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Ann Thorac Surg 2002;74:893-898
© 2002 The Society of Thoracic Surgeons

Original article: general thoracic

Single-pass isolated lung perfusion versus recirculating isolated lung perfusion with melphalan in a rat model

Bart P. Van Putte, MDa, Jeroen M.H. Hendriks, MD, PhDa, Sander Romijn, MDa, Gunther Guetens, PhDb, Gert De Boeck, PhDb, Ernst A. De Bruijn, PharmDb, Paul E.Y. Van Schil, MD, PhD*a

a Department of Thoracic and Vascular Surgery, University of Antwerp, Antwerp, Belgium
b Department of Oncology and Radiotherapy, Catholic University of Leuven, Leuven, Belgium

* Address reprint requests to Dr Van Schil, MD, Department of Thoracic and Vascular Surgery, University Hospital Antwerp (UZA), Wilrijkstraat 10, B-2650 Edegem, Belgium
e-mail: paul.van.schil{at}uza.be

Presented at the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Launderdale, FL, Jan 28–30, 2002.

Background. Isolated lung perfusion (ILuP) with melphalan (MN) is superior to intravenous infusion for the treatment of pulmonary carcinoma and sarcoma metastases. However, it is unknown whether a bolus injection of MN into the perfusion circuit or ILuP with a fixed concentration of MN will result in the highest lung levels.

Methods. ILuP with 0.5 mg MN was performed in Wag- Rij rats for 30 minutes either by a single-pass system (SP) (fixed concentration) (n = 10) or by reperfusion (RP) (bolus injection) (n = 10). In a separate experiment, rats were perfused with blood as the perfusate. In a third experiment, tumor levels were compared between SP, RP, or intravenous therapy with a dose of 0.5 mg. For induction of pulmonary metastases, 0.5 x106 single adenocarcinoma cells were injected intravenously and therapy was given on day 30. For comparison of drug concentrations, unpaired Student’s t test was applied. Statistical significance was accepted at p less than 0.05.

Results. Lung perfusion studies were succesfully performed without systemic leakage. Temperature of perfusate and rats was 34°C to 37°C. A significantly higher hematocrit (mean 27.9) compared with buffered starch (mean 2.5) did not result in higher MN lung levels or lower wet-to-dry ratio. Tumor levels were significantly higher after ILuP compared with intravenous therapy. However, no difference in tumor and lung levels was seen between single-pass and reperfusion.

Conclusions. Both ILuP techniques resulted in significantly higher MN lung levels than after intravenous therapy. Because no difference was seen between single-pass and recirculating perfusion, MN can be injected as a bolus into the closed perfusion circuit.




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