[Experimental study on heparin-free cardiopulmonary bypass using nafamostat mesilate (FUT-175) and heparin-coated...

We investigated whether the combination of a new synthetic protease inhibitor, nafamostat mesilate (FUT-175), and heparin-coated cardiopulmonary bypass (CPB) circuit can achieve heparin-free CPB in rabbits. Nine rabbits underwent 2 hours of CPB with heparin-coated circuits. In 4 rabbits (FUT-Group), FUT was administered before (2 mg/kg in bolus) and during (5 mg/kg/hr continuously) CPB. In 5 rabbits (Heparin-Group), heparin was given before (4 mg/kg) and at 1 hour (2 mg/kg) of CPB. Activated clotting time, activated partial thromboplastin time and fibrin degradation products showed no significant differences between the two groups during CPB. However, prothrombin time was significantly (p < 0.05) shorter in FUT-Group than in Heparin-Group. Platelet counts in FUT-Group was significantly lower than Heparin-Group. Massive clots were observed in all of the venous reservoirs of FUT-Group after CPB, whereas there were no major clots in Heparin-Group. The occlusion rate of hollow fibers of the oxygenators was significantly higher in FUT-Group (55 +/- 25%, mean +/- SD) than in Heparin-Group (14 +/- 12%). We concluded that heparin-free CPB with FUT and heparin-coated circuit is difficult in rabbits because activation of the extrinsic coagulation cascade cannot be sufficiently suppressed by FUT.