title: Severe hypoxemia in the absence of blood loss depresses hepatocellular function and up-regulates IL-6 and PGE2.
abstract: Although hepatocellular function is depressed early after trauma and hemorrhage (which are associated with low flow conditions and tissue hypoxemia), it remains unknown whether hypoxemia without blood loss, produces hepatocellular dysfunction and, if so, whether IL-6 and PGE2 are associated with this dysfunction. To study this, rats were placed in a plastic box which was flushed with a gas mixture containing 6.3% O2:93.7% N2 or room air for 60 min, followed by their return to room air. At 0 and 4 h after hypoxemia, hepatocellular function (i.e., maximum velocity of indocyanine green clearance (Vmax) and the efficiency of the transport (Km)) was measured using an in vivo hemoreflectometer. Cardiac output was assessed by dye dilution technique. Tissue microvascular blood flow was determined by laser Doppler flowmetry. Plasma IL-6 and PGE2 were measured by bioassay and radioimmunoassay, respectively. The results indicate that hypoxemia produced a depression in hepatocellular function (i.e., decreased Vmax by 44-50% and Km by 55-68%) despite stable cardiac output and hepatic microcirculation at 0 and 4 h after hypoxemia. Moreover, hypoxemia resulted in a significant increase in plasma IL-6 (by 372%-389%) as well as PGE2 (by 38% at 0 h post-hypoxemia). Thus, hypoxemia observed after trauma and hemorrhagic shock appears to be responsible for producing hepatocellular dysfunction possibly through the up-regulation of IL-6 and PGE2. In view of this, long-lasting hypoxemia in trauma victims should be avoided, perhaps by early intubation and ventilation so that the potential additional proinflammatory cytokine and PGE2 release can be prevented.
authors.affiliation: Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: Z F
authors.initials: ZF
authors.lastname: Ba
authors.forename: I H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002302:Cardiac Output; D015232:Dinoprostone / Q000096:biosynthesis*; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008099:Liver / Q000503:physiopathology*; D051381:Rats; D012771:Shock, Hemorrhagic / Q000150:complications; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D015232:Dinoprostone