Hypercapnic acidosis attenuates reperfusion injury in isolated and perfused rat lungs

Although ischemia-reperfusion injury is a major determinant of primary graft dysfunction after lung transplantation, an approach to extend preoperative lung preservation to postoperative protection has not yet been defined. The purpose of this study was to determine the protective effects of and the signal pathway regulated by hypercapnic acidosis in ischemia-reperfusion-induced lung injury.

Animal study.

Animal care facility procedure room in a medical center.

Adult male Sprague-Dawley rats.

Lung injury was induced in a clinically relevant ex vivo animal model. Animals were divided into a control group (FICO(2), 5%; n = 6), ischemia-reperfusion group (FICO(2), 5%; n = 6), and hypercapnic acidosis (ischemia-reperfusion + hypercapnic acidosis) group (FICO(2), 10%; n = 6).

Ischemia-reperfusion caused significant increases in alveolar lavage and perfusate tumor necrosis factor-α, inflammatory cell infiltration, lung tissue malondialdehyde, bronchoalveolar lavage fluid protein concentration and lactate dehydrogenase activity, lung weight gain, and infiltration coefficient. Ventilation with 10% CO(2) significantly suppressed the inflammatory response and attenuated lung ischemia-reperfusion injury. Our results also showed that hypercapnic acidosis significantly inhibited the ischemia-reperfusion-induced phosphorylation and nuclear translocation of nuclear factor-κB. This was associated with elevation of inhibitor of nuclear factor-κB-α level and reduced IκB kinase-β phosphorylation, suggesting a suppression of IκB kinase and thus IκB-α activation.

Hypercapnic acidosis may attenuate lung ischemia-reperfusion injury by suppressing the activation of the IκB kinase-nuclear factor-κB pathway.