Single-pass isolated lung perfusion versus recirculating isolated lung perfusion with melphalan in a rat model.
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 x 10(6) 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 degrees C to 37 degrees 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.
Van Putte
Bart P
BP
Department of Thoracic and Vascular Surgery, University of Antwerp, Belgium.
Hendriks
Jeroen M H
JM
Romijn
Sander
S
Guetens
Gunther
G
De Boeck
Gert
G
De Bruijn
Ernst A
EA
Van Schil
Paul E Y
PE
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary*; D000818:Animals; D001682:Biological Availability; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000295:instrumentation*; D003110:Colonic Neoplasms / Q000473:pathology*; D007261:Infusions, Intra-Arterial / Q000295:instrumentation*; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D008297:Male; D008558:Melphalan / Q000493:pharmacokinetics / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D008558:Melphalan