The protective effect of acadesine on lung ischemia-reperfusion injury.
The purine precursor acadesine is highly effective in preventing ischemia-reperfusion (I-R) injury of the heart and intestine. The aim of this study was to test the effect of acadesine on I-R--induced lung injury. The lobar artery of the left lower lung lobe in intact-chest, spontaneously breathing cats was occluded for 2 h (Group 1, ischemia) and reperfused for 3 h (Group 2, I-R). Animals were subjected to one of the following three protocols: acadesine administered IV 15 min before ischemia (Group 3), 15 min before reperfusion (Group 4), or 30 min after reperfusion (Group 5). Acadesine was administered at an initial dose of 2.5 mg. kg(-1). min(-1) for 5 min, followed by 0.5 mg. kg(-1). min(-1) until the end of reperfusion. Injury was assessed by histologic examination. The right lower lobe served as control. Compared with the right lower lobe, which showed no abnormal findings in any group (percentage of injured alveoli, 2% +/- 1% to 4% +/- 2%), the left lower lung lobe in the I-R group revealed a disrupted alveolar structure with 63% +/- 9% injured alveoli. Ischemia alone did not produce alterations in alveolar structure. Acadesine significantly reduced the number of injured alveoli when given before ischemia (4% +/- 1%) or reperfusion (6% +/- 2%) but not when administered after reperfusion (62% +/- 8%). In conclusion, acadesine, when administered before ischemia or reperfusion, can blunt I-R-induced lung injury. The mechanism underlying the protection remains to be elucidated.


CONCLUSIONS
Acadesine reduces ischemia-reperfusion-induced lung injury in spontaneously breathing cats when administered before ischemia or reperfusion, but not after reperfusion.
Department of Anesthesiology and CCM, Hadassah University Medical Center, The Hebrew University of Jerusalem, Israel. matoth@cc.huji.ac.il
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D007511:Ischemia / Q000188:drug therapy*; D008168:Lung / Q000098:blood supply*; D015427:Reperfusion Injury / Q000517:prevention & control*; D012263:Ribonucleosides / Q000494:pharmacology*
D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D000255:Adenosine Triphosphate