Fentanyl depresses the Phrenic Nerve Response to Hypoxia and Hypercapnia

Intravenous (IV) perfusion of opioids inhibits hypoxic and hypercapnic ventilatory response in humans and animals. However, the impacts of IV bolus injection of fentanyl (FNT) on these chemoreflexes are unknown, which is the objective of this study. The integrative phrenic nerve activity (∫PN, as an index of respiratory motor output), heart rate (HR), arterial blood pressure (ABP) and pulse oxygen saturation (SpO 2 )/end-tidal CO 2 partial pressure (PETCO 2 ) along with their responses to hypoxia (10% O 2 for 1 min) and hypercapnia (10% CO 2 for 3 min) were recorded in anesthetized, vagotomized, paralyzed and ventilated rats before and 5 min after intravenous bolus (IVb) injection of vehicle (Ctrl) and FNT (30 µg/kg). Phrenic nerve activity included the peak and frequency of ∫PN (∫PNpk and f) and minute phrenic activity (MPN, ∫PNpk X f), equivalent to tidal volume, respiratory frequency and minute ventilation. Our data showed that hypoxia (decreasing SpO 2 to 70%) brought about an increase in MPN, f and ∫PNpk with little change in ABP and HR in the Ctrl. FNT alone caused an immediate sustained apnea followed by subsequent 65% reduction of MPN and ∫PNpk and hypertension without remarkable change in HR. Five min after FNT, MPN response to hypoxia was attenuated by 40% via lowering ∫PNpk response and FNT-induced hypertension was reversed by hypoxia without HR change. Hypercapnic exposure (increasing PETCO 2 to 70 Torr) enhanced MPN and ∫PNpk without remarkable change in ABP and HR in the Ctrl. Among these hypercapnic responses, MPN and ∫PNpk, but not f, responses were substantially diminished after FNT. Our results suggest that FNT markedly depresses central inspiratory drive and its response to hypoxia and hypercapnia. 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.