Effects of the bradykinin B2 receptor antagonist Icatibant on microvascular permeability after thermal injury in sheep

Collette C. Jonkam, Perenlei Enkhbaatar, Yoshimitsu Nakano, Thomas Boehm, Jianpu Wang, Juerg Nussberger, Aimalohi Esechie, Lillian D. Traber, David Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Peptide kinins are potent vasoactive agents in the microcirculation that might be released after burn injury. The present study was designed to test the hypothesis that Icatibant (JE 049), a potent, selective peptidomimetic bradykinin-B2 receptor antagonist, would reduce the cardiovascular pathology occurring in sheep exposed to 40% total body surface area (TBSA), third-degree burn. Female sheep were surgically prepared for chronic study. After 5 to 7 days' recovery from the operative procedure, they were randomized to five groups: sham (n = 6, noninjured, nontreated), medicated sham (n = 4, noninjured, treated with 20 μg kg h Icatibant), control (n = 7, 40% TBSA third-degree burn, nontreated), Icatibant-4 (n = 6, 40% TBSA third-degree burn, treated with 4 μg kg h Icatibant [low dose]), Icatibant-20 (n = 8, 40% TBSA third-degree burn, treated with 20 μg kg h Icatibant [high dose]). Prefemoral lymph flow (milliliters per hour) remained constant in the sham and medicated sham groups but increased after injury: control (0 h, 3.9 ± 0.5; 24 h, 28 ± 4.2; 48 h, 33.0 ± 8.1). The increased fluid flux was associated with enhanced protein flux. Both low and high doses of Icatibant significantly reduced the microvascular fluid flux: Icatibant-4 (0 h, 5.3 ± 0.6; 24 h, 17.5 ± 3.5; 48 h, 20.3 ± 3.4); Icatibant-20 (0 h, 5.3 ± 1.1; 24 h, 15.2 ± 2; 48 h, 17.6 ± 4.1). Total prefemoral protein leak was reduced in all treatment groups. The low dose of Icatibant significantly reduced prefemoral lymph flow without adversely affecting the hemodynamic changes observed after burn injury in sheep, suggesting that the bradykinin antagonist would reduce edema formation and improve fluid management of thermally injured patients.

Original languageEnglish (US)
Pages (from-to)704-709
Number of pages6
JournalShock
Volume28
Issue number6
DOIs
StatePublished - Dec 2007

Fingerprint

Capillary Permeability
Sheep
Hot Temperature
Wounds and Injuries
Body Surface Area
Lymph
Bradykinin B2 Receptor Antagonists
icatibant
Peptidomimetics
Kinins
Operative Surgical Procedures
Microcirculation
Edema
Proteins
Hemodynamics
Pathology
Peptides

Keywords

  • Burn injury
  • Edema
  • Fluid resuscitation
  • Lymph flow
  • Protein leak

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

Effects of the bradykinin B2 receptor antagonist Icatibant on microvascular permeability after thermal injury in sheep. / Jonkam, Collette C.; Enkhbaatar, Perenlei; Nakano, Yoshimitsu; Boehm, Thomas; Wang, Jianpu; Nussberger, Juerg; Esechie, Aimalohi; Traber, Lillian D.; Herndon, David; Traber, Daniel L.

In: Shock, Vol. 28, No. 6, 12.2007, p. 704-709.

Research output: Contribution to journalArticle

Jonkam, CC, Enkhbaatar, P, Nakano, Y, Boehm, T, Wang, J, Nussberger, J, Esechie, A, Traber, LD, Herndon, D & Traber, DL 2007, 'Effects of the bradykinin B2 receptor antagonist Icatibant on microvascular permeability after thermal injury in sheep', Shock, vol. 28, no. 6, pp. 704-709. https://doi.org/10.1097/shk.0b013e3180536124
Jonkam, Collette C. ; Enkhbaatar, Perenlei ; Nakano, Yoshimitsu ; Boehm, Thomas ; Wang, Jianpu ; Nussberger, Juerg ; Esechie, Aimalohi ; Traber, Lillian D. ; Herndon, David ; Traber, Daniel L. / Effects of the bradykinin B2 receptor antagonist Icatibant on microvascular permeability after thermal injury in sheep. In: Shock. 2007 ; Vol. 28, No. 6. pp. 704-709.
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abstract = "Peptide kinins are potent vasoactive agents in the microcirculation that might be released after burn injury. The present study was designed to test the hypothesis that Icatibant (JE 049), a potent, selective peptidomimetic bradykinin-B2 receptor antagonist, would reduce the cardiovascular pathology occurring in sheep exposed to 40{\%} total body surface area (TBSA), third-degree burn. Female sheep were surgically prepared for chronic study. After 5 to 7 days' recovery from the operative procedure, they were randomized to five groups: sham (n = 6, noninjured, nontreated), medicated sham (n = 4, noninjured, treated with 20 μg kg h Icatibant), control (n = 7, 40{\%} TBSA third-degree burn, nontreated), Icatibant-4 (n = 6, 40{\%} TBSA third-degree burn, treated with 4 μg kg h Icatibant [low dose]), Icatibant-20 (n = 8, 40{\%} TBSA third-degree burn, treated with 20 μg kg h Icatibant [high dose]). Prefemoral lymph flow (milliliters per hour) remained constant in the sham and medicated sham groups but increased after injury: control (0 h, 3.9 ± 0.5; 24 h, 28 ± 4.2; 48 h, 33.0 ± 8.1). The increased fluid flux was associated with enhanced protein flux. Both low and high doses of Icatibant significantly reduced the microvascular fluid flux: Icatibant-4 (0 h, 5.3 ± 0.6; 24 h, 17.5 ± 3.5; 48 h, 20.3 ± 3.4); Icatibant-20 (0 h, 5.3 ± 1.1; 24 h, 15.2 ± 2; 48 h, 17.6 ± 4.1). Total prefemoral protein leak was reduced in all treatment groups. The low dose of Icatibant significantly reduced prefemoral lymph flow without adversely affecting the hemodynamic changes observed after burn injury in sheep, suggesting that the bradykinin antagonist would reduce edema formation and improve fluid management of thermally injured patients.",
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