The relationship between extracellular lactate and tumour pH in a murine tumour model of ischaemia-reperfusion

Abstract

We have studied the relationship between extracellular lactate (LACTe) and extracellular pH (pHe) in murine tumours after vascular occlusion (clamping) followed by reperfusion. In tumours occluded at ambient room temperature, LACTe, measured by microdialysis, increased linearly with time and correlated strongly with the acidification of the extracellular compartment (r=0.97, P<0.03, n=4). Significant decrease in LACTe was evident following removal of occlusion at room temperature and is consistent with vascular reperfusion. Occlusion at 35 degrees C, i.e. to maintain tumour temperature during occlusion, resulted in an initial increase in LACTe, which mirrored a rapid reduction in pHe. However further reductions in pHe occurred without increase in LACTe. During vascular occlusion, tumour adenine nucleotide pool decreased and AMP accumulated. AMP subsequently decreased in the 35 degrees C group and this may contribute to the observed differences in accumulation of LACTe, and capacity to recover from vascular occlusion, between the two treatment groups. These data show that extracellular lactate concentration is a good predictor for tumour pH when adequate energy sources are available within the tumour. However, under conditions of more severe stress, resulting in abolition of primary energy stores and cell death, the pHe continues to decline in the absence of a corresponding accumulation of extracellular lactate. This emphasizes the fact that other processes, apart from lactate production, can contribute to reduction in extracellular pH.