Abstract
group received a 28-day course of ZVAD-fmk (1 mg/kg/day) via subcutaneous mini-osmotic pumps, starting at the time of transplantation. For the apoptosis time course, allografts were harvested on post-op days 1, 3, 4, 7, 14, 21 and 28. Fas knockout and ZVAD-treated allografts were harvested on day 28. Histological, morphometric and in-situ TUNEL analyses were performed in a blinded fashion. Results: From days 1-7, allograft airway epithelial cells appear to be undergoing apoptosis. On day 28, the mean airway obliteration in both the Fas knockout group (65.63% /20.90 (mean /S.D.), p 0.004) and the ZVAD group (70.83% /14.71, p 0.011) were significantly reduced compared to controls (97.92% /4.07 and 98.98% /0.82, respectively). The airway epithelium was not preserved in Fas knockout allografts or controls. Conclusion: While apoptosis of airway epithelial cells does occur in the setting of allograft airway transplantation, inhibition of apoptosis, through broad-spectrum caspase inhibition or Fas pathway blockade, only partially prevents airway obliteration.
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