The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis

Marc O. Maybauer, Dirk M. Maybauer, Perenlei Enkhbaatar, Régent Laporte, Halina Winiewska, Lillian D. Traber, Chiidean Lin, Juanjuan Fan, Hal K. Hawkins, Robert A. Cox, Kazimierz Winiewski, Claudio D. Schteingart, Donald W. Landry, Pierre J M Rivière, Daniel L. Traber

Research output: Contribution to journalArticle

33 Citations (Scopus)

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. DESIGN:: Prospective, randomized, controlled laboratory experiment. SETTING:: University animal research facility. SUBJECTS:: Forty-five chronically instrumented sheep. INTERVENTIONS:: 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. MEASUREMENTS AND MAIN 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.

Original languageEnglish (US)
JournalCritical Care Medicine
Volume42
Issue number7
DOIs
StatePublished - 2014

Fingerprint

Vasopressin Receptors
Blood Vessels
Sheep
Sepsis
Arginine Vasopressin
Deamino Arginine Vasopressin
Pseudomonas aeruginosa
Arterial Pressure
Phe(2)-Ile(3)-Hgn(4)-Orn(iPr)(8)-vasopressin
Tracheostomy
Hematocrit
Resuscitation
Smoke
Vascular Resistance
Ventilation
Pneumonia
Therapeutics
Hormones

Keywords

  • capillary leak syndrome
  • sepsis
  • vasoconstrictor agents
  • vasopressins

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis. / Maybauer, Marc O.; Maybauer, Dirk M.; Enkhbaatar, Perenlei; Laporte, Régent; Winiewska, Halina; Traber, Lillian D.; Lin, Chiidean; Fan, Juanjuan; Hawkins, Hal K.; Cox, Robert A.; Winiewski, Kazimierz; Schteingart, Claudio D.; Landry, Donald W.; Rivière, Pierre J M; Traber, Daniel L.

In: Critical Care Medicine, Vol. 42, No. 7, 2014.

Research output: Contribution to journalArticle

Maybauer, MO, Maybauer, DM, Enkhbaatar, P, Laporte, R, Winiewska, H, Traber, LD, Lin, C, Fan, J, Hawkins, HK, Cox, RA, Winiewski, K, Schteingart, CD, Landry, DW, Rivière, PJM & Traber, DL 2014, 'The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis', Critical Care Medicine, vol. 42, no. 7. https://doi.org/10.1097/CCM.0000000000000300
Maybauer, Marc O. ; Maybauer, Dirk M. ; Enkhbaatar, Perenlei ; Laporte, Régent ; Winiewska, Halina ; Traber, Lillian D. ; Lin, Chiidean ; Fan, Juanjuan ; Hawkins, Hal K. ; Cox, Robert A. ; Winiewski, Kazimierz ; Schteingart, Claudio D. ; Landry, Donald W. ; Rivière, Pierre J M ; Traber, Daniel L. / The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis. In: Critical Care Medicine. 2014 ; Vol. 42, No. 7.
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T1 - The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis

AU - Maybauer, Marc O.

AU - Maybauer, Dirk M.

AU - Enkhbaatar, Perenlei

AU - Laporte, Régent

AU - Winiewska, Halina

AU - Traber, Lillian D.

AU - Lin, Chiidean

AU - Fan, Juanjuan

AU - Hawkins, Hal K.

AU - Cox, Robert A.

AU - Winiewski, Kazimierz

AU - Schteingart, Claudio D.

AU - Landry, Donald W.

AU - Rivière, Pierre J M

AU - Traber, Daniel L.

PY - 2014

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N2 - 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. DESIGN:: Prospective, randomized, controlled laboratory experiment. SETTING:: University animal research facility. SUBJECTS:: Forty-five chronically instrumented sheep. INTERVENTIONS:: 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. MEASUREMENTS AND MAIN 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.

AB - 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. DESIGN:: Prospective, randomized, controlled laboratory experiment. SETTING:: University animal research facility. SUBJECTS:: Forty-five chronically instrumented sheep. INTERVENTIONS:: 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. MEASUREMENTS AND MAIN 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.

KW - capillary leak syndrome

KW - sepsis

KW - vasoconstrictor agents

KW - vasopressins

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