Aprotinin and the systemic inflammatory response after cardiopulmonary bypass.
Cardiopulmonary bypass is associated with a systemic inflammatory response, a spectrum of pathophysiologic changes ranging from mild organ dysfunction to multisystem organ failure. Complications include coagulation disorders (bleeding diathesis, hyperfibrinolysis) from platelet defects and plasmin activation, as well as pulmonary dysfunction from neutrophil sequestration and degranulation. Diverse injuries are a consequence of multiple inflammatory mediators (complement, kinins, kallikrein, cytokines). Both plasmin and kallikrein amplify the inflammatory response by activating components of the contact activation system. The full-Hammersmith (high dose) of aprotinin, a serine protease inhibitor approved for reducing blood loss and transfusion requirements in cardiopulmonary bypass, inhibits kallikrein and plasmin, resulting in suppression of multiple systems involved in the inflammatory response. Specifically, inhibition of factor XII, bradykinin, C5a, neutrophil integrin expression, elastase activity, and airway nitric oxide production are observed. Clinical correlates include reduced capillary leak, preserved systemic vascular resistance and blood pressure, and improved myocardial recovery following ischemia. Overall, evidence indicates that aprotinin attenuates the systemic inflammatory response associated with cardiopulmonary bypass.
Department of Clinical Development, Alexion Pharmaceuticals, Inc, New Haven, Connecticut 06511, USA. mojcikc@alxn.com
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Levy
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000097:blood; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology*
D018836:Inflammation Mediators; D007611:Aprotinin