BACKGROUND Ventilator-induced diaphragmatic dysfunction is a serious complication associated with higher ICU mortality, prolonged mechanical ventilation, and unsuccessful withdrawal from mechanical ventilation. Although neurally adjusted ventilatory assist (NAVA) could be associated with lower patient-ventilator asynchrony compared with conventional ventilation, its effects on diaphragmatic dysfunction have not yet been well elucidated. METHODS Twenty Japanese white rabbits were randomly divided into four groups, (1) no ventilation, (2) controlled mechanical ventilation (CMV) with continuous neuromuscular blockade, (3) NAVA, and (4) pressure support ventilation (PSV). Ventilated rabbits had lung injury induced, and mechanical ventilation was continued for 12 h. Respiratory waveforms were continuously recorded, and the asynchronous events measured. Subsequently, the animals were euthanized, and diaphragm and lung tissue were removed, and stained with Hematoxylin-Eosin to evaluate the extent of lung injury. The myofiber cross-sectional area of the diaphragm was evaluated under the adenosine triphosphatase staining, sarcomere disruptions by electron microscopy, apoptotic cell numbers by the TUNEL method, and quantitative analysis of Caspase-3 mRNA expression by real-time polymerase chain reaction. RESULTS Physiological index, respiratory parameters, and histologic lung injury were not significantly different among the CMV, NAVA, and PSV. NAVA had lower asynchronous events than PSV (median [interquartile range], NAVA, 1.1 [0-2.2], PSV, 6.8 [3.8-10.0], p = 0.023). No differences were seen in the cross-sectional areas of myofibers between NAVA and PSV, but those of Type 1, 2A, and 2B fibers were lower in CMV compared with NAVA. The area fraction of sarcomere disruptions was lower in NAVA than PSV (NAVA vs PSV; 1.6 [1.5-2.8] vs 3.6 [2.7-4.3], p < 0.001). The proportion of apoptotic cells was lower in NAVA group than in PSV (NAVA vs PSV; 3.5 [2.5-6.4] vs 12.1 [8.9-18.1], p < 0.001). There was a tendency in the decreased expression levels of Caspase-3 mRNA in NAVA groups. Asynchrony Index was a mediator in the relationship between NAVA and sarcomere disruptions. CONCLUSIONS Preservation of spontaneous breathing using either PSV or NAVA can preserve the cross sectional area of the diaphragm to prevent atrophy. However, NAVA may be superior to PSV in preventing sarcomere injury and apoptosis of myofibrotic cells of the diaphragm, and this effect may be mediated by patient-ventilator asynchrony.

中文翻译：

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经神经调节的通气辅助可减轻通气机引起的diaphragm肌损伤。

背景技术呼吸机诱发的diaphragm肌功能障碍是一种严重的并发症，与更高的ICU死亡率，延长的机械通气和从机械通气中途退出有关。尽管与传统通气相比，神经调节通气辅助（NAVA）可能与较低的患者-呼吸机异步性相关，但尚未充分阐明其对diaphragm肌功能障碍的影响。方法将20只日本白兔随机分为四组，（1）无通气，（2）连续神经肌肉阻滞的受控机械通气（CMV），（3）NAVA，和（4）压力支持通气（PSV）。通风的兔子诱发了肺损伤，并继续进行机械通气12 h。连续记录呼吸波形，并测量异步事件。随后，对动物实施安乐死，取出隔膜和肺组织，并用苏木精-曙红染色以评估肺损伤的程度。在腺苷三磷酸酶染色，通过电子显微镜检查肌节破裂，通过TUNEL法检测凋亡细胞数，以及通过实时聚合酶链反应定量分析Caspase-3 mRNA表达的情况下，评估隔膜的肌纤维截面积。结果CMV，NAVA和PSV之间的生理指标，呼吸参数和组织学肺损伤无显着差异。NAVA的异步事件低于PSV（中位[四分位间距]，NAVA，1.1 [0-2.2]，PSV，6.8 [3.8-10.0]，p = 0.023）。在NAVA和PSV之间，肌纤维的横截面积没有差异，但是类型1、2A，与NAVA相比，CMV和2B纤维的CMV更低。在NAVA中，肌节破裂的面积分数低于PSV（NAVA与PSV； 1.6 [1.5-2.8]与3.6 [2.7-4.3]，p <0.001）。NAVA组的凋亡细胞比例低于PSV（NAVA vs PSV； 3.5 [2.5-6.4] vs 12.1 [8.9-18.1]，p <0.001）。在NAVA组中，Caspase-3 mRNA的表达水平有降低的趋势。异步指数是NAVA和肌节破裂之间关系的中介。结论使用PSV或NAVA保留自发呼吸可以保留横diaphragm膜的横截面积，以防止萎缩。然而，在预防肌节损伤和injury肌纤维化细胞凋亡方面，NAVA可能优于PSV，并且这种效果可能是由患者-呼吸机的异步引起的。