Biomaterial Database

A selective inhibitor for inducible nitric oxide synthase improves hypotension and lactic acidosis in canine endotoxic shock. 2001

C Mitaka, and Y Hirata, and K Yokoyama, and K Makita, and T Imai

Department of Critical Care Medicine, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. c.mitaka.icu@med.tmd.ac.jp

OBJECTIVE To investigate whether ONO-1714, a putative selective inhibitor for inducible nitric oxide synthase, modulates systemic hemodynamics, arterial blood gases, lactate concentrations, gastric mucosal perfusion, and renal and hepatic functions in endotoxic shock. METHODS Prospective, randomized, controlled animal study. METHODS Laboratory at a university hospital. METHODS Eighteen male beagle dogs (12-19 kg) under pentobarbital anesthesia. METHODS Dogs were mechanically ventilated and monitored with a pulmonary arterial catheter and a gastric tonometer. They were divided in three groups: a) lipopolysaccharide (LPS) plus vehicle group (n = 6), which received LPS (250 ng/kg/min for 2 hrs) and saline 1 hr later; b) LPS plus ONO (0.05) group (n = 6), which received ONO-1714 (0.05 mg/kg) 1 hr after the start of LPS; c) LPS plus ONO (0.1) group (n = 6), which received ONO-1714 (0.1 mg/kg) 1 hr after the start of LPS. RESULTS Hemodynamics, blood gas parameters, gastric intramural pH, urine output, and serum levels of lactate, transaminases, bilirubin, and creatinine were measured during a 6-hr observation period. LPS induced hypotension, lactic acidosis, gastric mucosal acidosis, and renal and hepatic dysfunction. ONO-1714 reversed the LPS-induced hypotension and lactic acidosis without deteriorating cardiac output, oxygen delivery, or gastric mucosal acidosis. CONCLUSIONS These findings suggest that ONO-1714 is a useful agent to reverse hypotension and lactic acidosis in a canine endotoxic shock model.

UI	MeSH Term	Description	Entries
D007022	Hypotension	Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.	Blood Pressure, Low,Hypotension, Vascular,Low Blood Pressure,Vascular Hypotension
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D008297	Male		Males
D001784	Blood Gas Analysis	Measurement of oxygen and carbon dioxide in the blood.	Analysis, Blood Gas,Analyses, Blood Gas,Blood Gas Analyses,Gas Analyses, Blood,Gas Analysis, Blood
D003404	Creatinine		Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006439	Hemodynamics	The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.	Hemodynamic
D006574	Heterocyclic Compounds, 2-Ring	A class of heterocyclic compounds that include a two-ring fused structure. Both aromatic and non-aromatic ring structures are included in this category.	Fused Heterocyclic Compounds, Two-Ring,Two Ring Heterocyclic Compounds,2-Ring Heterocyclic Compounds,Fused Heterocyclic Compounds, Two Ring,Heterocyclic Compounds, 2 Ring
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations