Effects of induction therapy on wound healing at bronchial anastomosis sites in rats

Preoperative chemotherapy is frequently used for advanced lung cancer. As a valid alternative to pneumonectomy, bronchoplasty has the advantage of enabling lung parenchyma function to be preserved. The effects of antineoplastic agents on healing bronchial anastomosis remain unclear. We studied the effects of preoperative chemotherapy on wound healing in bronchial anastomoses and clarified causes of wound healing impairment in rats. In experiment I, at 3 days before surgery, rats were injected with cyclophosphamide, doxorubicin, and vincristine (CAV group) or cisplatin and etoposide (PVP treated rats). In experiment II, at 48 hrs before surgery, rats were treated with rabbit antirat macrophage serum and antirat monocyte chemoattractant protein-1 antibody to inhibit macrophage infiltration. On days 3, 5, and 7 after bronchus anastomosis, wound healing was assessed by examining bursting strength and hydroxyproline tissue content. CAV-treated rats showed significant impaired wound healing, marked severe leucopenia, and reduced macrophage infiltration. The PVP group showed no significant changes. In experiment II, rats exhibited inhibited macrophage infiltration, which is associated with significantly impaired of wound healing. Our study suggests that induction chemotherapy, associated with leukopenia in the early phase of wound healing, increases the risk of bronchial anastomosis leakage. Postoperative macrophage depletion is one of the most important causes of impaired wound healing.