title: Hepatocellular dysfunction persists during early sepsis despite increased volume of crystalloid resuscitation.
abstract: Although hepatocellular dysfunction occurs early in sepsis despite fluid resuscitation, it is unknown if an increased volume of resuscitation protects hepatocellular function. To study this, rats were subjected to sepsis by cecal ligation and puncture (CLP). These and sham-treated rats then received either 3 or 6 mL/100 g BW normal saline subcutaneously. Studies were performed at 5 hours (i.e., early sepsis) or 20 hours (late sepsis) after CLP. Hepatic blood flow was determined by radioactive microspheres, 3H-galactose clearance technique, and laser Doppler flowmetry in both groups. Active hepatocellular function (i.e., Vmax and Km) was assessed by an in vivo indocyanine green clearance technique. The results indicate that: (1) hepatic blood flow increased markedly in early sepsis; (2) Vmax and Km decreased significantly at 5 hours and 20 hours after CLP; and (3) the increased volume of fluid resuscitation did not improve the depressed active hepatocellular function 5 hours following CLP. Cardiac output and hepatic microcirculation, however, were significantly increased in early sepsis. These results confirm the notion that the depression in hepatocellular function in early sepsis is not the result of any reduction of hepatic perfusion. The dissociation of increased hepatic blood flow from depressed hepatocellular function remains despite the larger volume of resuscitation. The hepatocellular dysfunction that occurs even in early sepsis cannot be corrected simply by increasing the volume of crystalloid resuscitation.
authors.affiliation: Shock and Trauma Research Laboratories, Michigan State University, East Lansing 48824-1315.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: Z F
authors.initials: ZF
authors.lastname: Ba
authors.forename: A
authors.initials: A
authors.lastname: Ayala
authors.forename: I H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D002302:Cardiac Output; D005690:Galactose / Q000493:pharmacokinetics; D007208:Indocyanine Green; D007263:Infusions, Parenteral; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D008863:Microspheres; D051381:Rats; D011919:Rats, Inbred Strains; D018805:Sepsis / Q000378:metabolism* / Q000628:therapy; D012965:Sodium Chloride / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D012965:Sodium Chloride; D007208:Indocyanine Green; D005690:Galactose