Welch Joseph F, Nair Jayakrishnan, Argento Patrick J, Mitchell Gordon S, Fox Emily J
Breathing Research and Therapeutics Centre, University of Florida, Gainesville, FL, USA.
Department of Physical Therapy, University of Florida, Gainesville, FL, USA.
J Physiol. 2022 May;600(10):2515-2533. doi: 10.1113/JP282822. Epub 2022 Apr 28.
Acute intermittent hypoxia (AIH) elicits long-term facilitation (LTF) of respiration. Although LTF is observed when CO is elevated during AIH in awake humans, the influence of CO on corticospinal respiratory motor plasticity is unknown. Thus, we tested the hypotheses that acute intermittent hypercapnic-hypoxia (AIHH): (1) enhances cortico-phrenic neurotransmission (reflecting volitional respiratory control); and (2) elicits ventilatory LTF (reflecting automatic respiratory control). Eighteen healthy adults completed four study visits. Day 1 consisted of anthropometry and pulmonary function testing. On Days 2, 3 and 4, in a balanced alternating sequence, participants received: AIHH, poikilocapnic AIH, and normocapnic-normoxia (Sham). Protocols consisted of 15, 60 s exposures with 90 s normoxic intervals. Transcranial (TMS) and cervical (CMS) magnetic stimulation were used to induce diaphragmatic motor-evoked potentials and compound muscle action potentials, respectively. Respiratory drive was assessed via mouth occlusion pressure (P ), and minute ventilation measured at rest. Dependent variables were assessed at baseline and 30-60 min after exposures. Increases in TMS-evoked diaphragm potential amplitudes were observed following AIHH vs. Sham (+28 ± 41%, P = 0.003), but not after AIH. No changes were observed in CMS-evoked diaphragm potential amplitudes. Mouth occlusion pressure also increased after AIHH (+21 ± 34%, P = 0.033), but not after AIH. Ventilatory LTF was not observed after any treatment. We demonstrate that AIHH elicits central neural mechanisms of respiratory motor plasticity and increases resting respiratory drive in awake humans. These findings may have important implications for neurorehabilitation after spinal cord injury and other neuromuscular disorders compromising breathing. KEY POINTS: The occurrence of respiratory long-term facilitation following acute exposure to intermittent hypoxia is believed to be dependent upon CO regulation - mechanisms governing the critical role of CO have seldom been explored. We tested the hypothesis that acute intermittent hypercapnic-hypoxia (AIHH) enhances cortico-phrenic neurotransmission in awake healthy humans. The amplitude of diaphragmatic motor-evoked potentials induced by transcranial magnetic stimulation was increased after AIHH, but not the amplitude of compound muscle action potentials evoked by cervical magnetic stimulation. Mouth occlusion pressure (P , an indicator of neural respiratory drive) was also increased after AIHH, but not tidal volume or minute ventilation. Thus, moderate AIHH elicits central neural mechanisms of respiratory motor plasticity, without measurable ventilatory long-term facilitation in awake humans.
急性间歇性低氧（AIH）可引发呼吸的长期易化（LTF）。尽管在清醒人类进行AIH期间二氧化碳（CO）升高时可观察到LTF，但CO对皮质脊髓呼吸运动可塑性的影响尚不清楚。因此，我们检验了以下假设：急性间歇性高碳酸血症性低氧（AIHH）：（1）增强皮质-膈神经传递（反映随意呼吸控制）；（2）引发通气LTF（反映自动呼吸控制）。18名健康成年人完成了4次研究访视。第1天包括人体测量和肺功能测试。在第2、3和4天，参与者按平衡交替顺序接受：AIHH、变碳酸血症性AIH和常碳酸血症-常氧（假刺激）。方案包括15次、每次60秒的暴露，间隔90秒的常氧期。分别使用经颅磁刺激（TMS）和颈部磁刺激（CMS）诱导膈运动诱发电位和复合肌肉动作电位。通过口腔阻断压（P ）评估呼吸驱动，并测量静息时的分钟通气量。在基线以及暴露后30 - 60分钟评估相关变量。与假刺激相比，AIHH后观察到经颅磁刺激诱发的膈电位幅度增加（+28±41%，P = 0.003），但AIH后未增加。颈部磁刺激诱发的膈电位幅度未观察到变化。AIHH后口腔阻断压也增加（+21±34%，P = 0.033），但AIH后未增加。任何处理后均未观察到通气LTF。我们证明，AIHH可引发清醒人类呼吸运动可塑性的中枢神经机制，并增加静息呼吸驱动。这些发现可能对脊髓损伤及其他影响呼吸的神经肌肉疾病后的神经康复具有重要意义。要点：急性暴露于间歇性低氧后呼吸长期易化的发生被认为依赖于CO调节——很少有人探索CO发挥关键作用的机制。我们检验了急性间歇性高碳酸血症性低氧（AIHH）增强清醒健康人类皮质-膈神经传递的假设。经颅磁刺激诱发的膈运动诱发电位幅度在AIHH后增加，但颈部磁刺激诱发的复合肌肉动作电位幅度未增加。AIHH后口腔阻断压（P ，神经呼吸驱动的指标）也增加，但潮气量或分钟通气量未增加。因此，适度的AIHH可引发呼吸运动可塑性的中枢神经机制，在清醒人类中未观察到可测量的通气长期易化。
