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J Thorac Cardiovasc Surg 1998;116:932-942
© 1998 Mosby, Inc.

CARDIOTHORACIC TRANSPLANTATION

RAPID REPERFUSION CAUSES STRESS FAILURE IN ISCHEMIC RAT LUNGS

Supported by the Ontario Thoracic Society and the Medical Research Council of Canada. Dr Pierre is a recipient of the Ortho/Biotech Research Fellowship from the International Society for Heart and Lung Transplantation. Dr Pierre and Dr DeCampos are recipients of fellowships from the Canadian Cystic Fibrosis Foundation.

Received for publication March 27, 1998. Revisions requested June 11, 1998; revisions received July 9, 1998. Accepted for publication July 15, 1998. Address for reprints: Shaf H. Keshavjee, MD, MSc, Division of Thoracic Surgery, The Toronto Hospital, 200 Elizabeth St, EN 10-224, Toronto, Ontario M5G 2C4, Canada.

Objective: Rapid reperfusion may be injurious to the ischemic lung. Our aim was to confirm that slow reperfusion improves postischemic pulmonary function and to elucidate the ultrastructural changes associated with slow versus rapid reperfusion.
Methods: We used an ex vivo perfused rat lung transplant model to study the effect of slow versus rapid reperfusion on subsequent lung function and morphologic condition. Functional assessment was performed in (1) fresh lung, slowly reperfused; (2) fresh lung, rapidly reperfused; (3) ischemic lung (4 hours at 22°C), slowly reperfused; and (4) ischemic lung, rapidly reperfused.
Results: In group 4, the shunt fraction (P = .001), airway pressure (P = .001), and wet/dry ratio (P = .01) were significantly higher than in groups 1 through 3. Light and electron microscopy of slowly reperfused ischemic lungs (n = 4) appeared normal. Rapidly reperfused ischemic lungs (n = 4) demonstrated massive alveolar edema, hemorrhage, and epithelial "blebbing" by light microscopy. Electron microscopy identified the blebbing as separation of the epithelial layer from an intact basement membrane by edema fluid. The epithelial layer was disrupted in numerous locations. Complete disruption of all layers of the blood-gas barrier was occasionally present.
Conclusion: Rapid reperfusion of the ischemic lung is an important contributing factor to reperfusion lung injury resulting in mechanical stress failure of the alveolar/capillary barrier. Gradual reintroduction of blood flow to the ischemic lung improves oxygenation.

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