Protection of reperfused ischemic canine myocardium by CI-922, a new inhibitor of leukocyte activation.
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 CI-922, 23 +/- 4 (p less than 0.05 vs. control). There were no significant inter-group 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 microM), 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/10(6) cells (p less than 0.05). Thus, inhibition of neutrophil-mediated damage may explain the cardioprotective effect of CI-922.
Werns
S W
SW
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
Eller
B T
BT
Shea
M J
MJ
Simpson
P J
PJ
Dysko
R C
RC
Abrams
G D
GD
Lucchesi
B R
BR
D000818:Animals; D001393:Azoles / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D013481:Superoxides; D013777:Tetrazoles / Q000627:therapeutic use*
D001393:Azoles; D007211:Indoles; D013777:Tetrazoles; D013481:Superoxides; C045584:CI 922; D009195:Peroxidase