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Bart P. van Putte, MD, Jeroen M. H

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1 Modified Approach of Administering Cytostatics to the Lung: More Efficient Isolated Lung Perfusion 
Bart P. van Putte, MD, Jeroen M.H. Hendriks, MD, PhD, Gunther Guetens, PhD, Gert de Boeck, PhD, Ernst A. de Bruijn, PharmD, Paul E.Y. van Schil, MD, PhD, Gert Folkerts  The Annals of Thoracic Surgery  Volume 82, Issue 3, Pages (September 2006) DOI: /j.athoracsur Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Diagram of the experimental design. (ILuP = isolated lung perfusion.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 Gemcitabine effluent levels (plus standard error) in function of perfusion time for a concentration escalating schedule of the inflowing perfusate. The concentration-escalating schedule of gemcitabine delivered by isolated lung perfusion (ILuP) resulted in a rapid augmentation of the gemcitabine effluent levels between 3 and 6 minutes exposure for all groups. A 43% (for the 1.3 mg/mL group) to 51% (for the 6.7 mg/mL group) uptake into the lung tissue occurred. Each concentration-escalating step resulted in significantly higher lung levels and areas under the curve (p < 0.01) except for 6.7 mg/mL inflow concentration (0.05 < p < 0.01 compared with 5.3 mg/mL). (Boxes = 6.7 mg/mL; triangles = 5.3 mg/mL; circles = 4.0 mg/mL; small diamonds = 2.7 mg/mL; large diamonds = 1.3 mg/mL.). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 1. Gemcitabine lung levels (plus standard error) in function of the inflowing perfusate levels after 30 minutes of isolated lung perfusion. As a function of the initial perfusate concentration, 43% to 51% uptake into the lung tissue occurred. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 1. The upper line shows gemcitabine lung levels (plus standard error) as a function of time during isolated lung perfusion (ILuP [p = 0.024, 6 versus 30 minutes (boxes); upper line]). In the lower curve, a rapid washout after ILuP is demonstrated during a 5-minute flush followed by further diminishing lung levels after restored circulation (circles) until 60 minutes of normal blood circulation. However, delayed clamp release (triangles) after ILuP followed by a 5-minute washout resulted in significantly higher lung levels and areas under the curve up to 60 minutes (456% at 30 minutes, p = 0.002, and 828% at 60 minutes, p = 0.03; middle curve). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions


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