Inhibition of neutrophil adhesion during cardiopulmonary bypass
| Autor: | Jenny M. Bator, William E. Curtis, Duke E. Cameron, J.Mark Redmond, Kenton J. Zehr, William A. Baumgartner, A. Marc Gillinov, Bruce A. Reitz, Ahvie Herskowitz, Ian C. Wilson, Ronald M. Burch |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Neutrophils Swine CD18 Neutropenia Pharmacology law.invention Pulmonary function testing Leukocyte Count Antigens CD Leucine law Cell Adhesion medicine Cardiopulmonary bypass Animals Coronary Artery Bypass Lung biology business.industry Anti-Inflammatory Agents Non-Steroidal Respiratory disease medicine.disease Oxygen medicine.anatomical_structure CD18 Antigens Myeloperoxidase biology.protein Vascular resistance Vascular Resistance Surgery Cardiology and Cardiovascular Medicine business |
| Zdroj: | The Annals of Thoracic Surgery. 57:126-133 |
| ISSN: | 0003-4975 |
| DOI: | 10.1016/0003-4975(94)90380-8 |
| Popis: | Blood contact with synthetic surfaces during cardiopulmonary bypass (CPB) causes a diffuse inflammatory reaction that includes neutrophil activation. The purpose of this study was to determine if inhibition of neutrophil adhesion with a new antiinflammatory agent NPC 15669 (N-(9H-(2,7-dimethylfluorenyl-9-methoxy)-carbonyl)-L-leucine) could reduce pulmonary injury in a porcine model of CPB. NPC 15669 blocks adherence of activated neutrophils by inhibiting upregulation of the Mac-1 (CD11b/CD18) adhesion molecule. Sixteen piglets underwent 2 hours of hypothermic CPB followed by 2 hours of observation; 8 received NPC 15669 (10 mg/kg intravenous bolus followed by 6 mg.kg-1.h-1 intravenous infusion) and 8 received equal volumes of vehicle. After 90 minutes of CPB, expression of neutrophil adhesion molecule subunit CD18 increased 118% in control piglets but only 36% in piglets treated with NPC 15669 (p < 0.01). Although neutropenia developed in all animals during CPB, lung tissue myeloperoxidase content was significantly lower in treated than in control animals 2 hours after CPB (94.9 +/- 10.4 versus 46.9 +/- 5.5 mumol.10 mg-1.min-1; p < 0.002). Free radical-mediated lipid peroxidation (quantitated by spectrophotometric assay of plasma conjugated dienes) was significantly reduced by treatment with NPC 15669 during and after CPB. Pulmonary function was better in NPC 15669-treated animals: 2 hours after CPB, pulmonary vascular resistance increased 477% in control piglets but only 140% in piglets receiving NPC 15669 (p < 0.03); arterial oxygen tension was significantly greater in piglets receiving NPC 15669 (428 +/- 33 mm Hg) than in controls (141 +/- 46; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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