Selected Contribution: Intermittent hypoxia induces phrenic long-term facilitation in carotid-denervated rats

Abstract
Episodic hypoxia elicits a long-lasting augmentation of phrenic inspiratory activity known as long-term facilitation (LTF). We investigated the respective contributions of carotid chemoafferent neuron activation and hypoxia to the expression of LTF in urethane-anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats. One hour after three 5-min isocapnic hypoxic episodes [arterial Po 2(PaO2 ) = 40 ± 5 Torr], integrated phrenic burst amplitude was greater than baseline in both carotid-denervated ( n = 8) and sham-operated ( n = 7) rats ( P < 0.05), indicating LTF. LTF was reduced in carotid-denervated rats relative to sham ( P < 0.05). In this and previous studies, rats were ventilated with hyperoxic gas mixtures (inspired oxygen fraction = 0.5) under baseline conditions. To determine whether episodic hyperoxia induces LTF, phrenic activity was recorded under normoxic (PaO2 = 90–100 Torr) conditions before and after three 5-min episodes of isocapnic hypoxia (PaO2 = 40 ± 5 Torr; n = 6) or hyperoxia (PaO2 > 470 Torr; n= 6). Phrenic burst amplitude was greater than baseline 1 h after episodic hypoxia ( P < 0.05), but episodic hyperoxia had no detectable effect. These data suggest that hypoxia per se initiates LTF independently from carotid chemoafferent neuron activation, perhaps through direct central nervous system effects.