AMINOETHYL‐ISOTHIOUREA, A SELECTIVE INHIBITOR OF INDUCIBLE NITRIC OXIDE SYNTHASE ACTIVITY, IMPROVES LIVER CIRCULATION AND OXYGEN METABOLISM IN A PORCINE MODEL OF ENDOTOXEMIA

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 μg/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 (QHA) from 266 ± 53 to 127 ± 19 mL/min, and in portal venous flow (QPV) 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 QHA 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.