title: The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis*.
abstract: OBJECTIVE
  To determine if the selective vasopressin type 1a receptor agonist selepressin (FE 202158) is as effective as the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist vasopressor hormone arginine vasopressin when used as a titrated first-line vasopressor therapy in an ovine model of Pseudomonas aeruginosa pneumonia-induced severe sepsis.
  
  
  METHODS
  Prospective, randomized, controlled laboratory experiment.
  
  
  METHODS
  University animal research facility.
  
  
  METHODS
  Forty-five chronically instrumented sheep.
  
  
  METHODS
  Sheep were anesthetized, insufflated with cooled cotton smoke via tracheostomy, and P. aeruginosa were instilled into their airways. They were then placed on assisted ventilation, awakened, and resuscitated with lactated Ringer's solution titrated to maintain hematocrit ± 3% from baseline levels. If, despite fluid management, mean arterial pressure fell by more than 10 mm Hg from baseline level, an additional continuous IV infusion of arginine vasopressin or selepressin was titrated to raise and maintain mean arterial pressure within no less than 10 mm Hg from baseline level. Effects of combination treatment of selepressin with the selective vasopressin V2 receptor agonist desmopressin were similarly investigated.
  
  
  RESULTS
  In septic sheep, MAP fell by ~30 mm Hg, systemic vascular resistance index decreased by ~50%, and ~7 L of fluid were retained over 24 hours; this fluid accumulation was partially reduced by arginine vasopressin and almost completely blocked by selepressin; and combined infusion of selepressin and desmopressin increased fluid accumulation to levels similar to arginine vasopressin treatment.
  
  
  CONCLUSIONS
  Resuscitation with the selective vasopressin type 1a receptor agonist selepressin blocked vascular leak more effectively than the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist arginine vasopressin because of its lack of agonist activity at the vasopressin V2 receptor.
authors.affiliation: Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America.|Department of Anaesthesia and Intensive Care, Philipps University of Marburg, Marburg, Germany.
authors.forename: Marc O
authors.initials: MO
authors.lastname: Maybauer
authors.affiliation: Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America.|Department of Anaesthesia and Intensive Care, Philipps University of Marburg, Marburg, Germany.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Maybauer
authors.affiliation: Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
authors.affiliation: Ferring Research Institute, Inc., San Diego, California, United States of America.
authors.forename: Régent
authors.initials: R
authors.lastname: Laporte
authors.affiliation: Ferring Research Institute, Inc., San Diego, California, United States of America.
authors.forename: Halina
authors.initials: H
authors.lastname: Wiśniewska
authors.affiliation: Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Lillian D
authors.initials: LD
authors.lastname: Traber
authors.affiliation: Department of Mathematics and Statistics, San Diego State University, San Diego, California, United States of America.
authors.forename: ChiiDean
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Mathematics and Statistics, San Diego State University, San Diego, California, United States of America.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Hal K
authors.initials: HK
authors.lastname: Hawkins
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cox
authors.affiliation: Ferring Research Institute, Inc., San Diego, California, United States of America.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Wiśniewski
authors.affiliation: Ferring Research Institute, Inc., San Diego, California, United States of America.
authors.forename: Claudio D
authors.initials: CD
authors.lastname: Schteingart
authors.affiliation: Department of Medicine, Columbia University, New York City, New York, United States of America.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Landry
authors.affiliation: Ferring Research Institute, Inc., San Diego, California, United States of America.
authors.forename: Pierre J-M
authors.initials: PJ
authors.lastname: Rivière
authors.affiliation: Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006439:Hemodynamics; D018410:Pneumonia, Bacterial / Q000150:complications; D011550:Pseudomonas aeruginosa; D011897:Random Allocation; D017483:Receptors, Vasopressin / Q000819:agonists*; D015656:Respiratory Mechanics; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology; D012756:Sheep; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014667:Vasopressins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; C559490:vasopressin, Phe(2)-Ile(3)-Hgn(4)-Orn(iPr)(8)-; D014667:Vasopressins; D001127:Arginine Vasopressin