EFFECT OF METHYLPREDNISOLONE ON ANGIOGENESIS IN SYNGENEIC RAT TRACHEAL GRAFTS

Airway anastomotic complications remain a cause of morbidity after cli nical lung transplantation. The use of corticosteroid therapy to contr ol pulmonary rejection has raised concern over delayed airway healing. We therefore investigated the hypothesis that the effects of methylpr ednisolone (MP) impair the revascularization and epithelial regenerati on of heterotopic syngeneic tracheal isografts. Lewis rat tracheal seg ments were wrapped in omentum and implanted in the abdomen of recipien t rats. All recipients received cyclosporin A (CsA) (5 mg.kg(-1).day(- 1)) and were randomly allocated into three groups of 12 rats each acco rding to the daily MP dose: group II, no MP; group III, 1 mg.kg(-1).da y(-1); and group IV, 2 mg.kg(-1).day(-1). In each group, 6 animals wer e sacrificed after 7 and 14 days. Normal, untreated rats served as con trols (group I). Epithelial regeneration was assessed histologically b y a blinded subjective scoring system and by measurement of epithelial thickness. Tracheal revascularization was quantitated in terms of the number of blood vessels per square millimeter of tracheal wall and th e vessel area was quantitated in terms of the percentage of the trache al wall area. In animals treated with MP and CsA, the trachea exhibite d significantly better regeneration after 14 days than it did in anima ls treated only with CsA. Epithelial regeneration was improved between 7 and 14 days in the groups treated with MP (group III, p = 0.01; gro up IV, p = 0.04). The epithelial thickness for all three study groups was significantly greater than that in the control group and returned toward normal after 14 days. The epithelium was significantly thinner in groups III and IV after 14 days than it was in group II after 7 day s (p < 0.05). There were no significant differences among the groups i n terms of revascularization at any time. We conclude that, in the set ting of heterotopic rat tracheal isografts treated with CsA, angiogene sis is not inhibited and epithelial regeneration is accelerated by MP treatment.