title: Effects of the bradykinin B2 receptor antagonist icatibant on microvascular permeability after thermal injury in sheep.
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 microg kg h Icatibant), control (n = 7, 40% TBSA third-degree burn, nontreated), Icatibant-4 (n = 6, 40% TBSA third-degree burn, treated with 4 microg kg h Icatibant [low dose]), Icatibant-20 (n = 8, 40% TBSA third-degree burn, treated with 20 microg 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.
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch and Shriners Hospital for Children, 610 Texas Avenue, Galveston, TX 77551, USA.
authors.forename: Collette C
authors.initials: CC
authors.lastname: Jonkam
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Nakano
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
authors.forename: Jianpu
authors.initials: J
authors.lastname: Wang
authors.forename: Juerg
authors.initials: J
authors.lastname: Nussberger
authors.forename: Aimalohi
authors.initials: A
authors.lastname: Esechie
authors.forename: Lillian D
authors.initials: LD
authors.lastname: Traber
authors.forename: David
authors.initials: D
authors.lastname: Herndon
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D002056:Burns / Q000097:blood / Q000150:complications* / Q000628:therapy; D002199:Capillary Permeability / Q000187:drug effects*; D004487:Edema / Q000209:etiology / Q000517:prevention & control; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D012756:Sheep
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; C065679:icatibant; D001920:Bradykinin