Nafamostat prevents hypothermia and improves survival time after administration of lipopolysaccharide in a mouse surgical model

Abstract

Lipopolysaccharide (LPS) is an endotoxin known to induce disseminated intravascular coagulation and multiple organ failure followed by septic shock in animals. Nafamostat is a synthetic protease inhibitor with anticoagulant effects. This study investigated the effect of systemic administration of nafamostat on thermogenic homeostasis and survival time in a mouse surgical model. Male C57Bl/6 mice were anesthetized with sevoflurane and implanted with intraabdominal telemetry transmitters. Following the surgery, three groups of animals were administered Escherichia coli LPS (0127: B8) subcutaneously at doses of 0.3, 1.0, or 3.0 mg kg(-1), and one group received saline without LPS. Three other groups received 3 mg.kg(-1) LPS with 1, 3, or 10 mg kg(-1) of nafamostat. In another group 10 mg kg(-1)1 of nafamostat only was administered. The times to the onset of hypothermia (body temperature < 30 degrees C) and death were determined. L LPS significantly shortened the duration of both normothermia and survival, and nafamostat prolonged the normothermic periods that were reduced b 3 mg.kg(-1) LPS. Survival time was significantly correlated with the duration of normothermia (n = 48; r (2) = 0.779; P < 0.000001). The results demonstrated the effect of systemic administration of nafamostat against LPS-induced hypothermia. Nafamostat prevented hypothermia, and the consequent normal thermoregulation may have prolonged the survival period.