Cytostatic lung perfusion results in heterogeneous spatial regional blood flow and drug distribution: evaluation of different cytostatic lung perfusion techniques in a porcine model.
OBJECTIVE
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 mug/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.
Krueger
Thorsten
T
Department of Thoracic Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Kuemmerle
Andrea
A
Kosinski
Marek
M
Denys
Alban
A
Magnusson
Lennard
L
Stupp
Roger
R
Delaloye
Angelika Bischof
AB
Klepetko
Walter
W
Decosterd
Laurent
L
Ris
Hans-Beat
HB
Dusmet
Michael
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D002407:Catheterization, Swan-Ganz; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D004317:Doxorubicin / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008168:Lung / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D008863:Microspheres; D023421:Models, Animal; D015609:Organotechnetium Compounds; D011651:Pulmonary Artery; D011877:Radionuclide Imaging; D012039:Regional Blood Flow; D013552:Swine; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D015609:Organotechnetium Compounds; C109881:dithio-bisphosphine tc99m; D004317:Doxorubicin