Vancomycin lung concentration in acute and hyperacute rejection models of lung transplantation in rats.
OBJECTIVE
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.
Department of General Thoracic Surgery, Pomeranian Medical University, Szczecin, Poland.
Jarosław
J
Pieróg
Bartosz
B
Kubisa
Marek
M
Droździk
Janusz
J
Wójcik
Michał
M
Bielewicz
Juliusz
J
Pankowski
Krzysztof
K
Safranow
Tomasz
T
Grodzki
D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D016040:Lung Transplantation; D008297:Male; D009894:Opportunistic Infections / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D014640:Vancomycin