Ventilatory drive and the apnea-hypopnea index in six-to-twelve year old children

BACKGROUND: We tested the hypothesis that ventilatory drive in hypoxia and hypercapnia is inversely correlated with the number of hypopneas and obstructive apneas per hour of sleep (obstructive apnea hypopnea index, OAHI) in children. METHODS: Fifty children, 6 to 12 years of age were studied. Participants had an in-home unattended polysomnogram to compute the OAHI. We subsequently estimated ventilatory drive in normoxia, at two levels of isocapnic hypoxia, and at three levels of hyperoxic hypercapnia in each subject. Experiments were done during wakefulness, and the mouth occlusion pressure measured 0.1 seconds after inspiratory onset (P(0.1)) was measured in all conditions. The slope of the relation between P(0.1 )and the partial pressure of end-tidal O(2 )or CO(2 )(P(ET)O(2 )and P(ET)CO(2)) served as the index of hypoxic or hypercapnic ventilatory drive. RESULTS: Hypoxic ventilatory drive correlated inversely with OAHI (r = -0.31, P = 0.041), but the hypercapnic ventilatory drive did not (r = -0.19, P = 0.27). We also found that the resting P(ET)CO(2 )was significantly and positively correlated with the OAHI, suggesting that high OAHI values were associated with resting CO(2 )retention. CONCLUSIONS: In awake children the OAHI correlates inversely with the hypoxic ventilatory drive and positively with the resting P(ET)CO(2). Whether or not diminished hypoxic drive or resting CO(2 )retention while awake can explain the severity of sleep-disordered breathing in this population is uncertain, but a reduced hypoxic ventilatory drive and resting CO(2 )retention are associated with sleep-disordered breathing in 6–12 year old children

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

<p>Abstract</p> <p>Background</p> <p>Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.</p> <p>Methods</p> <p>Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂= 80%) and hyperoxic (FiO₂= 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.</p> <p>Results</p> <p>Hypoxia enhanced hyperpnoea-induced P_di,twand P_ga,twreductions both immediately after hyperpnoea (P_di,tw: normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw: normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all <it>P </it>< 0.05) and after 30 min of recovery (P_di,tw: normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw: normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all <it>P </it>< 0.05). No significant difference in P_di,twor P_ga,twreductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.</p> <p>Conclusions</p> <p>These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂transport as during exercise in altitude or in hypoxemic patients.</p

Active Zone Protein Bassoon Co-Localizes with Presynaptic Calcium Channel, Modifies Channel Function, and Recovers from Aging Related Loss by Exercise

The P/Q-type voltage-dependent calcium channels (VDCCs) are essential for synaptic transmission at adult mammalian neuromuscular junctions (NMJs); however, the subsynaptic location of VDCCs relative to active zones in rodent NMJs, and the functional modification of VDCCs by the interaction with active zone protein Bassoon remain unknown. Here, we show that P/Q-type VDCCs distribute in a punctate pattern within the NMJ presynaptic terminals and align in three dimensions with Bassoon. This distribution pattern of P/Q-type VDCCs and Bassoon in NMJs is consistent with our previous study demonstrating the binding of VDCCs and Bassoon. In addition, we now show that the interaction between P/Q-type VDCCs and Bassoon significantly suppressed the inactivation property of P/Q-type VDCCs, suggesting that the Ca2+ influx may be augmented by Bassoon for efficient synaptic transmission at NMJs. However, presynaptic Bassoon level was significantly attenuated in aged rat NMJs, which suggests an attenuation of VDCC function due to a lack of this interaction between VDCC and Bassoon. Importantly, the decreased Bassoon level in aged NMJs was ameliorated by isometric strength training of muscles for two months. The training increased Bassoon immunoreactivity in NMJs without affecting synapse size. These results demonstrated that the P/Q-type VDCCs preferentially accumulate at NMJ active zones and play essential role in synaptic transmission in conjunction with the active zone protein Bassoon. This molecular mechanism becomes impaired by aging, which suggests altered synaptic function in aged NMJs. However, Bassoon level in aged NMJs can be improved by muscle exercise

GABAA and glycine receptors in regulation of intercostal and abdominal expiratory activity in vitro in neonatal rat

The roles played by GABAA and glycine receptors in inspiratory-expiratory motor co-ordination and in tonic inhibitory regulation of expiratory motor activity were studied using brainstem-spinal cord (-rib) preparations from neonatal rats. Inspiratory activity was recorded from the C4 ventral root. Expiratory activity in internal intercostal muscle, internal oblique muscle or T13 ventral root was evoked by a decrease in perfusate pH from 7.4 to 7.1 (i.e. from normal to low pH conditions) and was limited to the first part of the expiratory phase. Under low pH conditions, bath application of 10 μm bicuculline, a GABAA receptor antagonist, caused the inspiratory burst to overlap the expiratory burst in 2/7 preparations. Overlapping of the expiratory burst with the inspiratory burst was observed in 7/7 preparations made under 10 μm bicuculline. Furthermore, such preparations exhibited expiratory bursts under bicuculline-containing normal pH conditions. Local application of 10 μm bicuculline to the brainstem under normal pH conditions evoked expiratory bursts, some of which overlapped the inspiratory bursts. Picrotoxin, another antagonist of the GABAA receptor, had similar effects. Under normal pH conditions, application of strychnine (0.2– 2.0 μm; a glycine receptor antagonist) to the brainstem did not evoke expiratory bursts. On subsequent application of strychnine-containing low pH solution, expiratory bursts were evoked and some (0.5 μm) or all (2.0 μm) of these overlapped the inspiratory burst. Simultaneous application of picrotoxin and strychnine to the brainstem evoked expiratory bursts that overlapped the inspiratory bursts and a subsequent decrease in perfusate pH to 7.1 increased the frequency of the respiratory rhythm. It was a characteristic finding that the duration of the expiratory burst exceeded that of the inspiratory burst under control low pH conditions. This remained true during concurrent blockade of GABAA and glycine receptors. The results suggest that in the in vitro preparation from neonatal rats: (1) GABAA and glycine receptors within the brainstem play important roles in the co-ordination between inspiratory and expiratory motor activity, (2) tonic inhibition via GABAA receptors, but not glycine receptors, plays a role in the regulation of expiratory motor activity and (3) inspiratory and expiratory burst termination is independent of both GABAA and glycine receptors