Original article
Improved tracheal allograft viability in immunosuppressed rats

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Abstract

Airway ischemia has been a common cause of morbidity and mortality in clinical lung transplantation. The present study examined the effects of cyclosporin A (CsA) and methylprednisolone (MP) on the viability of the devascularized trachea after heterotopic transplantation and omentopexy. Thirty-six tracheal segments were harvested from 18 donor Lewis rats, wrapped in omentum, and heterotopically implanted into the abdomen of recipient rats. Tracheal segments were randomly allocated into one of six recipient groups (n = 6): Lewis syngeneic controls, and five groups of Brown Norway recipients, receiving either no treatment, CsA alone (5 mg · kg−1 · day−1 or 15 mg · kg−1 · day−1), or CsA in combination with MP (5 mg CsA + 1 mg MP per kg/day or 15 mg CsA + 2 mg MP per kg/day, respectively). After 14 days, the tracheal segments were histologically evaluated. Epithelial thickness and the degree of epithelial regeneration were significantly different (p < 0.05) between the syngeneic control group and the untreated Brown Norway group. Without immunosuppression there was virtually no epithelium, whereas low-dose immunosuppression yielded intermediate viability, and with high dose CsA and MP we observed improved tracheal viability. In this high-dose group, the epithelium was thicker than in even the syngeneic control group. These results indicate that, in heterotopic tracheal allografts, viability may be improved with an optimum combination of CsA and MP.

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Cited by (24)

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    Some studies have examined the effects of CsA on the severity of rejection in transplant recipients. Davreux et al. examined the effect of CsA in a heterotopic tracheal allotransplantation model and showed dose-dependent preservation of the epithelium when tracheal segments were examined at day 14 [17]. In the current study, to evaluate the progress of the severity of chronic rejection, a sub-optimal dose of CsA was administered to prolong allograft rejection instead of an optimal dose.

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  • Minimal dose of cyclosporin A for tracheal allografts

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Supported by The Canadian Cystic Fibrosis Foundation.

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