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) (Pa(O(2))) = 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 (Pa(O(2)) = 90-100 Torr) conditions before and after three 5-min episodes of isocapnic hypoxia (Pa(O(2)) = 40 +/- 5 Torr; n = 6) or hyperoxia (Pa(O(2)) > 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.

Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal Interneurons

“…The detectability index (DI; Aertsen and Gerstein, 1985) was calculated for each correlogram as the peak (or trough) relative to average background activity (calculated over 12 ms before the trigger), divided by the SD. Features were considered significant if the DI was Ͼ3 (Melssen and Epping, 1987), and only significant features in the positive direction were counted.…”

“…Features were considered significant if the DI was Ͼ3 (Melssen and Epping, 1987), and only significant features in the positive direction were counted. Peaks or troughs are consistent with functional excitation or inhibition between the trigger and target neurons, respectively (Kirkwood, 1979;Aertsen and Gerstein, 1985). Summary graphs were expressed as the number of positive cross-correlogram features (CCs) expressed as a percentage of the total number of possible features (i.e., based on the total number of recorded cells at that time point).…”

“…Significant features (i.e., peaks and troughs) were identified as departures in the cross-correlation histogram Ͼ3 SD above the background (Aertsen and Gerstein, 1985;Melssen and Epping, 1987;Aertsen et al, 1989). Positive (Fig.…”

Time-dependent modulation of carotid body afferent activity during and after intermittent hypoxia

“…Other phenomena can be elicited by repeated bouts of hypoxia, including progressive augmentation, where the ventilatory response to each successive bouts increases, and longterm facilitation (LTF), where ventilation is often elevated for up to several hours on return to normoxia (21, 24, 30). These time-dependent phenomena may have profound effects on the stability of the respiratory system; consequently, the neuronal mechanisms responsible have been the focus of considerable interest.Time-dependent ventilatory responses to hypoxia have largely been attributed to central mechanisms (5,27,29), triggered by the barrage of afferent input from the carotid bodies and/or through the direct effect of hypoxia on central neuronal circuits (3,28,33). However, some have argued that time-dependent changes in carotid body output may have a more direct role (24).…”

“…Time-dependent ventilatory responses to hypoxia have largely been attributed to central mechanisms (5,27,29), triggered by the barrage of afferent input from the carotid bodies and/or through the direct effect of hypoxia on central neuronal circuits (3,28,33). However, some have argued that time-dependent changes in carotid body output may have a more direct role (24).…”