Yang Wanchao, Yue Ziyong, Cui Xiaoguang, Guo Yueping, Zhang Lili, Zhou Huacheng, Li Wenzhi
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China.
Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China.
BMC Anesthesiol. 2015 Apr 30;15:67. doi: 10.1186/s12871-015-0050-8.
We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 "doses" (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis.
Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined.
In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p < 0.001), but improved by MHA (379.9 ± 34.5 mmHg) and SHA (298.6 ± 35.3 mmHg). The lung injury score in the SHA group (7.8 ± 1.6) was lower than the NC group (11.8 ± 2.3, P < 0.05) but was higher than the MHA group (4.4 ± 1.3, P < 0.05). Compared with the NC group, after 4 h of high pressure ventilation, the MHA and SHA groups had decreases in MPO activity of 67% and 33%, respectively, and also declined the levels of TNF-α (58% versus 72%) and MIP-2 (76% versus 60%) in the BALF. Additionally, both hypercapnic acidosis groups reduced stretch-induced NF-κB activation (p < 0.05) and significantly decreased lung ICAM-1 expression (p < 0.05).
Moderate hypercapnic acidosis (PaCO2 maintained at 80-100 mmHg) has a greater protective effect on high-pressure ventilation-induced inflammatory injury. The potential mechanisms may involve alterations in NF-κB activity.
我们已经证明，高碳酸血症性酸中毒（动脉血二氧化碳分压[PaCO₂]为80 - 100 mmHg）可预防大鼠呼吸机诱导的肺损伤。然而，关于合适的目标PaCO₂ ，或者更高的二氧化碳“剂量”（PaCO₂ > 100 mmHg）是否具有此效应仍存在不确定性。我们希望确定严重急性高碳酸血症性酸中毒是否能减轻牵张诱导的损伤，以及核因子κB（NF - κB）在急性高碳酸血症性酸中毒效应中的作用。
54只大鼠采用压力控制通气模式通气4小时，设定吸气峰压（PIP）为30 cmH₂O。立即给予二氧化碳与氧气的混合气体（吸入二氧化碳浓度[FiCO₂]=4 - 5%、FiCO₂ = 11 - 12%或FiCO₂ = 16 - 17%；吸入氧浓度[FiO₂]=0.7；其余为氮气），以维持正常碳酸血症（NC）组（PaCO₂为35 - 45 mmHg）、中度高碳酸血症（MHA）组（PaCO₂为80 - 100 mmHg）和重度高碳酸血症（SHA）组（PaCO₂为130 - 150 mmHg）的目标PaCO₂ 。9只正常或未通气的大鼠作为对照。测量血流动力学、气体交换和炎症参数。然后确定NF - κB途径在高碳酸血症性酸中毒介导的高压牵张损伤保护作用中的作用。
在NC组，高压通气导致PaO₂/FiO₂从415.6（37.1）mmHg降至179.1（23.5）mmHg（p < 0.001），但MHA组（379.9±34.5 mmHg）和SHA组（298.6±35.3 mmHg）有所改善。SHA组的肺损伤评分（为7.8±1.6）低于NC组（11.8±2.3，P < 0.05），但高于MHA组（4.4±1.3，P < 0.05）。与NC组相比，高压通气4小时后，MHA组和SHA组的髓过氧化物酶（MPO）活性分别降低67%和33%，支气管肺泡灌洗液（BALF）中肿瘤坏死因子 - α（TNF - α）水平（分别为58%对72%）和巨噬细胞炎性蛋白 - 2（MIP - 2）水平（分别为76%对60%）也下降。此外，两个高碳酸血症性酸中毒组均降低了牵张诱导的NF - κB激活（p < 0.05），并显著降低肺细胞间黏附分子 - 1（ICAM - 1）表达（p < 0.05）。
中度高碳酸血症（PaCO₂维持在80 - 100 mmHg）对高压通气诱导的炎性损伤具有更大保护作用。潜在机制可能涉及NF - κB活性的改变。
