly different from that of the nonimmune serum group but significantly greater than that in the neutrophil antiserum dogs (p < 0.05). There were no major hemodynamic differences between groups. Histopathologic examination revealed that infarcted myocardium from dogs given saline or treated with nonimmune serum had a substantial neutrophilic infiltrate, which was virtually absent in infarcted tissue from dogs treated with neutrophil, antiserum. These observations suggest that neutrophil accumulation in response to myocardial ischemia may be responsible for a substantial portion of the irreversible myocardial' injury resulting from temporary coronary artery occlusion.THE MIGRATION of polymorphonuclear neutrophils into recently infarcted myocardium represents the initial phase of a process that leads to demolition and subsequent organization of injured tissue and culminates in the replacement of necrotic myocardium with fibrous scar." 2 Infiltration of neutrophils into irreversibly injured myocardium facilitates the breakdown of necrotic myocardium, which promotes resorbtion or phagocytosis by macrophages.2 After the removal of tissue debris, capillaries and fibroblasts invade the infarcted area and lead to the formation of collagen-rich scar tissue, which replaces the necrotic area.2 During the early acute inflammatory response, polymorphonuclear neutrophils undergo a complex series of functional and biochemical alterations that promote tissue lysis. Although these events are important to the repair process, they may also result in the destruction of potentially viable tissue elements. Stimulated neutrophils release highly reactive and cytotoxic activated oxygen species such as superoxide anion, hydroxyl radical, hydrogen peroxide and singlet oxygen. These activated oxygen radicals degrade extracellular macromolecules, attack membrane phospholipids and, thus, promote cell injury or death. idonic acid, which is converted by specific lipoxygenases to potent chemotactic hydroxy-eicosatetraenoic acids (HETEs).6 These chemoattractant substances promote the further recruitment of neutrophils into the acute inflammatory re...

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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Adhesion of vibrios to the small intestine may occur (i) by association of the bacteria with secreted mucus gel or (ii) by adherence of the bacteria to the surface of epithelial cells. In the present study, vibrios readily adhered to isolated brush border membranes obtained from rabbit intestinal epithelial cells. Adhesion was temperature dependent and required the presence of divalent cations such as calcium. The agglutination of human O erythrocytes by Vibrio cholerae was observed also, and the hemagglutination test appeared to detect the same mechanism that was involved in the adhesion of vibrios to brush borders. When the bacteria were grown in broth they were adhesive and hemagglutinating, but vibrios grown on agar plates or suspended in buffer for 15 min at 37 C lacked these abilities, even though they retained undiminished motility. These two model systems differed, however, in that strontium promoted only adhesion to brush borders. The significance of this difference remains to be determined. Vibrios were observed to penetrate intestinal mucus gel and occasionally to become entrapped in it. However, there was no evidence that vibrios attached to mucus gel.

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.