REVIPARIN-SODIUM PREVENTS COMPLEMENT-MEDIATED MYOCARDIAL INJURY IN THE ISOLATED RABBIT HEART

The cytoprotective action of reviparin-sodium (LU-47311; Clivarin), a low-molecular-weight heparin, was examined in an ex vivo model of comp lement-mediated myocardial injury. The effective concentration of revi parin was determined by using an in vitro rabbit erythrocyte-lysis ass ay using 4% normal human plasma. Reviparin (0.01-2.73 mg/ml) reduced e rythrocyte lysis in a concentration-dependent manner. Subsequently, 0. 91 mg/ml of reviparin was evaluated in an ex vivo rabbit isolated-hear t model of human complement-mediated injury. Hearts perfused in the pr esence of 0.91 mg/ml of reviparin (n = 10) demonstrated significant pr eservation of ventricular function compared with vehicle-treated heart s (n = 10), as evidenced by coronary artery perfusion pressure, left-v entricular developed pressure, and left ventricular end-diastolic pres sure. A reduction in myocyte creatine kinase release was observed in r eviparin-treated hearts compared with controls. Myocardial injury in v ehicle-treated hearts was associated with an increased assembly of the membrane-attack complex, as determined by immunohistochemical localiz ation of C5b-9 neoantigen. Reviparin decreased fluid-phase Bb formatio n detected in the lymphatic drainage of plasma-perfused hearts. The re sults of this study demonstrate that reviparin inhibits complement-med iated myocardial injury as assessed in an ex vivo experimental model o f complement activation.