Pharmacology and Biological Efficacy of a Recombinant, Humanized, Single-Chain Antibody C5 Complement Inhibitor in Patients Undergoing Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass
| العنوان: | Pharmacology and Biological Efficacy of a Recombinant, Humanized, Single-Chain Antibody C5 Complement Inhibitor in Patients Undergoing Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass |
|---|---|
| المؤلفون: | Gary S. Kopf, Philip Kraker, Roberta Hines, Louis A. Matis, Richard K. Shaw, Gregory L. Stahl, Bernadette Alford, Sary F. Aranki, Lan Li, Ruth O'Hara, Charles D. Collard, Michael L. Dewar, Henry M. Rinder, Scott A. Rollins, Brian G. Smith, Jane C. K. Fitch, John A. Elefteriades, Stanton K. Shernan, Christine S. Rinder |
| المصدر: | Circulation. 100:2499-2506 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 1999. |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | medicine.medical_specialty, Blood Loss, Surgical, Coronary Disease, Myocardial Reperfusion Injury, Inflammation, Complement Membrane Attack Complex, Pharmacology, Antibodies, Monoclonal, Humanized, law.invention, Proinflammatory cytokine, Complement inhibitor, Postoperative Complications, law, Physiology (medical), Pexelizumab, Cardiopulmonary bypass, medicine, Humans, Prospective Studies, Coronary Artery Bypass, Complement Activation, Creatine Kinase, Complement component 5, Psychological Tests, Cardiopulmonary Bypass, biology, business.industry, Antibodies, Monoclonal, Complement C5, Middle Aged, Complement system, Surgery, Isoenzymes, Integrin alpha M, biology.protein, medicine.symptom, Cognition Disorders, Cardiology and Cardiovascular Medicine, business, Single-Chain Antibodies, medicine.drug |
| الوصف: | Background —Cardiopulmonary bypass (CPB) induces a systemic inflammatory response that causes substantial clinical morbidity. Activation of complement during CPB contributes significantly to this inflammatory process. We examined the capability of a novel therapeutic complement inhibitor to prevent pathological complement activation and tissue injury in patients undergoing CPB. Methods and Results —A humanized, recombinant, single-chain antibody specific for human C5, h5G1.1-scFv, was intravenously administered in 1 of 4 doses ranging from 0.2 to 2.0 mg/kg before CPB. h5G1.1-scFv was found to be safe and well tolerated. Pharmacokinetic analysis revealed a sustained half-life from 7.0 to 14.5 hours. Pharmacodynamic analysis demonstrated significant dose-dependent inhibition of complement hemolytic activity for up to 14 hours at 2 mg/kg. The generation of proinflammatory complement byproducts (sC5b-9) was effectively inhibited in a dose-dependent fashion. Leukocyte activation, as measured by surface expression of CD11b, was reduced ( P P =0.05) in patients who received 2 mg/kg. Sequential Mini-Mental State Examinations (MMSE) demonstrated an 80% reduction in new cognitive deficits ( P P Conclusions —A single-chain antibody specific for human C5 is a safe and effective inhibitor of pathological complement activation in patients undergoing CPB. In addition to significantly reducing sC5b-9 formation and leukocyte CD11b expression, C5 inhibition significantly attenuates postoperative myocardial injury, cognitive deficits, and blood loss. These data suggest that C5 inhibition may represent a novel therapeutic strategy for preventing complement-mediated inflammation and tissue injury. |
| تدمد: | 1524-4539 0009-7322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afd859c72b26df8380d1356aba652dc5 https://doi.org/10.1161/01.cir.100.25.2499 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....afd859c72b26df8380d1356aba652dc5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
|---|