Acute effects of intravenous irritants on breathing rate, heart rate and blood gases in anesthetized mice

The airways are densely innervated by irritant-sensitive nociceptive vagal afferent nerves whose activation evokes acute modulation of respiration and heart rate. Previous studies in larger mammals have shown that irritants such as capsaicin (pungent ingredient in chili), when given intravenously, evoke a triple response of rapid shallow breathing (RSB), apnea, and bradycardia. Here, we studied this cardiopulmonary reflex in anesthetized mice, measuring heart rate with surface ECG, breathing rate with diaphragmatic EMG (dEMG), end-tidal CO2 (ETCO2) with a capnograph, and oxygen saturation (SpO2) with pulse oximetry in response to 20ml i.v. injection (via jugular vein) of vehicle or capsaicin (3 mg/ml) or allyl isothiocyanate (AITC, 3-10 mg/ml), the pungent ingredient in wasabi. Vehicle evoked little or no change in parameters. Whereas the irritants, capsaicin and AITC, within 2-3s of injection evoked dramatic bradycardia and bradypnea (accompanied by a decrease in dEMG amplitude). ETCO2 decreased during periods of apnea, but individual breath ETCO2 values during these responses were not lower than pre-injection values. In some cases, RSB was observed after the bradypneic period, which was accompanied by a slow decrease in ETCO2 to ~80% pre-injection values. These data suggest that irritant-evoked cardiopulmonary reflexes in mice predominantly evoke bradypnea/apnea rather than RSB. Furthermore these data suggest that irritant-evoked changes in blood gases do not appear to be the initial cause of the cardiopulmonary reflex, suggesting the evoked bradycardia and bradypnea are due to a direct reflex effect of the activation of vagal nociceptive afferents innervating the airways. RO1HL152219 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.