Clinical evaluation of a new synthetic protease inhibitor in open heart surgery. Effect on plasma serotonin and histamine release and blood conservation.
To achieve more physiologically successful cardiopulmonary bypass (CPB), the effects of a new synthetic protease inhibitor, nafamostat mesilate (FUT), were examined in open heart surgery. Thirty adult patients were divided into two groups. In Group F (GpF; n = 15), 2 mg/kg/hr of FUT was administered continuously during CPB and 0.2 mg/kg/hr before and after CPB. FUT was not given to Group C patients (GpC; n = 15), who acted as controls. Serotonin and histamine levels in plasma, platelet counts, platelet adhesive function levels, and alpha 2 plasmin inhibitor-plasmin complexes (PIC) were serially measured. The serotonin level in GpF was significantly lower at 5 min of CPB than in GpC. Histamine levels in GpC decreased remarkably after starting CPB, then later recovered; by contrast, they did not decrease in GpF during CPB. At 1 hr after CPB, platelet counts were higher (p < 0.01) in GpF (54 +/- 8%) than in GpC (41 +/- 10%), and platelet adhesion was lower (p < 0.01) in GpF (7 +/- 7%) than in GpC (34 +/- 13%). The PIC was significantly less in GpF than in GpC throughout the surgery. Blood loss in GpF was significantly reduced compared with that in GpC. In conclusion, FUT attenuated chemical mediator reactions, such as plasma serotonin and histamine, and also reduced blood loss by preserving platelets and inhibiting fibrinolysis during CPB.
D000328:Adult; D000368:Aged; D001550:Benzamidines; D016063:Blood Loss, Surgical / Q000517:prevention & control; D002315:Cardiopulmonary Bypass; D006146:Guanidines / Q000627:therapeutic use*; D006488:Hemostasis, Surgical; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012701:Serotonin / Q000097:blood
D001550:Benzamidines; D006146:Guanidines; D011480:Protease Inhibitors; D012701:Serotonin; C032855:nafamostat