Hoegl Sandra, Boost Kim A, Flondor Michael, Scheiermann Patrick, Muhl Heiko, Pfeilschifter Josef, Zwissler Bernhard, Hofstetter Christian
Clinic of Anaesthesiology, University Hospital of Ludwig-Maximilians-University, D-81377 Munich, Germany.
Int J Mol Med. 2008 Apr;21(4):513-9.
Though often lifesaving, mechanical ventilation itself bears the risk of lung damage [ventilator-induced lung injury (VILI)]. The underlying molecular mechanisms have not been fully elucidated, but stress-induced mediators seem to play an important role in biotrauma related to VILI. Our purpose was to evaluate an animal model of VILI that allows the observation of pathophysiologic changes along with parameters of biotrauma. For VILI induction, rats (n=16) were ventilated with a peak airway pressure (pmax) of 45 cm H2O and end-expiratory pressure (PEEP) of 0 for 20 min, followed by an observation time of 4 h. In the control group (n=8) the animals were ventilated with a pmax of 20 cm H2O and PEEP of 4. High-pressure ventilation resulted in an increase in paCO2 and a decrease in paO2 and mean arterial pressure. Only 4 animals out of 16 survived 4 h and VILI lungs showed severe macroscopic and microscopic damage, oedema and neutrophil influx. High-pressure ventilation increased the cytokine levels of macrophage inflammatory protein-2 and IL-1beta in bronchoalveolar lavage and plasma. VILI also induced pulmonary heat shock protein-70 expression and the activity of matrix metalloproteinases. The animal model used enabled us to observe the effect of high-pressure ventilation on mortality, lung damage/function and biotrauma. Thus, by combining barotrauma with biotrauma, this animal model may be suitable for studying therapeutical approaches to VILI.
尽管机械通气常常能挽救生命，但其本身也存在导致肺损伤[呼吸机诱导的肺损伤（VILI）]的风险。其潜在的分子机制尚未完全阐明，但应激诱导的介质似乎在与VILI相关的生物创伤中起重要作用。我们的目的是评估一种VILI动物模型，该模型能够观察病理生理变化以及生物创伤参数。为诱导VILI，将大鼠（n = 16）以45 cm H2O的气道峰值压力（pmax）和0的呼气末正压（PEEP）通气20分钟，随后观察4小时。在对照组（n = 8）中，动物以20 cm H2O的pmax和4的PEEP进行通气。高压通气导致动脉血二氧化碳分压（paCO2）升高、动脉血氧分压（paO2）和平均动脉压降低。16只动物中只有4只存活了4小时，VILI肺表现出严重的宏观和微观损伤、水肿和中性粒细胞浸润。高压通气增加了支气管肺泡灌洗和血浆中巨噬细胞炎性蛋白-2和白细胞介素-1β的细胞因子水平。VILI还诱导了肺热休克蛋白-70的表达和基质金属蛋白酶的活性。所使用的动物模型使我们能够观察高压通气对死亡率、肺损伤/功能和生物创伤的影响。因此，通过将气压伤与生物创伤相结合，这种动物模型可能适合于研究VILI的治疗方法。
