Inhalation of carbon monoxide reduces skeletal muscle injury after hind limb ischemia-reperfusion injury in mice

Background: The purpose of this study was to determine if inhaled carbon monoxide (CO) can ameliorate skeletal muscle injury, modulate endogenous heme oxygenase-1 expression, and improve indexes of tissue integrity and inflammation after hind limb ischemia reperfusion. Methods: C57BL6 mice inhaling CO (250 ppm) or room air were subjected to 1.5 hours of ischemia followed by limb reperfusion for either 3 or 6 hours (total treatment time, 4.5 or 7.5 h). After the initial period of reperfusion, all mice breathed only room air until 24 hours after the onset of ischemia. Mice were killed at either the end of CO treatment or at 24 hours' reperfusion. Skeletal muscle was subjected to histologic and biochemical analysis. Results: CO treatment for 7.5 hours protected skeletal muscle from histologic and structural evidence of skeletal muscle injury. Serum and tissue cytokines were reduced significantly (P <.05) in mice treated with CO for 7.5 hours. Tubulin, heme oxygenase, and adenosine triphosphate levels were higher in CO-treated mice. Conclusions: Inhaled CO protected muscle from structural injury and energy depletion after ischemia reperfusion.