Prolonged exercise mainly depends on aerobic metabolism, unlike high-intensity exercise, which relies more on anaerobic sources of energy. Fatigue during prolonged exercise has been associated with depletion of glycogen stores in muscle and liver and with hypoglycemia. Intramuscular glycogen provides 50% of the energy during the first 30 minutes of submaximal exercise but drops to <20% after 1 hour. Blood glucose makes a smaller contribution, providing only 10% of total energy used. Although circulating fatty acids may provide an energy source during prolonged exercise, fatigue will set in before these fat stores are completely exhausted.
In prolonged exercise, the heat generated during aerobic ATP resynthesis imposes a high thermoregulatory demand on the animal. Only 20%–25% of the total energy produced by the muscles is converted to mechanical energy, leaving 75%–80% of that energy that must be removed as heat. Physiologic responses to heat production include sweating and/or panting to remove excess heat from the body. Complications from these compensatory mechanisms include dehydration,acid base and electrolyte disturbances (which are implicated as causes of fatigue), exhaustion, and even death (which can occur after prolonged exercise).