The effects of mild hypoxaemia on hypoglossal motoneurone activity in neonates

Introduction: Apneic episodes and consequent hypoxaemia are common features of breathing in high- risk neonates. Apneas of central origin (no respiratory effort) usually terminate with an obstructive component due to collapse of the upper airway. The genioglossus muscle, the main protruder muscle of the tongue, plays a crucial role in maintaining upper airway patency by opposing the negative intra-airway pressure generated during contraction of the diaphragm and by preventing the tongue blocking the oropharyngeal opening. In adults, the respiratory-related activity of the hypoglossal nerve (the motoneurone of the genioglossus) increases during hypoxaemia in order to maintain upper airway patency. However, in neonates it has been shown that the genioglossus muscle during hypoxia is age-related and this increased activity is not sustained. In neonates, little is known about how the hypoglossal motoneurones respond to hypoxaemia and the role of hypoglossal motoneurones during hypoxia in the maintenance of upper airway patency. Aim: The aim of this study was to determine the effects of hypoxaemia on hypoglossal motoneurones in neonates. Methods: Extracellular and intracellular recordings were made from hypoglossal motoneurones in vagotomized and vagi-intact neonatal kittens during normoxia and hypoxia. Results: The results showed: (1) the majority of hypoglossal motoneurones either decreased their discharge frequency or had only a transient increase during hypoxia. (2) During intracellular recordings, the membrane potential showed a sustained depolarisation during hypoxaemia in most cases and respiratory-related rhythmic EPSP activity was reduced in amplitude. The membrane impedance of these motoneurones increased and the excitability was reduced. (3) During upper airway stimulation, the amplitude of the laryngeal-evoked potentials was reduced during hypoxia. Conclusions: My results demonstrate that, in neonates, hypoglossal motoneurone activity is inhibited during hypoxia and the hypoglossal-upper airway reflexes are also inhibited. The probable consequence of such inhibition, for the newborn human infant, would be the failure of the maintenance of upper airway patency, thus leading to obstructive apnea. The mechanisms mediating the inhibition of hypoglossal motoneurones during hypoxia remain to be determined

The effects of mild hypoxia on hypoglossal motoneurones in neonates

The patency of the upper airway is dependent on the activity of the genioglossus muscle, the main protrusor muscle of the tongue. The force generated by this muscle opposes the negative intraluminal pressure produced by the contraction of the diaphragm during inspiration. Recent studies suggest that there is an immaturity in genioglossus muscle control in neonates and obstructive apnoea may occur when the activity of this muscle is reduced or absent without a corresponding decrease in the activity of the diaphragm. However, little is known of the processes mediating and influencing the activity of the hypoglossal nerve, the motor nerve of the genioglossus muscle, at this stage in development. In newborn babies, central apnoea (when there is no inspiratory effort) is usually followed by obstructive apnoea (when although there is inspiratory effort there is no inspiratory flow). It is therefore possible that hypoxia which develops during central apnoea, inhibits the activity of the genioglossus muscle and as a consequence the airway becomes obstructed. The aim of this study was therefore to determine whether hypoglossal motoneurones are inhibited during hypoxia in neonates. This study has investigated the effect of mild levels of hypoxaemia (PaO2 47.2 ± 3.8mmHg) on the activity of hypoglossal motoneurones in anaesthetized neonatal kittens (27 days old). The results showed that the majority of hypoglossal motoneurones increased in discharge frequency during hypoxia but for a substantial proportion the increase was only transient. Furthermore, some motoneurones showed a decrease in discharge frequency. Intracellular recordings showed that during similar levels of hypoxia, although a large proportion of the motoneurones were depolarized, at least some of these repolarized despite the continuing hypoxia. In addition, some hypoglossal motoneurones were hyperpolarized. This is the clearest evidence that inhibitory mechanisms, in addition to excitatory mechanisms, mediate the effects of hypoxia on hypoglossal output in neonates. Furthermore, the results suggest that hypoxia has an effect on the hypoglossal motoneurones independently of, or in addition to, its effect through respiratory rhythm. In some preliminary studies, the transmembrane input resistance increased during the hyperpolarization in response to hypoxia. One possibility is that the inhibition is mediated by the removal of an excitatory input. If the inhibition found in this study occurs in human babies it may be a compounding factor in apnoeas of the newborn