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297 ISCHEMIA-REPERFUSION INJURY IS INCREASED IN ETHANOL-FED DONOR RATS FOLLOWING 2 HOURS OF ISCHEMIA IN AN ISOLATED PERFUSED LUNG MODEL.
  1. C. D. Kershaw,
  2. R. C. Garcia,
  3. D. M. Guidot
  1. Atlanta VAMC and Emory University, Atlanta, GA

Abstract

Primary graft failure following lung transplantation bears considerable resemblance to the acute respiratory distress syndrome. There is leakage of inflammatory cells and proteinaceous fluid into the alveolar airspace, leading to hypoxemia, respiratory failure, and death in as many as 50% of cases. Despite improvements in allograft identification, procurement, and preservation, the incidence of primary graft failure following lung transplantation is 15 to 20%. Central to the pathogenesis of primary graft failure is alveolar epithelial cell dysfunction, a phenomenon also seen in alcoholics. Previously, we have shown that chronic ethanol ingestion produces oxidative stress and a disrupted alveolar epithelial barrier, rendering the lung susceptible to acute edematous during endotoxemia. In parallel, many organ donors are otherwise young healthy individuals with significant alcohol abuse histories who die in alcohol-related accidents. In order to test whether donor lungs from individuals who abuse alcohol could be more susceptible to ischemia-reperfusion injury and thus primary graft failure, we employed an isolated perfused rat lung model in endotoxemic, ethanol-fed versus control-fed rats. The lungs were isolated 2 hours after systemic administration of endotoxin (2 mg/kg of S. typhimurium lipopolysaccharide given intraperitoneally), which mimics the systemic inflammatory response syndrome observed in most lung allograft donors clinically. The isolated lungs were flushed and then preserved in Perfadex solution (a low potassium-dextran solution that is used to preserve human lung lung allografts prior to transplantation) and subjected to 2 hours of cold ischemia (48C). The preserved lungs were then reperfused for 45 minutes with Earle's balanced salt solution at 378C, after which lung tissue wet/dry ratios were determined (as an index of edematous injury). Isolated lungs from ethanol-fed rats had significantly more (p < .05) lung injury (Åtwice as much acute edema) as lungs from control-fed rats following cold ischemia and warm reperfusion. We conclude that chronic ethanol ingestion renders the lung more susceptible to ischemia-reperfusion injury in a model of primary graft failure. These findings suggest that lung allografts from alcoholic donors could be more susceptible to ischemia-reperfusion injury and may render the recipient at increased risk for primary graft failure and perhaps other forms of allograft dysfunction following lung transplantation.

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