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 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.
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Authors | S W Werns, B T Eller, M J Shea, P J Simpson, R C Dysko, G D Abrams, B R Lucchesi |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 12
Issue 5
Pg. 608-14
( 1988)
ISSN: 0160-2446 [Print] United States |
PMID | 2468062
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Azoles
- Indoles
- Tetrazoles
- Superoxides
- CI 922
- Peroxidase
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Topics |
- Animals
- Azoles
(therapeutic use)
- Coronary Circulation
(drug effects)
- Dogs
- Electrocardiography
- Hemodynamics
(drug effects)
- Indoles
(therapeutic use)
- Male
- Myocardial Reperfusion Injury
(prevention & control)
- Myocardium
(enzymology)
- Neutrophils
(metabolism)
- Peroxidase
(metabolism)
- Superoxides
- Tetrazoles
(therapeutic use)
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