title: Terlipressin dose response in healthy and endotoxemic sheep: impact on cardiopulmonary performance and global oxygen transport.
abstract: OBJECTIVE
  To determine whether a goal-directed terlipressin infusion increases mean arterial pressure without causing a pulmonary vasopressive effect and whether this response impacts on key parameters of oxygen transport in healthy and endotoxemic sheep.
  
  
  METHODS
  Prospective controlled trial in a university research laboratory.
  
  
  METHODS
  Six conscious adult ewes instrumented for chronic study received terlipressin as titrated infusion started with 10 microg x kg(-1) x h(-1) and increased by 5 microg x kg(-1) x h(-1) every 15 min, either until mean arterial pressure was increased by 15 mmHg from baseline, or a maximum of 40 microg x kg(-1) x h(-1) was given. Following 24 h of recovery sepsis was induced and maintained in the same ewes by a continuous infusion of endotoxin ( Salmonella typhosa, 10 ng x kg(-1) min(-1)). After 16 h of endotoxemia the sheep were again treated with terlipressin.
  
  
  RESULTS
  Systemic oxygen delivery and consumption were calculated before and after the titration period; hemodynamic parameters were measured every 15 min. The increase in mean arterial pressure was greater during endotoxemia than in healthy controls. In both states terlipressin administration decreased cardiac index and diminished oxygen delivery and consumption. While mean pulmonary arterial pressure remained constant, terlipressin increased the pulmonary vascular resistance index in endotoxemic sheep.
  
  
  CONCLUSIONS
  During ovine endotoxemia titrated terlipressin reversed hypotension but impaired the pulmonary circulation. The observed decrease in oxygen delivery may carry the risk of tissue hypoxia especially in sepsis, where oxygen demand is typically increased.
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany. mwestpha@uni-muenster.de
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
authors.forename: Henning
authors.initials: H
authors.lastname: Stubbe
authors.forename: Andreas Wilhelm
authors.initials: AW
authors.lastname: Sielenkämper
authors.forename: Reka
authors.initials: R
authors.lastname: Borgulya
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: Christian
authors.initials: C
authors.lastname: Ball
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Bone
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000150:complications*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008236:Lypressin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects; D015657:Respiratory Transport / Q000187:drug effects*; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D000077585:Terlipressin; D014435:Typhoid Fever / Q000150:complications*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin