Vancomycin lung concentration in acute and hyperacute rejection models of lung transplantation in rats.

Abstract

OBJECTIVES: This study assesses vancomycin concentrations in allogenic transplanted rat lung tissue in acute and hyperacute rejection models of the lung. METHODS: Left lung allotransplantation was performed from a male Brown Norway donor to a male Fisher F344 recipient in the case of an acute rejection model (the animals were sacrificed 5 days after transplantation) as well as a male Brown Norway donor to a male Wistar recipient in the case of hyperacute rejection (the animals were sacrificed 2 days after transplantation). Control rats were sham-operated and sacrificed on day 2 or 5, respectively, of the experimental model. Rejection was confirmed by blood gas assessment and lung histological examination. A single intraperitoneal dose of vancomycin 30 mg kg(-1) body weight was administered on the day of autopsy (day 2 or 5 from transplantation, respectively, of the experimental model), and then the blood and lung specimens were sampled at 0, 5, 1, 2, 4 and 6h from the time of drug injection. RESULTS: Arterial blood gas assessment (Wistar rats - pO(2): 44.33 ± 21.73 mmHg (mean ± standard deviation (SD)); Fisher rats - pO(2:) 50.67 ± 14.30 mmHg (mean ± SD)) as well as histopathologic examinations of lung grafts confirmed rejection. Vancomycin lung/plasma concentration ratio was significantly higher in transplanted rats than in sham-operated animals. CONCLUSIONS: Both acute and hyperacute lung rejection affect the lung/serum of vancomycin in the transplanted lung resulting in higher drug accumulation, especially in late post-dosage time.