Isolated Lung Perfusion with Cisplatin in Rabbit - evaluation of pharmacokinetics and long term pathologic changes of the lung / 대한흉부외과학회지

ABSTRACT

BACKGROUND: Recently, regional or isolated organ perfusion is being studied again as a drug administration modality which is able to reduce systemic toxicity while delivering high-dose chemotherapeutic agents. This research was planned to evaluate the pharmacokinetics and long-term pathologic changes of the lung in isolated lung perfusion (ILP) with cisplatin. MATERIAL AND METHOD: Twenty-five New Zealand white rabbits were divided into 2 groups (Group I: 10, Group II: 15). The groups were then subdivided into 2 and 3 subgroups of 5 rabbits. In group I, tissue samples of the lung and kidney, and systemic blood for platinum concentration measurement were taken 30 minutes after systemic intravenous infusion of cisplatin (5 mg/kg) and isolated lung perfusion in each 5 rabbits. In 2 subgroups of group II, lung tissues for pathologic exams were taken 30 minutes and 1 week after ILP in each 5 rabbits, which received 10% pentastarch solution only and cisplatin, respectively. In the other subgroups, lung biopsy was undertaken 4 weeks after ILP with cisplatin. RESULT: When cisplatin was infused via systemic vein, the platinum concentration in the lung, kidney and plasma were 1.50+/-0.43 microgram/g, 7.65+/-2.49 microgram/g, 1.19+/-0.03 microgram/ml, respectively. However, the platinum concentration in the lung was about 50 times higher (75.43+/-11.47 microgram/g) than that of intravenous infusion group, and those in the kidney and plasma were decreased (1.30+/- 0.35 microgram/g, 0.13+/-0.02 microgram/ml) when cisplatin was introduced through ILP. Pathologic change in the treated lung with ILP was characterized by the medial hypertrophy of the pulmonary arterioles and interstitial eosinophilic infiltration, which was not dependent on cisplatin.