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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 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.

Animals↗

[Effect of the volatile anesthetics halothane, enflurane and isoflurane on liver circulation in the human].

In 40 patients with normal liver function total hepatic blood flow (HBF) was determined by the indocyanine-green clearance method simultaneously with haemodynamic parameters, including cardiac output by means of the noninvasive thoracic electrical bioimpedance method. Furthermore, the influence of halothane, enflurane or isoflurane on HBF and the interaction with haemodynamic parameters was studied. HBF and the cardiocirculatory parameters were determined under normal conditions (waking state) and the 40 patients were then divided into 4 groups (each n = 10). After standardised induction of anaesthesia (0.3 mg/kg etomidate and 2 micrograms/kg fentanyl) and tracheal intubation (1.5 mg/kg suxamethonium chloride) an inhalation anaesthesia in O2/air under control of normal end tidal carbon dioxide concentration was performed by intermittent positive pressure ventilation. Anaesthesia was maintained in the 4 groups either with 1 MAC halothane, 1 MAC enflurane, 1 MAC isoflurane or 1.3 MAC isoflurane. The measurements were repeated at a steady of the desired end expiratory concentration of the respective volatile anaesthetic. All three anaesthetics produced a significant and comparable decrease of cardiac output and arterial blood pressure. Differences between halothane, enflurane and isoflurane in respect of haemodynamic parameters were only minimal. Contrariwise, marked differences could be seen in the effects of the anaesthetics on HBF. In the presence of halothane and enflurane HBF dropped to 58% and 56% resp. of the control value, whereas during isoflurane anaesthesia HBF remained unchanged. Furthermore, only during halothane anaesthesia a significant correlation between arterial blood pressure and HBF could be observed indicating a loss of autoregulation of the hepatic blood flow.

Adolescent↗