title: Aminoethyl-isothiourea, a selective inhibitor of inducible nitric oxide synthase activity, improves liver circulation and oxygen metabolism in a porcine model of endotoxemia.
abstract: The role of nitric oxide (NO) in hepatic oxygen transport is unclear. We investigated the effects of aminoethyl-isothiourea (AE-ITU), a selective inhibitor of iNOS activity, on liver blood flow and oxygen consumption (VO2H) in the pig. Endotoxin (lipopolysaccharide, LPS) was given intraportally (1.7 microg/kg/h), followed by AE-ITU (10 mg/kg) after 3 h (n = 7), LPS controls (n = 8) received LPS for 6 h. AE-ITU controls (n = 6) received saline/AE-ITU. LPS (treatment group) caused significant reductions at 3 h in cardiac output (CO) from 4.4 +/- .4 to 2.7 +/- .3 L/min, in hepatic artery flow (Q(HA)) from 266 +/- 53 to 127 +/- 19 mL/min, and in portal venous flow (Q(PV)) from 630 +/- 50 to 323 +/- 33 mL/min. Hepatic oxygen delivery (DO2H) was reduced from 93 +/- 11 to 38 +/- 5 mL/min (p < .05), while hepatic oxygen extraction ratio (ERO2H) increased, and VO2H was maintained. Similar changes were observed in LPS controls. AE-ITU caused no changes in saline controls. After injection of AE-ITU during LPS infusion, CO was unchanged, while Q(HA) increased gradually from 127 +/- 20 to 268 +/- 40 mL/min over 3 h (p < .05) and DO2H from 38 +/- 5 to 60 +/- 5 mL/in (p < .05). ERO2H increased from .54 +/- .04 to .69 +/- .03 in 30 min, while VO2H increased from 23 +/- 4 to 35 +/- 3 mL/in in 3 h (p < .05). Thus, AE-ITU restored hepatic arterial blood flow and increased hepatic oxygen consumption in pigs with endotoxemia.
authors.affiliation: Institute for Surgical Research, Rikshospitalet, The National Hospital, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Saetre
authors.forename: Y
authors.initials: Y
authors.lastname: Gundersen
authors.forename: C
authors.initials: C
authors.lastname: Thiemermann
authors.forename: P
authors.initials: P
authors.lastname: Lilleaasen
authors.forename: A O
authors.initials: AO
authors.lastname: Aasen
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008102:Liver Circulation / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen / Q000378:metabolism*; D013552:Swine; D013890:Thiourea; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D000338:beta-Aminoethyl Isothiourea; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D013890:Thiourea; D010100:Oxygen