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.

Inflammatory Role of AMP-Activated Protein Kinase Signaling in an Experimental Model of Toxic Smoke Inhalation Injury*

“…Furthermore, it is also known that the pathogenetic mechanisms underlying inhalation lung injury are multiple (2,3). For example, inhaled toxic smoke may stimulate lung C fibers through the action of ROS (49) and promote the release of calcitonin generelated peptide, an inflammatory mediator that is important to the pathogenesis of inhalation lung injury (50). Particularly, O 2…”

Beneficial pulmonary effects of a metalloporphyrinic peroxynitrite decomposition catalyst in burn and smoke inhalation injury

“…OD) was placed into an efferent lymphatic vessel from the caudal mediastinal lymph node for the measurement of lung lymph flow (Q L). The systemic lymph contribution was removed by ligation of the tail of the caudal mediastinal lymph node and cauterization of the the systemic diaphragmatic lymph vessels (5,17,28). After a recovery period of 5-7 days, a baseline measurement was performed in spontaneously breathing sheep.…”

Molecular biological effects of selective neuronal nitric oxide synthase inhibition in ovine lung injury

“…Another important feature of this model is that the hemodynamic stability allows for invasive cardiovascular monitoring for many hours. Evidently, the ovine animal model has substantially contributed to the investigation of combined burn and smoke inhalation injury (19,24,26,27,36). For this study, we have chosen a 24-h period, since our aim was to identify the molecular mechanisms resulting within 1 day after combined burn and smoke inhalation injury.…”