吸气和呼气肌肉活动对ARDS机械通气影响及其机制的实验研究

Abstract(limited to 800 words)：. In recent years, whether spontaneous breathing (SB) should be preserved in the early phase of ARDS has been intensively debated. It has been proved that SB with the activity of diaphragm during mechanical ventilation is associated with beneficial effects in better aeration and less atelectasis in lung dependent zones, as well as less hyperinflation in nondependent lung zones in ARDS; Improving gas exchange，global hemodynamics and organ perfusion ；Preventing ventilator-induced diaphragmatic dysfunction(VIDD)；Decreasing ventilator-associated lung injury (VALI). Thus, some researchers have claimed that SB should be preserved even in the most severe cases of ARDS.Expiration in mechanical ventilation is a passive phenomenon produced due to the lung elastic recoil forces. However, in the presence of increased respiratory driving, expiratory muscles, especially the abdominal muscles may actively participate in breath and increase intra-abdominal pressure (IAP). It has been proved that the increase of IAP even 10 cmH2O may have injurious impacts on organ functions and aggravate lung damage. Caironi et al has recently proved that the amount of lung cyclically recruitment and decruitment leads to the increase of mortality in ARDS patients. In view of the advantages and disadvantages of spontaneous breathing during mechanical ventilation in patients with ARDS, we hypothesized that activity of inspiratory muscles (diaphragm) had beneficial effects, while activity of expiratory muscles (abdominal muscle) had adverse effect. So, in animal model, we paralyzed the expiratory muscle by epidural anesthesia and paralyzed inspiratory muscle by phrenic nerve paralysis to established preserving diaphragm (inspiratory muscle) activity model and preserving abdominal muscles (expiratory muscle) model respectively. So as to explore the impacts and mechanism of inspiratory and expiratory muscles activities during mechanical ventilation in ARDS animal model and to test the hypothesis that deep sedation or paralysis might be replaced by the strategy of expiratory muscles paralysis through epidural anesthesia.

近年来，关于急性呼吸窘迫综合征（ ARDS） 机械通气患者是否应该保留自主呼吸存在着广泛的争议。有研究认为重度ARDS 患者机械通气中也应保留自主呼吸；而有研究认为完全肌松具有肺保护作用。鉴于目前 ARDS 机械通气中保留自主呼吸存在利和弊的争论，本课题在ARDS动物模型中，通过硬膜外麻醉松弛呼气肌肉和膈神经封闭方法松弛吸气肌肉，分别形成保留膈肌（吸气肌肉）活动模型和保留腹肌（呼气肌肉）活动模型。在上述模型上探索吸气和呼气肌肉活动对肺的氧合、肺容量、肺损伤和炎症介质的影响，从而阐明自主呼吸中吸气和呼气肌肉对ARDS机械通气的效果影响及其相关机制。探讨改变既往呼吸肌肉“全”或“无”方式，在ARDS机械通气中采用单独麻痹吸气或呼气肌肉，从而保留自主呼吸的优点，避免其缺点， 达到肺保护性通气目的，减少临床大剂量镇静肌松药物的应用。本课题为ARDS机械通气相关性肺损伤防治提供新思路。

急性呼吸窘迫综合征（ARDS）是临床常见危重病，有创机械通气是ARDS患者重要的支持治疗手段。然而，机械通气在提供有效呼吸支持治疗的同时, 应用不当可能引起机械通气相关性肺损伤（VALI）。尽管目前有获得广泛认可的小潮气量（LTV）、低气道平台压、最佳呼气末正压（PEEP）、允许性高碳酸血症（PHC）等为核心的机械通气治疗策略，但ARDS机械通气患者死亡率仍然高达30%～60%。因此，探讨肺保护性通气策略具有重要的临床意义。近年以来，关于ARDS机械通气患者是否应该保留自主呼吸存在着广泛的争议。有研究表明，保留自主呼吸膈肌活动能防止重力依赖区肺不张，降低非重力依赖区的高充气，从而改善氧合，减轻肺损伤，呼气是被动现象，主要依靠肺及胸廓的弹性回缩力。然而，在低氧及酸中毒等诱导的呼吸驱动增高的情况之下，腹肌的收缩可能增加腹内压。增高的腹内压降低机械通气时呼气末的跨肺压，降低呼气末肺容量，导致导致部分肺泡在呼吸周期中复闭合和开放，增加肺剪切伤。鉴于目前ARDS机械通气中保留自主呼吸存在利和弊的争论，因此我们提出吸气肌肉活动对ARDS机械通气可能有肺保护作用，而呼气肌肉可能有肺损伤作用。因此，我们在动物模型中，通过硬膜外麻醉松弛呼气肌肉和膈神经封闭方法松弛吸气肌肉，分别形成保留膈肌（吸气肌肉）活动模型和保留腹部肌肉（呼气肌肉）模型。在上述模型上探索吸气肌肉和呼气肌肉活动对ARDS动物模型机械通气的效果影响及其相关机制。本研究通过油酸诱导的比格犬ARDS机械通气模型，阐明了自主呼吸中保留膈肌活动能通过增加EELV，改善氧合，减少炎性因子，减轻肺损伤；而腹肌活动可增加腹内压，降低跨肺压，减少EELV，氧合恶化，肺损伤加重。上述结果提示，ARDS机械通气模型中，自主呼吸的吸气肌肉活动与呼气肌肉活动对机械通气的作用不同，保留吸气肌肉（膈肌）活动可以产生有利作用，而保留呼气肌（腹肌）的活动可以产生不利的作用。因此，在ARDS机械通气患者中采用硬膜外麻醉松弛呼气肌肉代替完全镇静肌松的通气策略，可以保留自主呼吸的优点，避免其不利作用，是否能应用于临床值得进一步深入研究。

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