Thoroughbred horses susceptible to Recurrent Exertional Rhabdomyolysis have elevated skeletal muscle mitochondrial capacities

Recurrent Exertional Rhabdomyolysis (RER) is a skeletal muscle disease that can intermittently impede careers of equine athletes. Manifesting as episodes of muscular stiffness and degeneration, RER causes lost training and competition days. RER is associated with abnormal intracellular calcium (Ca 2+ ) regulation. Calcium released from the sarcoplasmic reticulum to initiate contraction may also be transported into mitochondria, which impacts energy production. RER-susceptible horses exhibit down-regulated mitochondrial proteins but upregulated mitochondrial genes. Thus, mitochondrial function may be impacted by Ca 2+ irregularities in RER horses. Fourteen race-fit female Thoroughbred horses were used to test the hypothesis that horses which had previously experienced at least 2 ER episodes (n = 8; mean ± SD 3.1 ± 1.1 yr) would have impaired skeletal muscle mitochondrial capacities compared to control racehorses (n = 6; 3.5 ± 1.4 yr). Gluteus medius samples were analyzed for oxidative phosphorylation ( P) and electron transfer ( E) capacities via high-resolution respirometry. Contrary to our hypothesis, integrative (per mg) NADH-linked P ( P N ), maximal P ( P NS ), maximal E ( E NS ) and succinate-linked E ( E S ) tended to be greater ( P ≤ 0.1) while intrinsic (relative to citrate synthase activity) P N and E S tended to be greater ( P ≤ 0.1) and P NS and E NS were greater ( P ≤ 0.03) in RER-susceptible compared to control horses. Horses susceptible to RER appeared to have greater skeletal muscle mitochondrial capacities, which might be consequent to aberrant intramuscular Ca 2+ handling in vivo. The clinical significance of this finding remains unclear but further investigation could lead to mitochondrially-targeted treatment and management strategies.