FORMATION OF Cl -Cl INHIBITOR AND KALLIKREIN-Cl INHIBITOR COMPLEXES DURING CARDIOPULMONARY BYPASS

Abstract

Cardiopulmonary bypass prolongs bleeding time and increases postoperative blood loss. Contact of blood with synthetic surfaces during extracorporeal circulation leads to major qualitative and quantitative alterations in both platelets and neutrophils. Activation of platelets results in thrombocytopenia, decreased sensitivity of platelets to aggregating agents, decreased alpha2-adrenergic and fibrinogen receptors, secretion of thromboxane B2, and depletion of alpha-granule protein contents. Neutrophils,under similar conditions, have also been shown to release their specific granule protein, lactoferrin, and their azurophilic granule enzyme, elastase.We now investigate whether the classical complement, contact, or fibrinolytic pathways have been activated as potential sources of neutrophil agonists. Employing enzyme-linked immunosorbent “sandwich” assays specific for Cl -Cl inhibitor and kalli-krein-Cl inhibitor complexes respectively, we found that plasma levels of both of these formed complexes increased 2fold after clinical cardiopulmonary bypass was completed and reverted to baseline within 24 hours post-operatively. Since these complexes are cleared iji vivo, we investigated their plasma levels during jLn vitro simulated extracorporeal circulation. Over a period of 2 hours, Cl -Cl inhibitor complexes rose from a baseline of 2 + InM to 21 + 2 nM and kalli-krein-Cl inhibitor complexes rose from 2+1 nM to 25 + 5 nM. However, there was no evidence of either in vivo or vitro plasmin-alpha plasmin inhibitor complex formation. These results indicate that activation of the classical pathway of complement and the contact system in plasma may be associated with neutrophil activation seen during clinical cardiopulmonary bypass.