Exercise-induced rhabdomyolysis mechanisms and prevention: A literature review

Abstract

Exercise-induced rhabdomyolysis (exRML), a pathophysiological condition of skeletal muscle cell damage that may cause acute renal failure and in some cases death. Increased Ca²⁺ level in cells along with functional degradation of cell signaling system and cell matrix have been suggested as the major pathological mechanisms associated with exRML. The onset of exRML may be exhibited in athletes as well as in general population. Previous studies have reported that possible causes of exRML were associated with excessive eccentric contractions in high temperature, abnormal electrolytes balance, and nutritional deficiencies possible genetic defects. However, the underlying mechanisms of exRML have not been clearly established among health professionals or sports medicine personnel. Therefore, we reviewed the possible mechanisms and correlated prevention of exRML, while providing useful and practical information for the athlete and general exercising population.

Keywords: Acute renal failure; Calcium (Ca2+); Creatine kinase; Myoglobin (Mb); Rhabdomyolysis.

Fig. 1

The pathophysiological mechanism of rhabdomyolysis focusing on the increase of Ca²⁺. A: Deficiency of ATP due to high intensity exercise and continuous muscle contraction could induce the dysfunction of Na⁺-K⁺ ATPase, causing subsequent activation of reverse mode Na⁺-Ca²⁺ exchanger; B: Depolarization of sarcolemma and T-tubule by an action potential could activate dihydropyridine receptor and promote the secretion of Ca²⁺ via ryanodine receptor in sarcoplasmic reticulum; C: The increase of Ca²⁺ due to Ca²⁺ diffused by the rupture of sarcolemma from trauma; D: The entry of store-operated Ca²⁺ through transient receptor potential Channel 1 or transient receptor potential Channel 3 with reduced levels of Ca²⁺ in the sarcoplasmic reticulum; E: The secretion of Ca²⁺ (Ca²⁺-induced Ca²⁺ release) from sarcoplasmic reticulum in accordance with the increase of Ca²⁺ in sarcoplasm. → represents activation; represents inhibition, represents candidate mechanisms in the regulation of Ca²⁺. ATP = adenosine triphosphate; CICR = Ca²⁺-induced Ca²⁺ release; DHPR = dihydropyridine receptor; NCX_R = Na⁺-Ca²⁺ exchanger; PLA₂ = phospholipase A₂; ROS = reactive oxygen species; SOCE = store-operated Ca²⁺ entry; SR = sarcoplasmic reticulum; TRPC = transient receptor potential cation channels.