Comparison of the effects of moderate and severe hypercapnic acidosis on ventilation-induced lung injury.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. dachao_1980@126.com.|Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China. dachao_1980@126.com.
Wanchao
W
Yang
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. yueziyong@126.com.|Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China. yueziyong@126.com.
Ziyong
Z
Yue
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. cuixiaoguang@hotmail.com.|Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China. cuixiaoguang@hotmail.com.
Xiaoguang
X
Cui
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. gyp721110@yahoo.com.cn.|Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China. gyp721110@yahoo.com.cn.
Yueping
Y
Guo
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. zhanglili_80@126.com.|Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China. zhanglili_80@126.com.
Lili
L
Zhang
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. zhouhuacheng@163.com.|Education Department of Heilongjiang Province, Anesthesiology Key Laboratory, Harbin Medical University, Harbin, Heilongjiang Province, China. zhouhuacheng@163.com.
Huacheng
H
Zhou
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University; Anesthesiology Key Laboratory, Harbin Medical University, Harbin, 150086, China. Wenzhili9@126.com.
Wenzhi
W
Li
D000142:Acidosis, Respiratory / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D004195:Disease Models, Animal; D006935:Hypercapnia / Q000378:metabolism* / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011659:Pulmonary Gas Exchange / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055397:Ventilator-Induced Lung Injury / Q000517:prevention & control*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002245:Carbon Dioxide