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Ann Thorac Surg 2006;82:2024-2030
© 2006 The Society of Thoracic Surgeons

Original Articles: General Thoracic

Antegrade Versus Retrograde Isolated Lung Perfusion: Doxorubicin Uptake and Distribution in a Sarcoma Model

Thorsten Krueger, MDa,*, Andrea Kuemmerle, PhDb, Snezana Andrejevic-Blant, MDc, Hua Yan, MDa, Youmin Pan, MDa, Jean-Pierre Ballini, PhDd, Walter Klepetko, MDe, Laurent Arthur Decosterd, PhDb, Roger Stupp, MDb, Hans-Beat Ris, MDa

a Division of Thoracic Surgery, Multidisciplinary Oncology Center, University Hospital, Lausanne, Switzerland
b Division of Clinical Pharmacology and Toxicology, Multidisciplinary Oncology Center, University Hospital, Lausanne, Switzerland
c Institute of Pathology, Multidisciplinary Oncology Center, University Hospital, Lausanne, Switzerland
d Air and Soil Pollution Laboratory, Swiss Federal Institute of Technology, Lausanne, Switzerland
e Department of Cardiothoracic Surgery, University Hospital, Vienna, Austria

Accepted for publication May 11, 2006.

* Address correspondence to Dr Krueger, Service de Chirurgie Thoracique et Vasculaire, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, CH 1011 Lausanne, Switzerland (Email: thorsten.krueger{at}chuv.ch).

BACKGROUND: Antegrade and retrograde doxorubicin-based isolated lung perfusions were compared in rodents bearing a sarcomatous tumor in the perfused lung. Inasmuch as these tumors derive their vascularization from the bronchial artery system, we hypothesized that retrograde isolated lung perfusion through the pulmonary vein might result in an improved tumor drug uptake.

METHODS: Single-pass antegrade (n = 9) and retrograde (n = 9) isolated left lung perfusions were performed with 100 µg of doxorubicin in Fischer rats 10 days after subpleural tumor cell injection. The perfusion, washout, and recirculation times were 20, 10, and 60 minutes, respectively, followed by harvesting of the lung. The doxorubicin concentration and compartmental distribution in the tumor and in normal parenchyma of each perfused lung were measured by high-pressure liquid chromatography (6 animals of each group) and fluorescence microscopy (3 animals of each group).

RESULTS: Doxorubicin concentration and pattern of doxorubicin-based fluorescence signaling were comparable for both perfusion techniques in normal lung tissue. Antegrade and retrograde isolated lung perfusion resulted in similar tumor drug uptake, which was lower than in normal lung parenchyma, and in weak and sporadic fluorescence signaling emerging from the tumor periphery and from blood vessels situated within the tumor tissue.

CONCLUSIONS: Retrograde isolated lung perfusion did not confer a better doxorubicin uptake in the tumor as compared with antegrade lung perfusion despite the fact that the tumor vascularization in this model is based on the bronchial artery circulation.


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