Dynamic Changes in Glottal Resistance during Exposure to Severe Hypoxia in Neonatal Rats In Situ

Abstract

The neural control of respiratory airflow via the vocal fold is characterized by inspiratory abduction and postinspiratory (early expiratory) adduction causing decreases and increases in glottal resistance, respectively. The postinspiratory increase in glottal resistance plays a major role in braking the speed of expiratory airflow, to act against the high recoil pressure of the neonatal rat lung. In the present study, we investigated changes in upper airway patency during severe hypoxia in neonatal rats. We measured dynamic changes in subglottal pressure during normoxic and hypoxic conditions in an arterially perfused brainstem preparation in which we could control gas tensions accurately. Initially, hypoxia (5% O 2 , 5% CO 2 , and 90% nitrogen) produced an excitatory response in phrenic nerve activity accompanied by augmentation of both inspiratory-related glottal dilation and postinspiratory glottal constriction. Later, during the early stages of hypoxia-induced respiratory depression and initiation of gasping, we observed a massive reduction of the respiratory modulation of glottal resistance. In most preparations, this was transient and replaced by a paradoxic inspiratory-related glottal constriction. We propose that during severe hypoxia in the in situ preparation, paradoxic inspiratory glottal constriction can be observed during gasping, and this may impair ventilation despite the persistence of rhythmic contractions of the respiratory muscles. The latter is of clinical interest, because this may relate to the finding of cot death victims who died as a result of upper airway obstruction but without apparent apnea or rebreathing. Classically, hypoxia triggers a biphasic respiratory response that consists of an initial augmentation, then a marked depression of ventilation; this is followed by gasping until death (1). The characteristics of the hypoxic ventilatory response undergoes postnatal maturation (2). For example, in neonates, the early increase in respiration in response to hypoxia is less pronounced (2). However, neonates have a remarkable tolerance to hypoxia and robust mechanisms for autoresuscitation after hypoxia-induced respiratory depression (3-5). A major component for successful autoresuscitation is gasping (4,5), a breathing pattern triggered during marked hypoxia or anoxia. Because hypoxia is a common complication in the human neonate (3), a knowledge of the precise physiologic response to hypoxia is of clinical interest.Gasping is a unique breathing pattern defined as having a decrementing inspiratory discharge (as opposed to the augmenting pattern of eupnea) and a synchronization of inspiratory discharges in cranial (vagal, hypoglossal) and phrenic motor outflows (6 -8). In eupnea, there is a highly coordinated initiation of the motor pattern sequence of upper airway and respiratory pump motor activity such that the latter is temporally delayed so that decrease of upper airway resistance can precede the onset of lung inflation. This being the case, the respiratory cycle can be divided in...

Optical imaging of medullary ventral respiratory network during eupnea and gasping In situ

“…Evidence for the latter mechanism has been reported previously (Busselberg et al ., 2001; Markstahler et al ., 2002; Dutschmann & Paton, 2002). It has also been shown that post‐inspiratory activity is lost during hypoxic‐induced gasping (Dutschmann & Paton, 2005) and that post‐inspiratory neurons shift their phase of activation to coincidence with inspiration (Paton et al ., 2006). These previous results, in conjunction with the present data, support the notion that a shift from eupnea to gasping results in a reconfiguration of the respiratory network (i.e.…”

Upper Airway Dysfunction of Tau-P301L Mice Correlates with Tauopathy in Midbrain and Ponto-Medullary Brainstem Nuclei

“…This phenomenon was reported to occur specifically after blockade of brainstem glycinergic neurotransmission (Dutschmann and Paton, 2002a,b) and during severe hypoxia (Dutschmann and Paton, 2005). However, the verification of potentially reduced glycinergic inhibition within the ponto-medullary brainstem of Tau-P301L mice requires future experimental analysis.…”

Opioids prolong and anoxia shortens delay between onset of preinspiratory (pFRG) and inspiratory (preBötC) network bursting in newborn rat brainstems

“…Similar to opioids, inspiratory activities in newborns are depressed by severe hypoxia leading to tissue anoxia [1,3,4,15,17]. The latter studies and related work cited in these reports showed that breathing in a variety of newborn animal species continues at greatly reduced rate for anoxia periods >30 min, in particular in rodents, whereas they stop in adults after few minutes of oxygen depletion.…”