Reduction of myocardial infarct size by neutrophil depletion: Effect of duration of occlusion

Abstract

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.

NS-398, a Cyclooxygenase-2-Specific Inhibitor, Delays Skeletal Muscle Healing by Decreasing Regeneration and Promoting Fibrosis

“…Some researchers have hypothesized that neutrophils exacerbate muscle injuries by releasing reactive oxygen intermediates, including peroxides, hypochlorite, and superoxide. [47][48][49][50][51] During muscle healing, different populations of macrophages perform different roles, including phagocytosis and the release of growth factors. 52,53 CD-11b (also called Mac-1) is a neutrophil surface antigen.…”

Double-Blind, Randomized Trial of an Anti-CD18 Antibody in Conjunction With Recombinant Tissue Plasminogen Activator for Acute Myocardial Infarction

“…18 By contrast, in dogs with neutrophil depletion, myocardial necrosis was reduced with ischemia of either 90 or 240 minutes. 5 Sharar et al 3 found, using a rabbit ear preparation and 6 hours of occlusion, that administration of anti-CD18 therapy immediately on reperfusion was as effective as that initiated 1 hour but not 4 hours later. No effect was observed when the antibody was administered after 12 hours.…”

Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link

“…Interestingly, PMNs were shown to infiltrate eroded or ruptured plaques obtained from patients with acute coronary syndromes [119,120], and to participate in the pathogenesis of lethal myocardial reperfusion [121]. Notably, depleting PMNs resulted in reduced myocardial infarct size and a protected myocardium [122,123].…”