title: Low-dose terlipressin during long-term hyperdynamic porcine endotoxemia: effects on hepatosplanchnic perfusion, oxygen exchange, and metabolism.
abstract: OBJECTIVE
  To investigate whether the vasopressin analog terlipressin might induce hepatosplanchnic ischemia during long-term, hyperdynamic, volume-resuscitated porcine endotoxemia.
  
  
  METHODS
  Prospective, randomized, controlled experimental study with repeated measures.
  
  
  METHODS
  Investigational animal laboratory.
  
  
  METHODS
  Eighteen pigs were divided into two groups receiving either endotoxin alone (control group, n = 10) or endotoxin and terlipressin (n = 8).
  
  
  METHODS
  Pigs were anesthetized, mechanically ventilated, and instrumented and received a continuous intravenous infusion of Escherichia coli endotoxin. Animals were resuscitated with hydroxyethyl starch targeted to maintain mean arterial pressure >60 mm Hg. Twelve hours after the start of the endotoxin infusion, terlipressin (5-15 microg.kg.hr titrated to maintain mean arterial pressure at preendotoxin levels) or its vehicle was administered for 12 hrs.
  
  
  RESULTS
  Terlipressin increased mean arterial pressure and systemic vascular resistances, which was affiliated with a decrease in cardiac output and global oxygen consumption. Terlipressin restored the hepatic artery buffer response, which led to an increase in hepatic artery flow, ultimately resulting in well-maintained liver oxygen delivery, oxygen uptake, and all other variables of regional metabolism and organ function. Terlipressin markedly attenuated the hepatosplanchnic venous acidosis but was associated with pronounced hyperlactatemia.
  
  
  CONCLUSIONS
  During long-term hyperdynamic porcine endotoxemia, the well-known vasoconstrictor properties of terlipressin blunted the progressive decrease in mean arterial pressure without any detrimental effect on hepatosplanchnic perfusion, oxygen exchange, and metabolism. The marked terlipressin-induced hyperlactatemia did not originate from the hepatosplanchnic organs but from extrasplanchnic tissues, possibly muscle and skin.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Ulm, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Balázs
authors.initials: B
authors.lastname: Hauser
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Iványi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ehrmann
authors.forename: Jochen
authors.initials: J
authors.lastname: Kick
authors.forename: Maura
authors.initials: M
authors.lastname: Albicini
authors.forename: Josef
authors.initials: J
authors.lastname: Vogt
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wachter
authors.forename: Uwe Bernd
authors.initials: UB
authors.lastname: Brückner
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bracht
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D019446:Endotoxemia / Q000378:metabolism / Q000503:physiopathology*; D004731:Endotoxins; D004926:Escherichia coli; D005260:Female; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides; D008102:Liver Circulation / Q000187:drug effects*; D008236:Lypressin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D008297:Male; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D019289:Pyruvic Acid / Q000097:blood; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D000077585:Terlipressin; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D019344:Lactic Acid; D008236:Lypressin; C044101:endotoxin, Escherichia coli; D000077585:Terlipressin; D019289:Pyruvic Acid; D005947:Glucose; D010100:Oxygen