title: Role of calcitonin gene-related peptide (CGRP) in ovine burn and smoke inhalation injury.
abstract: Concomitant smoke inhalation trauma in burn patients is a serious medical problem. Previous investigations in our sheep model revealed that these injuries lead to significant airway hyperemia, enhanced pulmonary fluid extravasation, and severely impaired pulmonary function. However, the pathophysiological mechanisms are still not fully understood. The lung is innervated by sensory nerves containing peptides such as substance P and calcitonin gene-related peptide. Noxious stimuli in the airways can induce a neurogenic inflammatory response, which has previously been implicated in several airway diseases. Calcitonin gene-related peptide is known to be a potent vasodilator. We hypothesized that calcitonin gene-related peptide is also a mediator of the pulmonary reaction to toxic smoke and planned experiments to evaluate its role in this model. We tested the effects of pretreatment with a specific antagonist of the major receptor for calcitonin gene-related peptide (BIBN4096BS; 32 microg/kg, followed by continuous infusion of 6.4 microg.kg(-1).h(-1)) until the animal was killed 48 h after injury in an established ovine model of burn (40% total body surface, third degree) and smoke inhalation (48 breaths, <40 degrees C) injury. In treated animals (n = 7), the injury-related increases in tracheal blood flow and lung lymph flow were significantly attenuated compared with untreated controls (n = 5). Furthermore, the treatment significantly attenuated abnormalities in respiratory gas exchange. The data suggest that calcitonin gene-related peptide contributes to early airway hyperemia, transvascular fluid flux, and respiratory malfunction following ovine burn and smoke inhalation injury. Future studies will be needed to clarify the potential therapeutic benefit for patients with this injury.
authors.affiliation: Investigational Intensive Care Unit, Dept. of Anesthesiology, The Univ. of Texas Medical Branch, 301 Univ. Blvd., Galveston, TX 77550, USA. lanm@gmx.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Lange
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cox
authors.forename: Sam
authors.initials: S
authors.lastname: Jacob
authors.forename: Babu P
authors.initials: BP
authors.lastname: Mathew
authors.forename: Atsumori
authors.initials: A
authors.lastname: Hamahata
authors.forename: Lillian D
authors.initials: LD
authors.lastname: Traber
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Hal K
authors.initials: HK
authors.lastname: Hawkins
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008196:Lymph / Q000502:physiology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D014132:Trachea / Q000098:blood supply; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D011799:Quinazolines; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant