Remote Reperfusion Lung Injury is Associated With AMP Deaminase 3 Activation and Attenuated by Inosine Monophosphate

• Published in: Circulation Journal 2007, Vol.71(4), pp.591-596
• Main Authors: Li, Peili, Ogino, Kazuhide, Hoshikawa, Yoshiko, Morisaki, Hiroko, Cheng, Jidong, Toyama, Keiko, Morisaki, Takayuki, Hashimoto, Kiyoshi, Ninomiya, Haruaki, Tomikura-Shimoyama, Yoko, Igawa, Osamu, Shigemasa, Chiaki, Hisatome, Ichiro
• Format: Article
• Language: English
• Subjects: AMP deaminase; AMP Deaminase - genetics; AMP Deaminase - physiology; Animals; Disease Models, Animal; Enzyme Activation; Gene Expression Regulation, Enzymologic; IMP; Inosine Monophosphate - genetics; Inosine Monophosphate - physiology; Inosine Monophosphate - therapeutic use; Lung - enzymology; Lung - pathology; Lung Injury; Male; Mice; Mice, Inbred BALB C; Muscle, Skeletal - enzymology; Neutrophil; Peroxidase - metabolism; Peroxidase - physiology; Remote reperfusion injury; Reperfusion Injury - drug therapy; Reperfusion Injury - enzymology; RNA, Messenger - genetics; RNA, Messenger - metabolism; TNF-α; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.71.591

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)-α 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-α level and decreased oxygen saturation (SpO2). Histological examination of the lungs demonstrated significant neutrophil infiltration and accumulation. IMP administration significantly reduced MPO activity, TNF-α and neutrophil infiltration, with ameliorated SpO2. Conclusions Along with the activation of AMPD3, ischemia-reperfusion-induced lung inflammation is associated with increased MPO activity and TNF-α level. IMP significantly decreased the lung injury, MPO activity, TNF-α and increased SpO2. These findings may lead to the development of a new therapeutic strategy for remote reperfusion lung injury. (Circ J 2007; 71: 591 - 596)