Ischemia-reperfusion lung injury in rabbits: mechanisms of injury and protection

To study the mechanisms responsible for ischemia-reperfusion lung injury, w e developed an anesthetized rabbit model in which the effects of lung defla tion, lung inflation, alveolar gas composition, hypothermia, and neutrophil s on reperfusion pulmonary edema could be studied. Rabbits were anesthetize d and ventilated, and the left pulmonary hilum was clamped for either 2 or 4 h. Next, the left lung was reperfused and ventilated with 100% oxygen. As indexes of lung injury we measured arterial oxygenation, extravascular lun g water, and the influx of a vascular protein (I-131-labeled albumin) into the extravascular space of the lungs. The principal results were that I)all rabbits with the deflation of the lung during ischemia for 4 h died of ful minant pulmonary edema within 1 h Of reperfusion; 2) inflation of the ische mic lung with either 100% oxygen, air, or 100% nitrogen prevented the reper fusion lung injury; 3) hypothermia at 6-8 degrees C also prevented the repe rfusion lung injury; 4) although circulating neutrophils declined during re perfusion lung injury, there was no increase in interleukin-8 levels in the plasma or the pulmonary edema fluid, and, furthermore, neutrophil depletio n did not prevent the reperfusion injury; and 5) ultrastructural studies de monstrated injury to both the lung endothelium and the alveolar epithelium after reperfusion in deflated lungs, whereas the inflated lungs had no dete ctable injury. In summary, ischemia-reperfusion injury to the rabbit lung c an be prevented by either hypothermia or lung inflation with either air, ox ygen, or nitrogen.