Remote reperfusion lung injury is associated with AMP deaminase 3 activation and attenuated by inosine monophosphate.

BACKGROUND Remote reperfusion lung injury occurs in patients with vascular occlusion and surgical procedures. Inosine monophosphate (IMP) produced by adenosine monophosphate deaminase (AMPD) 3 is involved in the remote reperfusion injury. The purpose of the present study was to identify whether IMP administration attenuated the remote reperfusion lung injury in a skeletal muscle ischemia-reperfusion model. METHODS AND RESULTS A remote reperfusion lung injury was created using reperfusion after the bilateral ligation of the hind-limb. AMPD activity, myeloperoxidase (MPO) activity, IMP, AMPD3 mRNA and tumor necrosis factor (TNF)-alpha in the lungs before and after reperfusion were analyzed. Furthermore, the effects of IMP on these parameters were examined. AMPD3 mRNA, AMPD activity and IMP production in the lungs significantly increased after ischemia-reperfusion with increases in MPO activity, TNF-alpha level and decreased oxygen saturation (SpO(2)). Histological examination of the lungs demonstrated significant neutrophil infiltration and accumulation. IMP administration significantly reduced MPO activity, TNF-alpha and neutrophil infiltration, with ameliorated SpO(2). CONCLUSIONS Along with the activation of AMPD3, ischemia-reperfusion-induced lung inflammation is associated with increased MPO activity and TNF-alpha level. IMP significantly decreased the lung injury, MPO activity, TNF-alpha and increased SpO(2). These findings may lead to the development of a new therapeutic strategy for remote reperfusion lung injury.