Simon Fraser University, Burnaby, British Columbia, Canada.
RCHF Advancing Innovation in Medicine Institute, New Westminster, British Columbia, Canada.
J Appl Physiol (1985). 2024 Nov 1;137(5):1175-1181. doi: 10.1152/japplphysiol.00884.2023. Epub 2024 Sep 12.
Patients with acute respiratory distress syndrome (ARDS) require periods of deep sedation and mechanical ventilation, leading to diaphragm dysfunction. Our study seeks to determine whether the combination of temporary transvenous diaphragm neurostimulation (TTDN) and mechanical ventilation changes the degree of diaphragm injury and cytokines concentration in a preclinical ARDS model. Moderate ARDS was induced in pigs using oleic acid, followed by ventilation for 12 h post-injury with volume-control at 8 mL/kg, positive end-expiratory pressure (PEEP) 5 cmHO, respiratory rate and [Formula: see text] set to achieve normal arterial blood gases. Two groups received TTDN: every second breath (MV + TTDN50%, = 6) or every breath (MV + TTDN100%, = 6). One group received ventilation only (MV, = 6). Full-thickness diaphragm and quadricep muscle biopsies were taken at study end. Samples were fixed and stained with hematoxylin and eosin and a point-counting technique was applied to calculate abnormal muscle area fraction. Cytokine concentrations were measured in homogenized tissue using porcine-specific enzyme-linked immunosorbent assay (ELISA) and compared with serum samples. Percentage of abnormal diaphragm tissue was different between MV [8.1% (6.0-8.8)] versus MV + TTDN50% [3.4% (2.1-4.8)], = 0.010 and MV versus MV + TTDN100% [3.1% (2.5-4.0)], = 0.005. Percentage of abnormal quadriceps tissue was not different between groups. Cytokine concentration patterns in diaphragm samples were different between all groups ( < 0.001) and the interaction between TTDN application and resultant cytokine concentration pattern was significant ( = 0.025). TTDN, delivered in synchrony with mechanical ventilation, mitigated diaphragm injury, as evidenced by less abnormal tissue in the diaphragm samples, in pigs with oleic acid-induced ARDS and is an exciting tool for lung and diaphragm-protective ventilation. This study adds to our understanding of applying transvenous diaphragm neurostimulation synchronously with mechanical ventilation by examining its effects on diaphragm muscle injury and cytokine concentration patterns in pigs with acute respiratory distress syndrome (ARDS). We observed that using this therapy for 12 h post lung injury mitigated ventilator-induced diaphragm injury and changed the pattern of cytokine concentration measured in diaphragm tissue. These findings suggest that transvenous diaphragm neurostimulation is an exciting tool for lung and diaphragm protective ventilation.
患者患有急性呼吸窘迫综合征（ARDS），需要长时间深度镇静和机械通气，这会导致膈肌功能障碍。我们的研究旨在确定经静脉膈肌神经刺激（TTDN）与机械通气联合应用是否会改变临床前 ARDS 模型中膈肌损伤和细胞因子浓度的程度。使用油酸诱导猪中度 ARDS，伤后 12 小时进行通气，容量控制为 8 mL/kg，呼气末正压（PEEP）5 cmH2O，呼吸频率和[Formula: see text]设置为实现正常动脉血气。两组接受 TTDN：每两次呼吸（MV + TTDN50%，n = 6）或每呼吸（MV + TTDN100%，n = 6）。一组仅接受通气（MV，n = 6）。研究结束时采集膈肌和股四头肌的全层活检。将标本固定、苏木精和伊红染色，并应用点计数技术计算异常肌面积分数。使用猪特异性酶联免疫吸附试验（ELISA）测量组织匀浆中的细胞因子浓度，并与血清样本进行比较。MV [8.1%（6.0-8.8）]与 MV + TTDN50% [3.4%（2.1-4.8）]相比，MV 组的膈肌异常组织百分比不同，差异有统计学意义， = 0.010 和 MV 与 MV + TTDN100% [3.1%（2.5-4.0）]， = 0.005。各组间股四头肌异常组织百分比无差异。各组膈肌样本中的细胞因子浓度模式不同（<0.001），TTDN 应用与细胞因子浓度模式的相互作用具有统计学意义（ = 0.025）。在油酸诱导的 ARDS 猪中，与机械通气同步给予 TTDN 可减轻膈肌损伤，这可通过膈肌样本中异常组织减少来证明，这是一种用于肺和膈肌保护性通气的令人兴奋的工具。这项研究通过研究经静脉膈肌神经刺激对急性呼吸窘迫综合征（ARDS）猪的膈肌肌肉损伤和细胞因子浓度模式的影响，增加了我们对与机械通气同步应用经静脉膈肌神经刺激的理解。我们观察到，在肺损伤后 12 小时使用这种治疗方法可减轻呼吸机引起的膈肌损伤，并改变膈肌组织中细胞因子浓度的模式。这些发现表明，经静脉膈肌神经刺激是一种用于肺和膈肌保护性通气的令人兴奋的工具。
