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Am J Physiol Lung Cell Mol Physiol 276: L137-L145, 1999;
1040-0605/99 $5.00
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Vol. 276, Issue 1, L137-L145, January 1999

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

Tsutomu Sakuma, Keiji Takahashi, Nobuo Ohya, Osamu Kajikawa, Thomas R. Martin, Kurt H. Albertine
Michael A. Matthay
(With the Technical Assistance of Oscar O. Osorio)

Department of Respiratory Medicine, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan; Cardiovascular Research Institute, University of California, San Francisco, California 93143; Department of Veterans Affairs Medical Center, Seattle, Washington 98108; and Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132

To study the mechanisms responsible for ischemia-reperfusion lung injury, we developed an anesthetized rabbit model in which the effects of lung deflation, lung inflation, alveolar gas composition, hypothermia, and neutrophils on reperfusion pulmonary edema could be studied. Rabbits were anesthetized 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 lung water, and the influx of a vascular protein (131I-labeled albumin) into the extravascular space of the lungs. The principal results were that 1) all rabbits with the deflation of the lung during ischemia for 4 h died of fulminant pulmonary edema within 1 h of reperfusion; 2) inflation of the ischemic lung with either 100% oxygen, air, or 100% nitrogen prevented the reperfusion lung injury; 3) hypothermia at 6-8°C also prevented the reperfusion lung injury; 4) although circulating neutrophils declined during reperfusion lung injury, there was no increase in interleukin-8 levels in the plasma or the pulmonary edema fluid, and, furthermore, neutrophil depletion did not prevent the reperfusion injury; and 5) ultrastructural studies demonstrated injury to both the lung endothelium and the alveolar epithelium after reperfusion in deflated lungs, whereas the inflated lungs had no detectable injury. In summary, ischemia-reperfusion injury to the rabbit lung can be prevented by either hypothermia or lung inflation with either air, oxygen, or nitrogen.

lung transplantation; pulmonary edema; hypoxia; hypothermia; neutrophil


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