Influence of weaning modes on diaphragmatic remodeling in an animal model of ventilator-induced diaphragmatic dysfunction

机械通气（MV）是呼吸衰竭患者的一种挽救生命的干预措施。当横膈膜不活动或仅部分活动时，通气支持时间可持续数周。先前涉及动物和人类的研究证明了与MV相关的快速肌肉萎缩。膈肌的部分活动可以减少萎缩，但不能完全防止萎缩。据我们所知，所有检查膈肌激活的研究都没有模拟已经萎缩的膈肌和/或MV之前存在的损伤，尽管这在重症监护室很常见。因此，所提出的实验将检查脱机模式对经历12小时机械通气的预损伤或健康的肌肉再生的影响。两个实验设置将研究健康大鼠或肺气肿大鼠。后一种动物由于几个月的长期阻力呼吸而建立了不同的呼吸纹理。所有动物将被分配到实验组，进行MV以诱导膈肌萎缩，之后将直接或逐步重新加载隔膜。将研究萎缩、肌生成和细胞损伤的变化。由于神经肌肉阻滞剂会加重MV期间发生的病理生理学，因此将在使用健康动物的实验环境中测试这些过程。总体结果将为脱机模式的有效性提供见解，特别是在考虑ICU环境中存在其他合并症和潜在有害药物使用的情况下。

Mechanical ventilation (MV) is a life saving intervention in patients with respiratory failure. Ventilatory support time can last for weeks while the diaphragm is inactive or only partially active. Previous studies involving animals and humans demonstrate the rapid muscle atrophy associated with MV. Partial activation of the diaphragm reduces atrophy but does not prevent it completely. To our knowledge, all studies examining diaphragmatic activation did not mimic an already atrophic diaphragm and/or pre-existent injury prior to MV, although this is common in intensive care units. Therefore, the proposed experiments will examine the influence of weaning modes on the regeneration of a pre-injured or healthy diaphragmatic muscle that underwent 12 h of mechanical ventilation. Two experimental settings will investigate either healthy rats or rats with lung emphysema. Latter animals establish a differing diaphragmatic texture due to long term resistive breathing over several months. All animals will be assigned to experimental groups undergoing MV to induce diaphragmatic atrophy, after which the diaphragm will be reloaded either directly or stepwise. Changes in atrophy, myogenesis and cell damage will be investigated. Due to the fact that neuromuscular blocking agents aggravate the pathohphysiology occurring during MV, these processes will be tested in the experimental setting that uses healthy animals. Overall results will provide insight in the effectiveness of weaning modalities, especially under the consideration of an ICU setting with additional comorbidities and potentially harmful drug use .