THE RELATIONSHIP BETWEEN EXTRACELLULAR LACTATE AND TUMOR PH IN A MURINE TUMOR-MODEL OF ISCHEMIA-REPERFUSION

We have studied the relationship between extracellular lactate (LACT(e )) and extracellular pH (pH(e)) in murine tumours after vascular occlu sion (clamping) followed by reperfusion. In tumours occluded at ambien t room temperature, LACT(e), measured by microdialysis, increased line arly with time and correlated strongly with the acidification of the e xtracellular compartment (r=0.97, P<0.03, n=4). Significant decrease i n LACT(e) was evident following removal of occlusion at room temperatu re and is consistent with vascular reperfusion. Occlusion at 35 degree s C, i.e. to maintain tumour temperature during occlusion, resulted in an initial increase in LACT(e), which mirrored a rapid reduction in p H(e). However further reductions in pH(e) occurred without increase in LACT(e). During vascular occlusion, tumour adenine nucleotide pool de creased and AMP accumulated. AMP subsequently decreased in the 35 degr ees C group and this may contribute to the observed differences in acc umulation of LACT(e), 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 conditi ons of more severe stress, resulting in abolition of primary energy st ores and cell death, the pH(e) 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 con tribute to reduction in extracellular pH.