Experimental Results Using Nafamostat Mesilate as Anticoagulant During Extracorporeal Lung Assist for 24 Hours in Dogs

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Abstract
We report on the experimental application of nafamostat mesilate (NM, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate, FUT), a new anticoagulant, to extracorporeal lung assist (ECLA) with an artificial membrane lung. Venovenous ECLA, from the jugular vein to the femoral vein, was performed with a hollow-fiber membrane lung at a blood flow rate of approximate 82 ml kg-1 min-1 for 24 h in 7 dogs under anesthesia and hypoventilation. Heparin (10 U ml-1 in a priming lactated Ringer solution of 140 ml, and 200 U kg-1) was administered before blood access cannulation. After start of ECLA, however, no heparin was used, and nafamostat mesilate was continuously infused into the drainage line of the bypass circuit to control activated coagulation time (ACT) at about 150 to 200 s. To maintain the prolonged ACT, 8.0 +/- 1.7 mg kg-1 h-1 of NM was required. Arterial blood pressure and pulse rate decreased significantly. Though fibrin monomer test revealed hypercoagulability after 6 h of ECLA, platelet counts did not significantly decrease. Total blood loss remained less than 40 g. The artificial membrane lung sustained a good gas exchange and low flow resistance throughout ECLA. Macroscopic examination revealed small spotty thrombi in the artificial lung but no major pathologic changes of the visceral organs in the all dogs at autopsy. High-dose NM administration could control blood coagulation and decrease blood loss during ECLA for 24 h without deterioration of the artificial lung and systemic complication other than mild hypotension and bradycardia.