RATIONALE: The original in vivo study of ventilator-induced lung injury by Webb and Tierney (1974) reported that high VT with zero PEEP caused overwhelming lung injury, subsequently shown by others to be due to lung shear stress. OBJECTIVE: To reproduce the lung injury and edema in the ‘Webb and Tierney’ study and investigate the mechanism. METHODS: Sprague-Dawley rats (≈400 g) received mechanical ventilation for 60 min according to the protocol of Webb and Tierney (14/0, 30/0, 45/10, 45/0 cmH2O). Additional series of experiments (20 min duration, to ensure all animals survived) were studied to assess permeability (4/group), echocardiography (4/group), and right and left ventricular pressure (5 and 4/group, respectively). MEASUREMENTS AND MAIN RESULTS: The original Webb & Tierney results were replicated in terms of lung/body weight ratio (45/0 > 45/10 ≈ 30/0 ≈ 14/0; P<0.05), and histology. In 45/0, pulmonary edema was overt and rapid, with survival less than 30 min. In 45/0 (but not 45/10), there was an increase in microvascular permeability, cyclical abolition of preload, and progressive dilation of the right ventricle. While left ventricular end-diastolic pressure decreased in 45/10, it increased in 45/0. CONCLUSIONS: In a classic model of VILI high peak pressure (and zero PEEP) causes respiratory swings (obliteration during inspiration) in RV filling and pulmonary perfusion, and ultimate RV failure and dilation. Pulmonary edema was due to increased permeability, augmented by a modest (approximately 40%) increase in hydrostatic pressure. The mechanism of cor pulmonale is uncertain but might be due to pulmonary microvascular injury from cyclic interruption/exaggeration of flow.

中文翻译：

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呼吸机诱发的肺损伤中的不良心肺相互作用

理由：Webb和Tierney（1974）最初对呼吸机引起的肺部损伤进行的体内研究报道，高VT和PEEP为零会导致压倒性肺部损伤，随后其他研究表明这是由于肺切应力引起的。目的：在“韦伯和蒂尔尼”研究中重现肺损伤和水肿，并研究其机制。方法：按照Webb和Tierney（14/0，30/0，45/10，45/0 cmH2O）的协议，对Sprague-Dawley大鼠（≈400g）进行60分钟的机械通气。研究了其他系列实验（持续20分钟，以确保所有动物均存活）以评估通透性（4个/组），超声心动图（4个/组）以及左右心室压力（分别为5个和4个/组）。测量和主要结果：原始Webb和 Tierney结果根据肺/体重比（45/0> 45/10≈30/0≈14/0； P <0.05）和组织学进行了复制。在45/0时，肺水肿明显且迅速，存活时间少于30分钟。在45/0（但不是45/10）中，微血管通透性增加，周期性取消预负荷以及右心室进行性扩张。左心室舒张末期压力降低了45/10，而升高了45/0。结论：在经典的VILI模型中，高峰值压力（和零PEEP）导致右室充盈和肺灌注引起呼吸摆动（吸气时闭塞），并最终导致右室衰竭和扩张。肺水肿是由于通透性增加，静水压适度增加（约40％）而引起的。