EFFECT OF PLATELET-ACTIVATING-FACTOR ANTAGONIST (CV-3988) ON 6-KETO-PGF(1)ALPHA AND THROMBOXANE B-2 IN DOGS WITH EXPERIMENTAL ENDOTOXIN-INDUCED SHOCK

The effect of CV-3988, a platelet activating factor antagonist, in the treatment of endotoxic shock was evaluated from the changes in plasma 6-keto-PGF(1) alpha and thromboxane B-2 concentrations. The animals c onsisted of 10 beagle dogs anesthetized with pentobarbital sodium and divided into a treatment group (n=5) and a control group (n=5). Endoto xic shock was experimentally induced in both groups by intravenous adm inistration of endotoxin (lipopolysaccharide, 3 mg/kg). The treatment group was intravenously given 10 mg/kg of CV-3988 for 10 min from imme diately after endotoxin. Mean aortic pressure, cardiac output and urin e volume were remarkably decreased after the administration of endotox in to both groups. These parameters were higher after the administrati on of CV-3988, in the treatment group than in the control group. Furth ermore, the increase in plasma 6-keto-PGF(1) alpha and thromboxane B-2 concentrations was significantly inhibited. These results suggest the effectiveness of CV-3988 in the treatment of endotoxic shock.