Studies on Production of Antithrombin III with Special Reference to Endotoxin-Induced DIC in Dogs

Abstract

The production of antithrombin III (AT III) was studied using Se-75-selenomethionine as a tracer in dogs with disseminated intravascular coagulation (DIC) experimentally induced by endotoxin infusion. Using canine AT III purified by heparin-Sepharose affinity chromatography, antiserum against canine AT III was raised in rabbit. To study the production of plasma AT III, Se-75-selenomethionine was injected into the dog and thereafter the radioactivity incorporated into plasma AT III immunoprecipitated by anti-AT III rabbit serum was serially measured. In normal control dogs, peak radioactivity incorporated into AT III fraction was 970 +/- 55 (mean +/- SE) cpm/mg of AT III. It was 1196 +/- 51.5 cpm/mg, 2748 +/- 826 cpm/mg and 1057 +/- 74 cpm/mg when Se-75-selenomethionine was injected 6 h, 24 h and 48 h after a single infusion with one mg of endotoxin/kg body weight of dogs, and was 1.2 times, 2.8 times and 1.1 times more than normal control dogs, respectively. Plasma AT III levels decreased to a minimum of 26.7 +/- 4.9 mg/dl within 6 h after endotoxin infusion and returned to normal levels by 2 to 3 days after the infusion. Since the catabolic rate of AT III was evidently accelerated, judging from the more rapid decay of the AT III radioactivity, it is suggested that the production of AT III is markedly increased in dogs with DIC induced by endotoxin infusion even during a period of low plasma level.