title: 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.
authors.affiliation: Intensive Care Unit of University Hospital, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu city, Japan.
authors.forename: Yushi U
authors.initials: YU
authors.lastname: Adachi
authors.forename: Yukako
authors.initials: Y
authors.lastname: Obata
authors.forename: Katsumi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Katoh
authors.forename: Taiga
authors.initials: T
authors.lastname: Itagaki
authors.forename: Matsuyuki
authors.initials: M
authors.lastname: Doi
authors.forename: Shigehito
authors.initials: S
authors.lastname: Sato
mesh_terms: D000704:Analysis of Variance; D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001550:Benzamidines; D001831:Body Temperature / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007035:Hypothermia / Q000139:chemically induced / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000494:pharmacology*; D000077149:Sevoflurane; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D013534:Survival
chemical_list: D018685:Anesthetics, Inhalation; D001550:Benzamidines; D006146:Guanidines; D008070:Lipopolysaccharides; D008738:Methyl Ethers; D011480:Protease Inhibitors; D000077149:Sevoflurane; C032855:nafamostat