A lack of stimulatory effect of chlorine gas on vagal bronchopulmonary C-fibers

Because of the widespread use of chlorine (Cl 2 ) as a chemical agent in various industrial operations, it is extensively documented that numerous incidences resulting from accidental release of large quantities and high concentrations of Cl 2 from industrial facility have led to severe lung injuries and fatalities. Inhalation of Cl 2 at high concentration even for a short duration immediately evoked cough and reflex bronchoconstriction in healthy individuals, suggesting an involvement of stimulation of airway sensory nerves. Vagal bronchopulmonary C-fiber sensory nerves, the dominant type of afferents innervating the entire respiratory tract, play a pivotal role in eliciting the protective reflexes and defending the lung against inhaled chemical irritants, such as Cl 2 . However, whether inhaled Cl 2 gas activates these afferents is not yet known. This study was carried out to determine if inhalation of Cl 2 gas generated a stimulatory effect on vagal bronchopulmonary C-fiber afferents in anesthetized Sprague-Dawley rats; Cl 2 gas was delivered into the lung via a tracheal tube and respirator at high concentrations for a short duration. The afferent activity arising from C-fiber nerve endings located in the airways and lungs was measured using the "single-fiber" recording technique in open-chest, mechanically ventilated rats. The precise location of the C-fiber receptor in the lung structures was identified in each fiber. Our results showed: 1) inhalation of Cl 2 at a high concentration (400 ppm), which had been shown to induce acute lung injury in rats, for a relatively short duration (10-30 sec) to simulate accidental inhalation exposures in the industrial environment, did not cause a clear and consistent stimulatory effect on vagal bronchopulmonary C-fibers; 2) the average C-fiber activity at baseline (air) was 0.21± 0.06 impulses/sec (n=4) and the peak activity of the same C-fibers after inhalation of Cl 2 (400 ppm) was 0.22 ± 0.11 impulses/sec ( P> 0.05); 3) a weak and detectable stimulatory effect on these C-fibers was evoked only when the Cl 2 concentration was elevated to 1500-2000 ppm for a long duration of exposure (60 sec). In conclusion, these results clearly indicated that inhalation of Cl 2 at high concentrations for a short duration, simulating the occupational accidental exposures, failed to evoke a consistent and significant stimulatory effect of inhaled Cl 2 on bronchopulmonary C-fibers. A lack of pulmonary chemoreflex responses mediated through activation of these pulmonary C-fibers may, therefore, contribute in part to the extremely hazardous effects caused by the inhalation exposure to this potent toxic gas during industrial accident. Supported in part by research grants from the National Institutes of Health ES026529 and Merck MISP100107. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.