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Ann Thorac Surg 1993;56:209-214
© 1993 The Society of Thoracic Surgeons
Thoracic Oncology/Surgical Metabolism Laboratory, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York USA
* Address reprint requests to Dr Burt, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.
To investigate new modalities in the treatment of pulmonary metastases we developed a model of isolated singlelung perfusion in the rat. In this study we compare the pharmacokinetics of isolated lung perfusion and intravenous doxorubicin. In the first experiment, designed to evaluate lung tissue levels of doxorubicin, 35 rats were randomized into seven groups (n = 5). The first five groups underwent isolated lung perfusion with 72.1 ± 6.9, 118.4 ± 12.1, 255.2 ± 12.8, 384.1 ± 46.2, and 457.6 ± 32.5 µg/mL of doxorubicin, respectively, for 10 minutes. Groups 6 and 7 received 5 mg/kg and 7 mg/kg of intravenous doxorubicin, respectively. A second study was designed to measure heart tissue level of doxorubicin in 3 groups of 5 rats each. Two groups received 5 or 7 mg/kg of intravenous doxorubicin and a third group underwent isolated lung perfusion with 255.2 ± 12.8 µg/mL of doxorubicin for 10 minutes. A third study, designed to evaluate toxicity in vivo, had a similar design, and the animals were followed up for 21 days after treatment. Lung doxorubicin concentration after isolated lung perfusion was significantly higher than after intravenous doxorubicin (p < 0.01). Tissue doxorubicin concentration was 25 and 20 times higher after isolated lung perfusion with 255.2 ± 12.8 µg/mL than after 5 or 7 mg/kg of intravenous doxorubicin, respectively. Heart concentration of doxorubicin was significantly lower after isolated lung perfusion with 255.2 ± 12.8 µg/mL of doxorubicin as compared with 5 or 7 mg/kg of intravenous doxorubicin (p < 0.001). Animals that had systemic intravenous doxorubicin failed to gain weight as compared with animals after isolated lung perfusion (p < 0.006). In conclusion, isolated lung perfusion with doxorubicin is pharmacokinetically superior to systemic intravenous doxorubicin in this model.
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