An Experimental Study of Isolated Lung Perfusion with TNF-alpha and DXR as The Treatment of Metastatic Lung Tumor

• Project/Area Number: 07671490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kansai Medical University
• Principal Investigator: SAITOH Yukihito Kansai, Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50131438)
• Co-Investigator(Kenkyū-buntansha): UMEMOTO Masao Kansai, Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60148509)
• Project Period (FY): 1995 – 1996
• Project Status: Completed (Fiscal Year 1996)
• Budget Amount: ¥1,800,000 (Direct Cost: ¥1,800,000); Fiscal Year 1996: ¥300,000 (Direct Cost: ¥300,000); Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: metastatic lung tumor / isolated lung perfusion / pulmonary artery perfusion with blood flow occlusion / cisplatin (CDDP) / 5-fluorouracil (5-FU) / mitomycin C (MMC) / 一側肺灌流(isolated lung perfusion) / pulmonary artery perfusion with blood flow ocelusion / cisplatin(CDDP) / ラット結腸癌肺転移 / TNF-α / 一側肺還流 / DXR

Research Abstract

Purpose : Recently metastatic lung diseases have been increasing. In this study, we evaluated the pharmacokinetics of isolated lung perfusion (ILP) and pulmonary artery perfusion with blood flow occlusion (PA) to establish more effective treatment for metastatic lung diseases.
Methods : In male F344 rats, left ILP and PA were performed with cisplatin (CDDP), 5-fluorouracil (5-FU), mitomycin C (MMC), then the levels of the agents in the left lung and serum were measured, and the results were compared with those of intravenous administration. In ILP groups, left pulmonary artery and vein were clamped. Perfusion was performed with the agents from the pulmonary artery at the flow rate of 0.5ml/min for 10 minutes, then flush with saline was done for 5 minutes. After the suturing of the vessels, clamps were removed. In PA roups, left pulmonary artery was clamped and perfused the agents at the floe rate of 0.2ml/min for 1 minute, and pulmonary artery flow was occluded. After 20 minutes of occlusion, pulmonary artery was declamped. Both groups, the left lung and blood were corrected after 5 minutes of declamp.
Results : The lung and serum CDDP levels were 13.1(]SY.+-。[)2.5 mug/g and 0.2(]SY.+-。[)0.05 mug/ml in 0.2mg/ml ILP,9.5(]SY.+-。[)1.7mug/g and 0.2(]SY.+-。[)0.05 mug/ml in 0.5mg/kg PA,and 1.4(]SY.+-。[)0.08 mug/g and 1.0(]SY.+-。[)0.2 mug/ml in 2 mg/kg IV.The lung and serum 5-FU levels were 1585(]SY.+-。[)431.5 mug/g and 66.5(]SY.+-。[)15.8 mug/ml in 20mg/ml ILP,2282.5(]SY.+-。[)413.4 mug/g and 15.6(]SY.+-。[)3.4 mug/ml in 50mg/kg PA,and 26.1(]SY.+-。[)0.7 mug/g and 33.9(]SY.+-。[)0.2 mug/ml in 30mg/kg IV.Finally, The lung and serum MMC levels were 287.0(]SY.+-。[)148.6 ng/g and 9.4(]SY.+-。[)1.2 ng/ml in 0.03mg/ml ILP,383.5(]SY.+-。[)99.2 ng/g and 8.4(]SY.+-。[)3.2 ng/ml in 0.05mg/kg PA,and 212(]SY.+-。[)28.8 ng/g and 176.5(]SY.+-。[)18.0 ng/ml in 0.5mg/kg/day IV*7days.
Conclusion : ILP and PA can provide higher levels of the chemotherapeutic agents with lower systemic toxicity.