Acute exposure to aerosolized carfentanil (CRF) can lead to severe ventilatory depression associated with hypoxia and hypercapnia. It is well-known that ventilatory responses to hypoxia and hypercapnia are essential for maintaining a normal breathing; however, the impact of CRF exposure on these chemoreflexes remains unclear. The goal of this study was to verify the effect of CRF exposure on the integrative phrenic nerve activity (∫PN) responses to hypoxia and hypercapnia. After the left phrenic nerve isolation and femoral arterial cannulation, two groups of anesthetized and spontaneously breathing rats were exposed to aerosolized vehicle (Ctrl) and CRF (1.7 mg/m3) for 15 min respectively in a plethysmography and then removed from the chamber followed by vagotomy, paralysis and artificial ventilation. The baseline cardiorespiratory activities the peak and frequency of ∫PN (∫PN pk and f) and minute phrenic activity (MPN, ∫PNpk X f), heart rate (HR), arterial blood pressure (ABP) and SpO 2 /PETCO 2 and their responses to hypoxia (10% O 2 for 1 min) and hypercapnia (10% CO 2 for 3 min) were recorded. In the Ctrl, both hypoxia (lowering SpO 2 to 70%) and hypercapnia (increasing PETCO 2 to 70 Torr) augmented ∫PNpk, f and MPN and hypoxia but not hypercapnia significantly decreased ABP. CRF exposure alone resulted in substantial depression of MPN and ∫PNpk as well as hypertension. After CRF exposure, the responses of MPN and ∫PNpk to hypoxia and hypercapnia were markedly diminished compared to the Ctrl and the hypoxia-induced hypertension was reversed. Neither CRF exposure nor hypoxia challenge significantly affected HR. Our results indicate that CRF exposure suppresses central inspiratory drive as well as its response to hypoxia and hypercapnia, leading to the CRF inhalation-induced ventilatory depression. Supported by HL163512 and DA059063. This abstract was presented at the American Physiology Summit 2026 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.
ZHUANG et al. (Fri,) studied this question.