Lactate: metabolic fuel or poison for racehorses?

The sarcolemma of mammalian skeletal muscle possesses two main types of lactate transporters, monocarboxylate transporter (MCT) 1 and MCT4. The functions of these transporters have been partly determined in rodent skeletal muscle; MCT1 is highly expressed in oxidative muscle and is primarily involved in facilitating the extraction of lactate from the extracellular fluid, while MCT4 is almost exclusively expressed in glycolytic muscle and primarily facilitates the net efflux of lactate (Bonen, 2001). It is expected that this functional arrangement persists across mammalian species, including humans and horses. The Thoroughbred racehorse is one of nature's most gifted athletes, capable of utilizing nearly every muscle in its body when at a full gallop. The massive metabolic demands of going from rest to a gallop in a matter of seconds require exceedingly high rates of ATP provision. Owing to the sluggishness of the aerobic system to provide the required ATP and the limited ATP that can be supplied via the phosphocreatine system, the requirement is therefore for very high rates of glycolytic ATP production. In galloping horses, the high rates of lactate production result in muscle and plasma lactate concentrations of ∼43 and 30 mmol l−1, respectively (Harris et al. 1987). Excessive accumulation of lactate within muscle contributes to intracellular acidosis and fatigue (Cairns, 2006), but lactate accumulation is a necessary evil associated with high speed. The paper by Hatta and colleagues in this issue of Experimental Physiology (Kitaoka et al. 2011) brings together basic muscle physiology of horses and the applied science of horse racing. They demonstrated that 6 months of high-intensity exercise training in Thoroughbred horses increased the muscle content of MCT4. This result is consistent with the idea that exercise performance can be enhanced when glycolytic muscle enhances its ability to remove lactate from within contracting cells. This may be particularly important because of the negative effects of intracellular lactate accumulation on muscle acidosis and fatigue processes. What is important is that these characteristics are enhanced with appropriate training, and that enhanced rates of lactate removal are associated with a slowing of muscle fatigue and improved race performance. Thus, it can be expected that the superior Thoroughbred racehorse is one that is well endowed with fast-twitch glycolytic fibres capable of generating glycolytic ATP at the fastest rates, is capable of tolerating the largest increases in intracellular and blood lactate, and has muscle fibres capable of removing lactate from contracting muscle at high rates. But what to do with all the lactate? If we assume that 40% of the racehorse's 500 kg body mass is muscle, most of which is actively contracting during a race, and that the extracellular fluid volume of this horse is 100 l, one computes a total lactate production of ∼9000 mmol, of which ∼6 mol is within muscle and 3 mol within extracellular fluid and blood cells. The body would be loath to waste this valuable carbohydrate fuel source that is so readily oxidized by muscle and other cells (Miller et al. 2002). It is, therefore, of interest that in these horses the high-intensity training also resulted in an increased expression of MCT1 and increased citrate synthase activity (Kitaoka et al. 2011). This finding suggests an upregulation of mechanisms for muscular lactate disposal and oxidation that would be likely to reside mainly within the oxidative fibre population. Such mechanisms would be expected to facilitate the acid–base and functional recovery of previously contracting muscle by effectively shuttling lactate from glycolytic to oxidative fibres (Brooks, 2009). Finally, while 9000 mmol is physiologically a lot of lactate, representing a minimum of 18,000 mmol of glycolytic ATP production, this number yields a mass of only 100 g of lactate produced in a horse weighing 500 kg. That such high rates of lactate production can benefit performance, and yet such high lactate concentrations impair performance (Cairns, 2006), remains a conundrum of exercise physiology. The racehorse, however, appears to be on the right track, able to enhance the metabolic removal of the lactate in the face of high rates of its production.