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We have previously documented anatomic and functional relationships between ventilatory and autonomic neural output. Therefore, we hypothesized in this study that hypoxia-induced changes in respiratory neural output are associated with changes in autonomic regulation of lower esophageal sphincter (LES) pressure. Respiratory neural output, heart rate, and LES pressure were measured before and during a 3-min exposure to 8% oxygen (balance nitrogen) in 12 3- to 7-d-old piglets. Respiratory neural output was determined from diaphragmatic electromyogram and LES pressure from an esophageal catheter. Studies were repeated after atropine administration in eight animals. Hypoxic exposure resulted in significant increases in diaphragmatic amplitude, respiratory rate, and minute diaphragmatic activity as well as heart rate. The biphasic response of diaphragm amplitude peaked at 1 min, whereas the responses of respiratory frequency and heart rate were sustained. Hypoxia caused a 50% increase in LES pressure (p < 0.05), which was eliminated by i.v. atropine administration. Development of apnea during subsequent hyperoxic exposure was always followed by a decline in LES pressure. Hypoxia-induced increase in respiratory neural output and accompanying increase in heart rate are associated with enhanced constrictive output to the LES. Blockade by atropine implicates a peripheral cholinergic mechanism for this LES response. We speculate that whereas hypoxia in the presence of enhanced respiratory neural output seems to be protective against reflux, decreased respiratory drive and accompanying apnea may be associated with a decline in LES tone and predispose to gastroesophageal reflux.

The respiratory network that generates rhythmic activity is continuously subjected to excitatory and inhibitory inputs which regulate tidal breathing and respiratory timing: inspiratory (Ti) and expiratory (Te) duration. Recently we have shown in unrestrained, 5 day (but not 3 wk old) rat pups, that hypercapnia induced increases in tidal volume are accompanied by reduction in frequency due to an increase in Te. To identify if this maturational change in timing response to CO2 is central or peripheral in origin, we examined the effect of graded increases in inhaled CO2 on phrenic activity in decerebrate, vagotomized, paralyzed, and mechanically ventilated rat pups at 4-6 (n=8), 12-17 (n=9), and 36-40 (n=8) days. Hypercapnia always induced an increase in peak phrenic activity, which was associated with a CO2 concentration-dependent increase in Te at 4-6 but not 12-17 or 36-39 days (Fig). Hypercapnia had no significant effect on Ti. These results indicate that in early postnatal life CO2 increases phrenic output in parallel with a prolongation of Te which is centrally mediated and not related to changes in vagal or upper airway reflexes. We postulate that in the youngest animals, prolongation of Te during hypercapnia provides sufficient time to empty the lungs, regulate functional residual capacity and optimize work of breathing. Excessive prolongation of Te during hypercapnia, however, might compromise the ventilatory response.

Respiratory center drive is most accurately reflected from the steepest rise of the diaphragmatic EMG (Edi) at inspiratory onset. This parameter equates to peak acceleration of diaphragmatic activation (PaEdi) and reflects diaphragmatic recruitment whereas further rise of Edi amplitude (EdiA) signifies continued neuronal discharge. Calibrated respiratory inductive plethysmography (RIP) provides rib cage (RC), abdominal (AB) and their sum(Vt) waveforms noninvasively. We therefore tested the hypothesis that RIP derived acceleration signals (PaRC, PaAB or PaVt) could be used as measures of respiratory drive by validation with PaEdi during unimpeded breathing and obstructed efforts. Five newborn piglets were lightly anesthetized and allowed to breathe spontaneously through cuffed endotracheal tubes. A wire electrode was inserted into the diaphragm using a percutaneous, subcostal approach and RIP transducers applied to the RC and AB compartments. Peak acceleration from RIP waveforms was measured as the highest value in a window range of±300 msec around the mechanical onset of inspiration. The same window was used for PaEdi. Data were displayed and stored on a Respitrace PT16 recorder (Nims, Miami Beach, FL) for subsequent analysis with RespiEvents software. Interventions included 7% CO2 rebreathing and end expiratory obstruction of the endotracheal tube over 2-4 efforts. For CO2 rebreathing, a correlation matrix was calculated for each animal and the means(SD) are listed below; *indicates r with p

Maturation of Ventilatory Responses to Hypoxia, Hypercapnia, and Combined Hypoxia and Hypercapnia in Rats. † 1446