比格犬中度急性呼吸窘迫综合征模型中呼吸机所致肺损伤与肺应变的关系研究

Acute respiratory distress syndrome (ARDS) is a common severe disorder and may be the most frequent complication of respiratory infectious diseases such as H7N9. Mechanical ventilation has greatly improved the prognosis of patients with ARDS. However, the mortality is still as high as 40%. Improper mechanical ventilation may cause ventilator-induced lung injury (VILI).In order to reduce the occurrence of VILI, plateau airway pressure and tidal volume were monitored and controlled within the “rational” ranges. In fact, whether the airway pressure or tidal volume will cause VILI ultimately depends on whether they induce the unphysiological lung stress and strain. Howerver, it is still unclear whether VILI occurs with the increase of lung strain linearly in ARDS patients or animal models. Our preliminary study with canine ARDS models have shown that VILI does not develop proportionally to the applied lung strain, but only when a critical threshold of lung strain (about 1.5 ～2.0) is reached/overcome. It is of greater significance to find some evidence implying VILI may start appearing when lung strain is lower than 1.5, which needs to be researched further . We would like to recruit moderate beagle dog ARDS models, with narrower research scope and group interval of lung strain, and prolong the time of mechanical ventilation appropriately, to further search for the lung strain “inflection point” of VILI occurrence and find the "safe scope " of lung strain in mechanical ventilation. These will contribute to reduce VILI and provide the basis for individualized lung protective ventilation.

急性呼吸窘迫综合征（ARDS）是常见的急危重症，也是H7N9等呼吸道传染性疾病的严重并发症。机械通气改善了ARDS患者的预后，但死亡率仍高达40%以上。不恰当的机械通气易引起呼吸机所致肺损伤（VILI），临床上通过监测、控制气道平台压及潮气量等以减少VILI的发生。事实上，气道压或潮气量是否导致VILI最终取决于是否引起非生理性的肺应变和应力。但目前尚不明确ARDS中VILI是否随肺应变增加而成线性增加，前期研究显示犬ARDS模型中VILI的发生与肺应变不成线性关系，而是存在肺应变拐点，拐点可能位于1.5～2.0之间，也有数据显示肺应变未超过1.5时即开始出现VILI。我们拟使用ARDS动物模型，缩小肺应变的研究范围及分组组距并延长机械通气时间，进一步寻找VILI发生的肺应变拐点及机械通气中肺应变的“安全范围”，为减少VILI及研究个体化肺保护性通气提供依据。

急性呼吸窘迫综合征（ARDS）是临床常见的急危重症疾病，机械通气使ARDS患者的预后得到了极大改善，不恰当的机械通气易引起呼吸机所致肺损伤（VILI），VILI的发生机制尚未达成共识，近年来随着呼吸力学研究的深入，肺应变可能才VILI的发生中起到关键作用，本研究在前期研究基础之上使用中度急性呼吸窘迫综合征（ARDS）动物模型，以肺应变值为参考依据选择潮气量，细化分组，以肺组织病理学评分、VILI相关早期炎症指标、动物存活时间及72小时生存率、呼吸动力学参数、肺部影像学改变等参数为观察指标，进一步寻找VILI发生的肺应变拐点及机械通气中肺应变的“安全范围”。我们的研究发现随着肺应变的增加，实验动物的生存时间明显缩短，肺水肿加剧、肺组织湿干比明显增加，尤其当肺应变超过1.5时为甚，提示肺应变引起VILI的拐点为1.5，建议在实施肺保护性通气时引入对肺应变的监测，其源于本研究发现即使同是中度ARDS模型，其剩余的功能残气量（FRC）却存在着巨大的差异，因此传统肺保护性通气基于理想体重计算潮气量的理念不能兼顾FRC的个体差异。研究建立了实时浓度监测氦气稀释床旁检测FRC法，与金标准的CT法相比，具有好的准确性和精度，且具有良好的重复性。本研究还检测了实验前后血清可溶性血小板血管内皮细胞黏附分子等炎症标记物的检测，为后续研究肺应变诱导VILI发生的分子生物学机制奠定了良好的基础。目前本研究发表相关论著6篇，尚有论著正在发表之中，培养硕士研究生3人，2人已毕业，1人在读，项目总投入23万，支出合理，尚有部分节余，剩余经费用于本研究的后续研究。