thromboxane-b2 and nafamostat

Topics: Animals; Benzamidines; Dogs; Guanidines; Male; Nitrites; Pancreas; Pancreas Transplantation; Protease Inhibitors; Reperfusion Injury; Thromboxane B2; Transplantation, Autologous

The aim of this study was to investigate the effect of Nafamostat mesilate (FUT-175) on some blood platelet properties during the first hours of acute experimental pancreatitis (AEP) in dogs. A significant decrease in platelet count, hyperaggregability of platelets by ADP and PAF as well as an increased level of TXB2, were found in the early stage of AEP. No changes in platelet aggregation induced with AA were demonstrated. FUT-175 prevented a decrease in platelet number and inhibited platelet aggregation induced with ADP, PAF and AA when it was given immediately after induction of AEP. No evident changes in TXB2 levels in dogs treated with FUT-175 were found. Our results indicate that the positive effect of FUT-175 in AEP in part depends on its antiaggregatory action.

Topics: Acute Disease; Animals; Benzamidines; Blood Platelets; Dogs; Guanidines; Male; Pancreatitis; Platelet Aggregation Inhibitors; Platelet Count; Protease Inhibitors; Thromboxane B2

Rapid protamine reversal of heparin anticoagulation in awake sheep caused, after 1 min, a approximately 15-fold increase of arterial plasma thromboxane B2 (TxB2) levels, a 4-fold rise of pulmonary vascular resistance (PVR), a 2-fold rise of pulmonary arterial pressure, and after 3 min, a 2-fold rise of ovine arterial plasma complement C3a levels (P less than 0.05). Infusion of nafamstat mesilate (FUT-175), a protease and complement pathway inhibitor, before protamine reduced these increases by approximately 60-90% (P less than 0.05). FUT-175 did not modify heparin + protamine-induced leukopenia, suggesting that FUT-175 incompletely blocked C5a production. We also learned that infusing protamine first and heparin 5 min later did not increase either plasma C3a or TxB2 levels or PVR while the activated clotting time increased only minimally. Thus, in awake sheep, the sequence of heparin and protamine infusion influences complement activation and pulmonary vasoconstriction. FUT-175 pretreatment reduces thromboxane release and pulmonary vasoconstriction probably by limiting complement activation.

Topics: Animals; Benzamidines; Blood Pressure; Complement C3a; Complement Inactivator Proteins; Drug Interactions; Guanidines; Hemodynamics; Heparin; Hypertension, Pulmonary; Lung; Protamines; Protease Inhibitors; Pulmonary Artery; Sheep; Thromboxane B2; Vascular Resistance