Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, Netherlands.
Respir Res. 2013 Sep 18;14(1):92. doi: 10.1186/1465-9921-14-92.
Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex vivo, through calcium (Ca2+)-dependent mechanism.
N = 35 male anesthetized and paralyzed male Wistar rats were randomized to intratracheal instillation of 2 mg/kg LPS or nothing and subsequent MV with lung-protective settings (low tidal volume (Vt) of 6 mL/kg and 5 cmH2O positive end-expiratory pressure (PEEP)) or injurious ventilation (high Vt of 19 mL/kg and 1 cmH2O PEEP) for 4 hours. Myocardial function ex vivo was evaluated in a Langendorff setup and Ca2+ exposure. Key mediators were determined in lung and heart at the mRNA level.
Instillation of LPS and high Vt MV impaired gas exchange and, particularly when combined, increased pulmonary wet/dry ratio; heat shock protein (HSP)70 mRNA expression also increased by the interaction between LPS and high Vt MV. For the heart, C-X-C motif ligand (CXCL)1 and Toll-like receptor (TLR)2 mRNA expression increased, and ventricular (LV) systolic pressure, LV developed pressure, LV +dP/dtmax and contractile responses to increasing Ca2+ exposure ex vivo decreased by LPS. High Vt ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca2+ responses.
Injurious MV by high Vt aggravates the effects of intratracheal instillation of LPS on myocardial dysfunction, possibly through enhancing myocardial inflammation via pulmonary release of HSP70 stimulating cardiac TLR2, not involving Ca2+ handling and sensitivity.
机械通气（MV）可能导致呼吸机引起的肺损伤（VILI），并可能因此导致致命的多器官衰竭。我们测试了这样一个假设，即脂多糖（LPS）预先损伤的肺的损伤性 MV 会通过钙（Ca2+）依赖性机制在体外引起心肌炎症和进一步的功能障碍。
N = 35 只麻醉和麻痹的雄性 Wistar 大鼠随机分为气管内滴注 2mg/kg LPS 或无处理组，并随后进行保护性通气（低潮气量（Vt）为 6ml/kg 和 5cmH2O 呼气末正压（PEEP））或损伤性通气（高 Vt 为 19ml/kg 和 1cmH2O PEEP）4 小时。在 Langendorff 装置中评估心肌功能，并进行 Ca2+暴露。在肺和心脏中测定关键介质的 mRNA 水平。
LPS 滴注和高 Vt MV 均损害了气体交换，特别是当两者结合时，增加了肺湿/干比；热休克蛋白（HSP）70 的 mRNA 表达也因 LPS 和高 Vt MV 的相互作用而增加。对于心脏，C-X-C 基序配体（CXCL）1 和 Toll 样受体（TLR）2 的 mRNA 表达增加，心室（LV）收缩压、LV 发展压、LV + dP/dtmax 和对增加的 Ca2+暴露的收缩反应降低由 LPS。高 Vt 通气加重了 LPS 对心肌炎症和功能障碍的影响，但对 Ca2+反应没有影响。
高 Vt 的损伤性 MV 通过肺释放 HSP70 刺激心脏 TLR2 增强心肌炎症，可能通过增强心肌炎症，从而加重气管内滴注 LPS 对心肌功能障碍的影响，而不涉及 Ca2+处理和敏感性。
