Therapeutic hypercapnia reduces pulmonary and systemic injury following invivo lung reperfusion

Permissive hypercapnia, involving tolerance to elevated Pacer is associated with reduced acute lung injury (ALI), thought to result from reduced mecha nical stretch, and improved outcome in ARDS. However, deliberately elevatin g inspired CO2 concentration alone (therapeutic hypercapnia, TH) protects a gainst ALI in ex vivo models. We investigated whether TH would protect agai nst Atl in an in vivo model of lung ischemia-reperfusion (IR). Anesthetized open chest rabbits were ventilated (standard eucapnic settings), and were randomized to TH (FICO2 0.12) Versus control (FICO2 0.00). Pao, and arteria l pH values achieved in the TH versus CON groups were 101 +/- 3 versus 44.4 +/- 4 mm Hg and 7.10 +/- 0.03 Versus 7.37 +/- 0.03, respectively. Followin g left lung ischemia and reperfusion, TH versus control was associated with preservation of lung mechanics, attenuation of protein leakage, reduction in pulmonary edema, and improved oxygenation. Indices of systemic protectio n included improved acid-base and lactate profile, in the absence of system ic hypoxemia. In the TH group, mean BALF TNF-alpha levels were 3.5% of CON levels (p < 0.01), and mean 8-isoprostane levels were 30% of CON levels (p = 0.02). Western blot analysis demonstrated reduced lung tissue nitrotyrosi ne in TH, indicating attenuation of tissue nitration. Finally, preliminary data suggest that TH may attenuate apoptosis following lung IR. We conclude that in the current model TH is protective versus IR lung injury and mecha nisms of protection include preservation of lung mechanics, attenuation of pulmonary inflammation, and reduction of free radical mediated injury. If t hese findings are confirmed in additional models, TH may become a candidate for clinical testing in critical care.