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

BACKGROUND: We have proved that hypercapnic acidosis (a PaCO(2) of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO(2) or if greater CO(2) “doses” (PaCO(2) > 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 cmH(2)O. A gas mixture of carbon dioxide with oxygen (FiCO(2) = 4-5%, FiCO(2) = 11-12% or FiCO(2) = 16-17%; FiO(2) = 0.7; balance N(2)) was immediately administered to maintain the target PaCO(2) in the NC (a PaCO(2) of 35-45 mmHg), MHA (a PaCO(2) of 80-100 mmHg) and SHA (a PaCO(2) 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 PaO(2)/FiO(2) 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 (PaCO(2) 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.