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J Thorac Cardiovasc Surg 2006;132:304-311
© 2006 The American Association for Thoracic Surgery

General Thoracic Surgery

Cytostatic lung perfusion results in heterogeneous spatial regional blood flow and drug distribution: Evaluation of different cytostatic lung perfusion techniques in a porcine model

Thorsten Krueger, MD a , Andrea Kuemmerle, PhD b , Marek Kosinski, PhD c , Alban Denys, MD d , Lennard Magnusson, MD e , Roger Stupp, MD f , Angelika Bischof Delaloye, MD c , Walter Klepetko, MD g , Laurent Decosterd, PhD b , Hans-Beat Ris, MD a , * , Michael Dusmet, MD a

a Department of Thoracic Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
b Department of Clinical Pharmacology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
c Department of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
d Department of Radiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
e Department of Anesthesiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
f Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
g Department of Cardiothoracic Surgery, University Hospital of Vienna, Austria

Received for publication October 12, 2005; accepted for publication December 30, 2005.

* Address for reprints: Hans-Beat Ris, MD, Department of Thoracic Surgery University Hospital of Lausanne CH 1011 Lausanne, Switzerland. (Email: Hans-Beat.Ris{at}chuv.hospvd.ch).

OBJECTIVES: Comparison of doxorubicin uptake, leakage and spatial regional blood flow, and drug distribution was made for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), as opposed to intravenous administration in a porcine model.

METHODS: White pigs underwent single-pass lung perfusion with doxorubicin (320 µg/mL), labeled 99mTc-microspheres, and Indian ink. Visual assessment of the ink distribution and perfusion scintigraphy of the perfused lung was performed. 99mTc activity and doxorubicin levels were measured by gamma counting and high-performance liquid chromatography on 15 tissue samples from each perfused lung at predetermined localizations.

RESULTS: Overall doxorubicin uptake in the perfused lung was significantly higher (P = .001) and the plasma concentration was significantly lower (P < .0001) after all isolated lung perfusion techniques, compared with intravenous administration, without differences between them. Pulmonary artery infusion (blood flow occlusion) showed an equally high doxorubicin uptake in the perfused lung but a higher systemic leakage than surgical isolated lung perfusion (P < .0001). The geometric coefficients of variation of the doxorubicin lung tissue levels were 175%, 279%, 226%, and 151% for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), respectively, compared with 51% for intravenous administration (P = .09). 99mTc activity measurements of the samples paralleled the doxorubicin level measurements, indicating a trend to a more heterogeneous spatial regional blood flow and drug distribution after isolated lung perfusion and blood flow occlusion compared with intravenous administration.

CONCLUSIONS: Cytostatic lung perfusion results in a high overall doxorubicin uptake, which is, however, heterogeneously distributed within the perfused lung.

Abbreviations and Acronyms a-ILP = antegrade isolated lung perfusion; BFO = blood flow occlusion; c-ILP = combined antegrade and retrograde isolated lung perfusion; IV = intravenous; ln = natural logarithm; r-ILP = retrograde isolated lung perfusion




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