P-selectin inhibition prevents early neutrophil activation but provides only modest protection against myocardial injury in dogs with ischemia and forty-eight hours reperfusion
| Autor: | Pascal J. Goldschmidt-Clermont, Cynthia O. Siu, Masazumi Arai, Takeshi Kondo, Yoshihiro Masui, Lewis C. Becker, Anthony DiPaula |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
P-selectin medicine.medical_treatment Ischemia Collateral Circulation Myocardial Reperfusion Injury CD18 Cross Reactions 030204 cardiovascular system & hematology Neutrophil Activation Random Allocation 03 medical and health sciences Dogs 0302 clinical medicine Internal medicine medicine Carnivora Animals Saline 030304 developmental biology 0303 health sciences biology Vascular disease business.industry Fissipedia Antibodies Monoclonal biology.organism_classification medicine.disease Collateral circulation Coronary Vessels Disease Models Animal P-Selectin Evaluation Studies as Topic Regional Blood Flow Immunology Cardiology Female Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of the American College of Cardiology. 34:280-288 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/s0735-1097(99)00160-6 |
| Popis: | OBJECTIVES This study was designed to determine whether antibody neutralization of the adhesion protein P-selectin would prevent neutrophil activation and reduce myocardial reperfusion injury. BACKGROUND Although inhibition of P-selectin markedly reduces short-term myocardial injury after ischemia and reperfusion, it is unknown whether it can provide meaningful long-term protection and preserve left ventricular function. METHODS Closed-chest dogs underwent 90 min left anterior descending coronary artery occlusion and 48 h reperfusion, and were randomized to 1) a treatment group (n = 11) receiving 1 mg/kg of the blocking anti-P-selectin antibody PB1.3, or 2) a control group receiving 1 mg/kg PNB1.6 (nonblocking antibody against P-selectin, n = 7) or an equivalent volume of saline (n = 2) 10 min before reperfusion. Infarct size was assessed postmortem by triphenyl tetrazolium chloride staining. Contrast left ventriculography was used to measure left ventricular function. Activation of circulating polymorphonuclear neutrophils (PMNs) was assessed by an increase in surface CD18 expression. RESULTS Neutrophil activation was observed at 30 min after reperfusion in the control group, but was abolished in the treatment group. Infarct size was reduced about 25% in the treatment group after controlling for variations in ischemic blood flow (p = 0.003, by analysis of covariance). However, this protective effect was not associated with preservation of blood flow to the ischemic-reperfused myocardium, nor with any improvement in global or regional left ventricular function. CONCLUSIONS The anti-P-selectin antibody PB1.3 prevented early PMN activation, but had only a modest long-term infarct-limiting effect over 48 h reperfusion. Adhesion molecules other than P-selectin may mediate delayed PMN activation and accumulation in reperfused myocardium. |
| Databáze: | OpenAIRE |
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