title: Contraction-induced muscle damage in humans following calcium channel blocker administration.
abstract: Following contraction-induced damage of skeletal muscle there is a loss of calcium homeostasis. Attenuating the damage-induced rise in myocellular calcium concentration may reduce proteolytic activation and attenuate other indices of damage; calcium channel blockers have been shown to be effective in this regard. The effect of administration of a calcium channel blocker (CCB), amlodipine, on indices of muscle damage following a unilateral 'damage protocol', during which subjects performed 300 maximal isokinetic (0.52 rad s(-1)) eccentric contractions with the knee extensors was investigated. The design was a randomized, double-blind crossover. On one occasion, prior to the damage protocol, subjects consumed CCB for 7 days prior to and for 7 days following the damage protocol. Biopsies were taken from the vastus lateralis prior to (baseline) and following the damage protocol at 4 h and 24 h post-damage. Isometric peak knee extensor torque was reduced (P < 0.05) immediately post-, 24 h post- and 48 h post-damage protocol compared to pre-exercise values with no effect of treatment. Desmin disruption was attenuated (P < 0.05) with CCB versus placebo at 4 h post-damage. Z-band streaming was significantly (P < 0.05) elevated compared to baseline at both times post-damage, but was lower with CCB at 4 h (P < 0.05). Damage resulted in increased inflammatory cell (macrophage) infiltration into skeletal muscle at both 4 h and 24 h post-damage, with no effect of CCB. Neutrophil number was elevated by the damage protocol, but was higher at 24 h post-damage in the CCB condition (P < 0.05). Creatine kinase (CK) activity was higher (P < 0.05) at 24 h and 48 h following the damage protocol compared to baseline, with no effect of treatment. In conclusion, the reduction in desmin disruption and Z-band streaming indicates that CCB attenuated, or delayed, the contraction-induced damage to sarcomeric proteins.
authors.affiliation: Department of Kinesiology (Exercise Metabolism Research Group), McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Beaton
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Phillips
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002452:Cell Count; D003402:Creatine Kinase / Q000378:metabolism; D018592:Cross-Over Studies; D003893:Desmin / Q000378:metabolism; D004311:Double-Blind Method; D006801:Humans; D007537:Isometric Contraction; D008264:Macrophages / Q000473:pathology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology; D009504:Neutrophils / Q000473:pathology; D013997:Time Factors; D019415:Torque
chemical_list: D002121:Calcium Channel Blockers; D003893:Desmin; D017311:Amlodipine; D003402:Creatine Kinase