Rapid tracer lactate influx into canine skeletal muscle

This study evaluated the effects of various lactate transport inhibitors and competitors on rapid tracer lactate influx into the canine gastrocnemius- plantaris muscle (GP). GPs of 25 anesthetized dogs were perfused with red blood cell-free media in situ. At 0.9 mM lactate concentration ([La]), GP oxygen uptake (2.6 ± 0.1 ml · kg^-1 · min^-1) and net lactate output (- 0.039 ± 0.007 mmol · kg^-1 min^-1) were similar to values during blood perfusion. Rapid tracer lactate influx was inferred by a paired-tracer dilution method at nominal perfusate [La] values of 1, 5, 10, 25, and 50 mM. The maximal tracer influx rate (U(max)) decreased significantly with each increase in unlabeled [La]. A saturation effect was suggested by the fact that percent inhibition of U(max) began to reach a plateau at the higher unlabeled [La] values. The inhibition of U(max) was 20.5 ± 2.9% at 5 mM, 34.1 ± 3.3% at 10 mM, 47.3 ± 2.7% at 25 mM, and 56.1 ± 2.8% at 50 mM [La]. U(max) was also inhibited by various inhibitors/competitors of lactate transport as follows (%inhibition):50 mM α-cyano-4-hydroxy-cinnamate (69.2 ± 4.9%), 1.5 mM phloretin (25.4 ± 5.5%), 0.1 mM 4,4'- diisothiocyanostilbene-2,2'-disulfonic acid (0.3 ± 1.9%), 0.5 mM p- chloromercuribenzenesulfonic acid (72.9%), 0.5 mM furosemide (+2.8%), 25 mM pyruvate (52.4 ± 2.9%), and 50 mM DL-lactate (50.2 ± 4.0%). These experiments support the notion that lactate influx into canine skeletal muscle is a function of both a linear (possible diffusive) component and a Michaelis-Menten (carrier-mediated) component.