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. 2002 Dec 2;87(12):1462-9.
doi: 10.1038/sj.bjc.6600611.

Nifedipine improves blood flow and oxygen supply, but not steady-state oxygenation of tumours in perfusion pressure-controlled isolated limb perfusion

O Thews  1 , M Hummel, D K Kelleher, B Lecher, P Vaupel
Affiliations

Nifedipine improves blood flow and oxygen supply, but not steady-state oxygenation of tumours in perfusion pressure-controlled isolated limb perfusion

O Thews et al. Br J Cancer. .

Abstract

Isolated limb perfusion allows the direct application of therapeutic agents to a tumour-bearing extremity. The present study investigated whether the dihydropyridine-type Ca(2+)-channel blocker nifedipine could improve blood flow and oxygenation status of experimental tumours during isolated limb perfusion. Perfusion was performed by cannulation of the femoral artery and vein in rats bearing DS-sarcoma on the hind foot dorsum. Perfusion rate was adjusted to maintain a perfusion pressure of 100-140 mmHg throughout the experiment. Following equilibration, nifedipine was continuously infused for 30 min (8.3 microg min(-1) kg(-1) BW). During constant-pressure isolated limb perfusion, nifedipine can significantly increase perfusion rate (+100%) and RBC flux (+60%) through experimental leg tumours. "Steal phenomena" in favour of the surrounding normal tissue and oedema formation were not observed. Despite the increased oxygen availability (+63%) seen upon application of this calcium channel blocker, nifedipine does not result in a substantial reduction of tumour hypoxia, most probably due to an increase in O(2) uptake with rising O(2) supply to the tumour-bearing hind limb. Nifedipine application during isolated limb perfusion can enhance tumour microcirculation and may therefore promote the delivery (pharmacokinetics) of anti-cancer drugs to the tumour and by this improve the efficacy of pressure-controlled isolated limb perfusion.

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Figures

Figure 1
Figure 1
Experimental set-up for isolated limb perfusion in the rat.
Figure 2
Figure 2
Perfusate flow rate during isolated limb perfusion upon application of nifedipine or vehicle alone (gray bar). Data represent mean±s.e.m. (n=number of perfusion experiments).
Figure 3
Figure 3
(A) RBC-flux and (B) resistance to flow (TVR) during isolated limb perfusion upon application of nifedipine. Data represent mean±s.e.m. (n=number of tumours investigated; the RBC flux value of each tumour was obtained by calculating the mean values from up to three individual probes located in central and peripheral regions of the tumour).
Figure 4
Figure 4
Changes of mean tumour pO2 during isolated limb perfusion upon application of nifedipine compared to the pO2 value immediately prior to the commencement of drug infusion. Data represent mean±s.e.m. (n=number of tumours investigated).
Figure 5
Figure 5
Correlation between O2 supply and O2 uptake during isolated limb perfusion.
See this image and copyright information in PMC

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