Abstract
The prevention of postoperative intravascular coagulation is an important problem in surgery, but the definitive procedure has not been established. In 1974 the reduction of the deposition of fibrin in the lungs by Trasylol after intravenous injection of thromboplastin was reported by Diffang et al. That Gabexate mesilate (FOY), a synthetic protease inhibitor, weakly reduced the activity of thrombin is also known.
FOY could affect the prothrombin time and also the activated partial thromboplastin time at final concentration of 2.4×10-5M, or more (Fig. 1). Therefore the deposition of fibrin in the lungs after injection of thromboplastin and thrombin was determined by the method of Saldeen (1969), in which 125I-human fibrinogen was used. The rats were given 0.01% potassium iodine in their drinking water. One μCi radioactive human fibrinogen per 100g body weight was injected into a tail vein 48 hours before the experiment. Radioactivity in the rat's lung after bleeding was determined in the experiment. The rats were given 0.5mg of FOY one minute before thromboplastin or thrombin injection, and 5 minutes after the injection. The rats were killed 10 and 40 minutes after the beginning of the injection of thromboplastin, thrombin or saline. FOY injection was found to reduce the deposition of fibrin in the lungs significantly 10 minutes after the injection of 5mg of thromboplastin per 100g body weight by determining radioactivity in the lungs (Fig. 2). Meanwhile, FOY injection was not found to reduce the deposition of fibrin significantly 10 minutes after the injection of 12.5 units per 100g body weight (Fig. 3). However, the deposition of fibrin was somewhat reduced by FOY injection on the average as compared with the control. The alteration of plasma fibrinogen and serum FDP was determined 10 or 40 minutes after the injection of thromboplastin or thrombin. But there was no significant difference between two groups.
By microscope-search ten minutes after the injection of thromboplastin, moderate amounts of fibrin were observed in the lungs of the rat given thromboplastin alone, as well as in those injected with FOY and thromboplastin. There was no significant difference in the amounts of fibrin.
Finally, the present study suggests that a high concentration of FOY may be usefull as the inhibitor against the intravascular coagulation. That the activity of FOY was eliminated early after the injection, was due to a high activity of esterase in rats. From this property of FOY, it seems to be more appropriate to give this drug to patients after surgery rather than to ones with DIC.
