Original article: general thoracic
Single-pass isolated lung perfusion versus recirculating isolated lung perfusion with melphalan in a rat model

Presented at the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Launderdale, FL, Jan 28–30, 2002.
https://doi.org/10.1016/S0003-4975(02)03802-XGet rights and content

Abstract

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 ×106 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.

Section snippets

Animals

Male inbred WAG-Rij strain rats (approximately 200 g), obtained from Harlan-CPB (Zeist, The Netherlands), were used for all experiments. Animals were treated in accordance with the Animal Welfare Act and the “Guide for the Care and Use of Labaratory Animals” (National Institutes of Health Publication 86 to 23, revised 1985). The rats were transported in sterile conditions, housed in suspended mesh wired cages, and ad libitum fed a standard pellet diet (standard rat chow; Hope Farms, Woerden,

Mortality

All rats survived injection of tumor cells, and the procedure-related survival was 100% for all experiments.

Experiment 1

The temperature of the reservoir and the rats was not significantly different between groups (Table 1). Hematocrit levels were significantly lower for groups 1 and 2 (BHE perfusate) compared with groups 3 and 4 (RBC-BHE perfusate). No significant difference was seen in wet-to-dry ratios between the groups (Table 1).

No significant difference was seen in the left lung MN levels of rats

Comment

Whereas the lungs are the most common site of metastases [14], it is known that for sarcoma and carcinoma metastases, up to 50% of the patients have recurrent disease exclusively in the lung after resection of the primary disease, probably due to the presence of micrometastases at the time of the initial operation 1, 15. Recurrent disease can be inoperable due to size, number, or location of these lung metastases. Therefore, it is important to have local control of microscopic disease after

Acknowledgements

This work was supported by a research grant from the University of Antwerp.

References (25)

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