The use of TP10, soluble complement receptor 1, in cardiopulmonary bypass.
Cardiopulmonary bypass (CPB) for cardiac surgery or lung transplantation initiates a systemic inflammatory response characterized by increased vascular permeability, generalized edema, abnormal lung function and oxygenation and impaired ventricular function. This post-CPB syndrome significantly contributes to postoperative morbidity and mortality. Activation of complement during CPB is a key component that initiates and augments this process. TP10, soluble complement receptor 1, is a novel complement inhibitor that is a potent inhibitor of C3 and C5 convertases, blocking activation of the complement cascade at the nexus of all three complement pathways. Recent controlled trials in humans have demonstrated that TP10 effectively inhibits complement activation during CPB. In high-risk adult patients, TP10 decreases the incidence of mortality and myocardial infarction in males but not in females following cardiac surgery. TP10 is also well tolerated and protects vascular function in infants undergoing CPB. In addition, TP10 leads to early extubation in adult lung transplant recipients. TP10 is currently positioned for clinical development in a male-only indication of cardiac surgery on CPB.
Li
Jennifer S
JS
Duke University Medical Center, Division of Pediatric Cardiology, Department of Pediatrics, Duke Clinical Research Institute, Box 3090, Durham, NC 27710, USA. jennifer.li@duke.edu
Jaggers
James
J
Anderson
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PA
D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control*; D051056:Complement Inactivating Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D016040:Lung Transplantation; D011951:Receptors, Complement / Q000627:therapeutic use*; D016896:Treatment Outcome
D051056:Complement Inactivating Agents; D011951:Receptors, Complement; C082885:soluble complement inhibitor 1