ISCHEMIA-REPERFUSION LUNG INJURY ATTENUATED BY ATP-MGCL2 IN RATS

The protective effect of ATP-MgCl2 on ischemia-reperfusion lung injury has been reported in kidney, liver, heart, and muscle but has not bee n examined in lungs. The aim of this study was to determine whether AT P or ATP-MgCl2 pretreatment would attenuate ischemia-reperfusion-induc ed acute lung injury and to identify the possible mechanisms for such protection. Typical acute lung injury was successfully induced in Spra gue-Dawley rats by 10 min of hypoxia followed by 75 min of ischemia an d 50 min of reperfusion. Pretreatment with ATP-MgCl2 (or adenosine) bu t not ATP or MgCl2 (all at 10(-6) M) significantly attenuated the acut e lung injury. All the protective effects of ATP-MgCl2 were nearly und etectable when promazine (an ecto-adenosinetriphosphatase inhibitor) o r 3,7-dimethyl-1-propargylxanthine (an A(2)-receptor antagonist) was a dded before ATP-MgCl2 pretreatment. These observations support our hyp othesis that the protective effect of ATP-MgCl2 is in part mediated th rough adenosine, the degradation product of ATP, which is produced by the Mg2+-dependent ecto-adenosinetriphosphatase on the surface of neut rophils and reacts with neutrophil A(2) receptors to inhibit the produ ction of O-2 radicals.