Hydrogen Peroxide in the Lung Parenchyma Stimulates Vagally Mediated Phrenic Activity

Abstract

To elucidate the mechanism of hyperpnea and tachypnea, which are the common findings in cardiopulmonary patients. Recently, it was found that activating pulmonary afferents by directly injecting hypertonic saline solution into the lung periphery causes a vagally mediated neural hyperpnea and tachypnea, ie, the excitatory lung reflex. Since reactive oxygen species are released during a variety of pulmonary diseases, we examined whether hydrogen peroxide (H(2)O(2)), a common mediator in cardiopulmonary diseases, can initiate the same excitatory lung reflex. We recorded phrenic efferent activity in anesthetized, open chest, artificially ventilated rabbits as an index of respiratory drive and examined the respiratory responses to injections of H(2)O(2) (10 micromol in 0.1 mL). The responses were compared with those to hypertonic saline solution (8.1%, 0.1 mL). H(2)O(2) and hypertonic saline solution increased both the rate (mean [+/- SEM], 43 +/- 8% and 61 +/- 10%, respectively; n = 30; p = 0.001) and the amplitude of phrenic bursts (12 +/- 2% and 20 +/- 4%, respectively; n = 30; p = 0.033). These responses were abolished by bilateral vagotomy. H(2)O(2) can initiate the excitatory lung reflex. Therefore, mediator(s) released in pulmonary diseases could be one of the mechanisms causing hyperpnea and tachypnea.