Protection of Reperfused Ischemic Canine Myocardium by CI-922, a New Inhibitor of Leukocyte Activation

Publisher Website
Google Scholar
Abstract
There is increasing evidence that activated neutrophils cause myocardial injury during reperfusion of ischemic myocardium. This study was performed to assess the effect of CI-922, an inhibitor of neutrophil activation, in a canine preparation of myocardial infarction. Dogs received 15-min infusions of CI-922 1 mg/kg or 5% dextrose beginning 30 min before occlusion of the left circumflex coronary artery. After occlusion for 90 min and reperfusion for 6 h, infarct size was determined by ex vivo perfusion of the left circumflex coronary artery with triphenyltetrazolium chloride. The percentage of the area at risk infarcted was: control, 42 ± 5; and Cl-922. 23 ± 4 (p < 0.05 vs. control). There were no significant intergroup differences in heart rate or mean arterial pressure, and CI-922 did not enhance collateral blood flow to the ischemic bed. After incubation with CI-922 (100 μM), production of superoxide anions by canine neutrophils activated by opsonized zymosam decreased from 3.5 ± 0.2 to 2.0 ± 0.4 nmol/10 min/106 cells (p < 0.05). Thus, inhibition of neutrophil-mediated damage may explain the cardioprotective effect of CI-922.