Role of calcitonin gene-related peptide (CGRP) in ovine burn and smoke inhalation injury

Matthias Lange, Perenlei Enkhbaatar, Daniel L. Traber, Robert A. Cox, Sam Jacob, Babu P. Mathew, Atsumori Hamahata, Lillian D. Traber, David Herndon, Hal K. Hawkins

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 μg/kg, followed by continuous infusion of 6.4 μg·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°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.

Original languageEnglish (US)
Pages (from-to)176-184
Number of pages9
JournalJournal of Applied Physiology
Volume107
Issue number1
DOIs
StatePublished - Jul 2009

Fingerprint

Smoke Inhalation Injury
Calcitonin Gene-Related Peptide
Sheep
Wounds and Injuries
Lung
Smoke
Hyperemia
Inhalation
Calcitonin Receptors
Poisons
Lymph
Substance P
Vasodilator Agents
Gases
Peptides
Therapeutics

Keywords

  • Airway blood flow
  • Bronchial circulation
  • Neurogenic inflammation
  • Neuropeptides
  • Pulmonary microcirculation
  • Sheep

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Role of calcitonin gene-related peptide (CGRP) in ovine burn and smoke inhalation injury. / Lange, Matthias; Enkhbaatar, Perenlei; Traber, Daniel L.; Cox, Robert A.; Jacob, Sam; Mathew, Babu P.; Hamahata, Atsumori; Traber, Lillian D.; Herndon, David; Hawkins, Hal K.

In: Journal of Applied Physiology, Vol. 107, No. 1, 07.2009, p. 176-184.

Research output: Contribution to journalArticle

Lange, M, Enkhbaatar, P, Traber, DL, Cox, RA, Jacob, S, Mathew, BP, Hamahata, A, Traber, LD, Herndon, D & Hawkins, HK 2009, 'Role of calcitonin gene-related peptide (CGRP) in ovine burn and smoke inhalation injury', Journal of Applied Physiology, vol. 107, no. 1, pp. 176-184. https://doi.org/10.1152/japplphysiol.00094.2009
Lange, Matthias ; Enkhbaatar, Perenlei ; Traber, Daniel L. ; Cox, Robert A. ; Jacob, Sam ; Mathew, Babu P. ; Hamahata, Atsumori ; Traber, Lillian D. ; Herndon, David ; Hawkins, Hal K. / Role of calcitonin gene-related peptide (CGRP) in ovine burn and smoke inhalation injury. In: Journal of Applied Physiology. 2009 ; Vol. 107, No. 1. pp. 176-184.
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