One-hit Models of Ventilator-induced Lung Injury Benign Inflammation versus Inflammation as a By-product
One-hit Models of Ventilator-induced Lung Injury Benign Inflammation versus Inflammation as a By-product
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DOI：
10.1097/aln.0000000000001605
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发表时间：
2017-05-01
期刊：
影响因子：
8.8
通讯作者：
Uhlig, Stefan
中科院分区：
文献类型：
--
作者：
Lex, Dennis;Uhlig, Stefan
背景：传统机械通气有害影响的一个重要解释是生物创伤假说，即通气可能引发促炎症反应，从而导致肺损伤。这一假设经常在所谓的一次性模型（健康肺部过度通气）中进行研究，迄今为止，该模型未能在炎症和低氧性肺衰竭之间建立明确的联系。本研究旨在开发一种一次性生物创伤模型。方法：对小鼠（每组六只）进行通气长达 7 小时（呼气末正压 2 cm H2O）并接受 300 μl/h 的液体支持。系列_1：初始平台压力为 10、24、27 或 30 cm H2O。系列_2：通气压力为 34 cm H2O，初始平台压力为 10、24、27 或 30 cm H2O。为了研究炎症的重要性，后一组也接受了类固醇地塞米松预处理。 结果：在 7 小时内，24 只使用 27 cm H2O 或更高平台压进行通气的小鼠中，有 20 只死于灾难性肺衰竭，其特征是促炎标记物强烈增加以及肺顺应性、血压和氧合急剧下降。地塞米松预处理减少了炎症，但中位生存时间延长了 30 分钟。结论：我们的研究结果表明，耐受性良好的 24 cm H2O 通气与大多数动物因灾难性肺衰竭而致命的 27 cm H2O 通气之间存在明显区别。在前一种情况下，炎症是良性的，而在后一种情况下，炎症是一种只会加速肺衰竭的副产品。作者认为，生物创伤——当被定义为通气引起的和炎症依赖性低氧血症时——很难在小鼠一次性通气模型中进行研究，至少在 7 小时内是这样。
Background: One important explanation for the detrimental effects of conventional mechanical ventilation is the biotrauma hypothesis that ventilation may trigger proinflammatory responses that subsequently cause lung injury. This hypothesis has frequently been studied in so-called one-hit models (overventilation of healthy lungs) that so far have failed to establish an unequivocal link between inflammation and hypoxemic lung failure. This study was designed to develop a one-hit biotrauma model.Methods: Mice (six per group) were ventilated for up to 7 h (positive end-expiratory pressure 2 cm H2O) and received 300 mu l/h fluid support. Series_1: initial plateau pressures of 10, 24, 27, or 30 cm H2O. Series_2: ventilation with pressure release at 34 cm H2O and initial plateau pressure of 10, 24, 27, or 30 cm H2O. To study the significance of inflammation, the latter groups were also pretreated with the steroid dexamethasone.Results: Within 7 h, 20 of 24 mice ventilated with plateau pressure of 27 cm H2O or more died of a catastrophic lung failure characterized by strongly increased proinflammatory markers and a precipitous decrease in pulmonary compliance, blood pressure, and oxygenation. Pretreatment with dexamethasone reduced inflammation, but prolonged median survival time by 30 min.Conclusions: Our findings demonstrate a sharp distinction between ventilation with 24 cm H2O that was well tolerated and ventilation with 27 cm H2O that was lethal for most animals due to catastrophic lung failure. In the former case, inflammation was benign and in the latter, a by-product that only accelerated lung failure. The authors suggest that biotrauma-when defined as a ventilation-induced and inflammation-dependent hypoxemia-is difficult to study in murine one-hit models of ventilation, at least not within 7 h.