No improvement in perfusion and oxygenation of experimental tumors upon application of vasodilator drugs

Abstract

The oxygen deficiency seen in solid tumors is predominantly caused by an insufficient O2 supply as a result of inadequate tumor perfusion. The aim of this study was to analyze whether a number of vasodilator drugs might be suitable to increase tumor perfusion and consequently improve the oxygenation status of experimental tumors. Rats with s.c. DS-sarcomas were treated with either Na+-nitroprusside (7-25 microg x min(-1) x kg(-1) BW) or nifedipine (10 microg x min(-1) x kg(-1) BW). Red blood cell (RBC) flux was assessed continuously using laser-Doppler flowmetry and mean tumor pO2 was measured polarographically using O2-sensitive catheter electrodes. Systemic application of the vasodilator drugs resulted in a dose-dependent decrease in MABP. In parallel, tumor perfusion was reduced linearly with falling MABP resulting in a decrease in RBC flux by approximately 40%. Resistance to flow did not change during the infusion indicating that these drugs have no impact on tumor vessel diameter. With decreasing tumor perfusion, tumor pO2 was reduced parallel to the MABP drop. This effect was more distinct with Na+-nitroprusside than with nifedipine due to the more pronounced fall in MABP. The vasodilator drugs studied are not suitable for dilation of tumor vessels either because the tumor vasculature lacks contractile wall elements or because the vessels are already maximally dilated.