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Overview of Fatigue and Exercise in Animals


Amelia S. Munsterman

, DVM, PhD, DACVS, DACVECC, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University

Reviewed/Revised Apr 2019 | Modified Nov 2022

Muscular fatigue during exercise is the decline in the ability of a muscle to generate force of contraction, resulting in the inability of the animal to continue to perform at the same level of intensity. Alterations in cardiovascular parameters, serum electrolytes, and muscle tissue may be observed if physiologic compensatory mechanisms are exhausted. Treatment involves rest, rehydration, restoration of normal serum electrolyte concentrations, and cooling strategies. 

Fatigue may occur during both aerobic and anaerobic exercise and at submaximal effort. Factors that can affect the onset of fatigue include:

  • ambient environmental temperature

  • hydration status and serum electrolyte concentrations

  • external motivators

  • the animal's desire to work

As muscular effort increases, glycogen depletion, intracellular acidosis, and accumulation of metabolic byproducts will contribute to the onset of fatigue. Fatigue during exercise can also be the result of pathologic conditions, including diseases that affect oxygen uptake, energy metabolism, or neuromuscular function. This discussion focuses on muscular fatigue in healthy animals.

Pathophysiology of Fatigue in Animals

Fatigue is considered a normal consequence of exercise of prolonged duration or high intensity, and it is regarded as an intrinsic safety mechanism. Without the onset of fatigue, or if fatigue is delayed, structural damage to the myocytes and supportive tissues may occur. There are two types of fatigue: peripheral and central.

Peripheral fatigue is fatigue secondary to altered muscle function. The primary cause is failure of ATP to resynthesize, with accumulation of ADP and inorganic phosphate ions. Studies of muscle metabolism after exercise to identify peripheral fatigue have relied mainly on muscle biopsies and direct measurement of muscle glycogen, creatine phosphate, ATP, ADP, inosine monophosphate, inorganic phosphate, glycolytic intermediary products, pH, and other metabolites. Other studies have investigated the expression of mRNA in muscle tissue to monitor adaptations in gene expression of proteins that regulate oxygen-dependent metabolism, glucose metabolism, and fatty acid utilization.

Indirect serum biomarkers associated with peripheral fatigue that could be used clinically include:

  • lactate

  • ammonia

  • hypoxanthine and xanthine

  • markers of oxidative damage (thiobarbituric acid reactive substances, glutathione, and glutathione peroxidase)

  • inflammatory mediators (IL-1, TNF-α)

  • lymphocytes

Central fatigue is defined as an alteration in the signals arising from the CNS, directly decreasing performance by modifying the frequency of the action potential in the motor neurons. Central fatigue may occur secondary to pain, dyspnea, perceptions of exertion, hypoglycemia, hyperthermia, ammonia accumulation, increases in serotonin, altered amino acid metabolism, and changes in extracellular ions. Central fatigue is associated with:

  • decreased motivation

  • lethargy

  • loss of muscle coordination

However, the cause of central fatigue is multifactorial, and the response to these stimuli is highly variable. For example, some horses can continue endurance exercise at speed despite severe hyperthermia, dehydration, and plasma electrolyte disturbances.

Key Points

  • Fatigue results from the inability of the muscle to generate maximal force.

  • Fatigue is a physiologic protective mechanism activated to prevent injury.

  • Clinical signs of fatigue result from changes at the cellular level of the muscle tissues as well as alterations in nerve signaling pathways from the CNS.

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