Fatigue during High-intensity Exercise
For all intensities of exercise, there is a degree of anaerobic metabolism, but for brief, high-intensity exercise, anaerobic metabolism predominates. Catabolism of creatine phosphate and glycogen is the anaerobic source of energy during high-intensity exercise. This type of exercise at an individual animal’s highest attainable speed cannot be maintained for >30–40 seconds. Thereafter, fatigue occurs and the animal slows down.
The contribution of aerobic or anaerobic energy pathways during exercise depends on the duration and energy demands of the event. In short, intense exercise lasting 20–30 seconds (eg, Quarter horse races [400 m], some Greyhound races), 60% of energy demands is supplied by anaerobic sources. For intense exercise at maximal speeds for a longer duration (eg, Standardbred or Thoroughbred races [1,600–2,100 m] lasting 1–3 min), it has been estimated that the energy supply is 20%–30% anaerobic. In contrast, events lasting many hours (eg, endurance races for horses, camels, and dogs) have >90% of energy demands met by aerobic sources.
During brief, high-intensity exercise, fatigue is secondary to engagement of muscle fibers that heavily rely on anaerobic metabolism. The higher the intensity, the greater the anaerobic demand. Fatigue is the result of an increase in hydrogen ions, lactate, inorganic phosphate, ammonia, and ADP, and a decrease in ATP, phosphocreatine, and pH in active muscle cells. Clinically, fatigue is initially identified by a decrease in exercise intensity or a drop in the maximal speed.
As anaerobic metabolism increases, lactate production is directly correlated to the percentage of type IIB muscle fibers present and corresponds to the accumulation of protons in the muscle tissue. Intracellular acidosis caused by lactate accumulation has a negative feedback effect on the glycolytic enzymes required for energy production and mitochondrial respiration, resulting in a decline in ATP concentrations. Lack of ATP prevents calcium recycling through the sarcoplasmic reticulum, resulting in accumulation of calcium in the sarcoplasm and slowing of the relaxation phase of muscle contraction. Acidosis also interferes with excitation-contraction coupling by interfering with calcium binding to troponin C, reducing the ability of the muscles to contract. Unfortunately, there is no correlation between muscle lactate concentration and placement in a race, or plasma lactate concentrations and performance indexes.
A decrease in muscle ATP after maximal exercise has been noted in conjunction with high muscle lactate concentrations. For high-intensity exercise, eg, a Thoroughbred race lasting 2 min, intramuscular stores of ATP can decrease from 14% to 50%. Depletion of ATP varies by muscle fiber type. In type I fibers, depletion is negligible, whereas in type IIB fibers, ATP loss is significant. Low levels of ATP impair optimal functioning for muscle contraction, reuptake of calcium by the sarcoplasmic reticulum, and the sodium potassium exchange. Fatigue is associated with depletion of phosphocreatine stores and accumulation of ADP and inorganic phosphate. A correlation between stride length and muscle ADP accumulation has been seen at the time of fatigue.
Increased ADP concentration results in accumulation of AMP, inosine monophosphate, allantoin, ammonia, and uric acid in horses. In treadmill studies, the decrease in muscle ATP during intense exercise is correlated with an increase in plasma uric acid concentration 30 min after exercise. Running time during treadmill tests is correlated with uric acid concentrations after exercise. Significant but low correlations have also been found between racing performance of Standardbred pacers and uric acid concentrations after a race.
Ammonia accumulation in plasma is correlated to decreased ATP and increased muscle lactate. It has been postulated that ammonia accumulation in the plasma may contribute to fatigue. However, infusion with ammonium acetate during treadmill exercise until fatigue did not significantly affect time to fatigue, suggesting plasma ammonia levels do not have a role in fatigue during intense exercise.
Similar to ATP depletion, muscle glycogen concentration decreases up to 30% after a single exercise bout and by as much as 50% with repeated bouts of intense exercise. Again, depletion varies between muscle fiber types, with greater depletion seen in type IIB muscle fibers. Glycogen depletion may play a role in fatigue, in that horses that perform repeated bouts of exercise before an anaerobic exercise session may be at increased risk of fatigue because of the slow rate of glycogen repletion in this species.
During high-intensity exercise, the normal equilibrium between release of potassium from recruited muscle and uptake by inactive muscle fibers is lost, resulting in a continual increase of extracellular potassium until the onset of fatigue. Changes in the ratio of intracellular to extracellular potassium across the sarcolemma alter the resting membrane potential and decrease sarcolemma excitability and the ability to generate an action potential. Reduced excitability contributes to reduced calcium release by the sarcoplasmic reticulum (a process that requires ATP) and a consequent reduction in the force of muscle contraction. This loss of force may relate to the idea of an inherent safety mechanism, in that plasma potassium rapidly declines after cessation of exercise by reuptake into the now inactive muscle.
Intracellular acidosis as a result of lactate accumulation has been blamed for the decrease in efficiency or force of muscle contractions. However, in vitro research has demonstrated a protective effect of lactic acidosis or hydrogen ions in maintaining sarcolemma function and muscle force production in the face of potassium shifts within the cell and plasma associated with intense exercise.
Fatigue during high-intensity exercise is also influenced by environmental conditions. Intense exercise in hot conditions is associated with earlier onset of fatigue, due to increased blood flow to the skin for thermoregulation at the expense of cardiac output and oxygen delivery to the exercising muscle. Attenuation of normal increases in muscle blood flow during exercise in hot environments has been suggested as a contributor to the onset of fatigue. There is also a central effect of high temperatures, resulting from increased blood temperature at the hypothalamus. Early onset of fatigue in hot conditions is thought to be a protective response to avoid heat stroke.