Skip to main content
Log in

Mechanisms of Exercise-Induced Muscle Fibre Injury

  • Review Article
  • Published:
Sports Medicine Aims and scope Submit manuscript

Summary

Exercise for which a skeletal muscle is not adequately conditioned results in focal sites of injury distributed within and among the fibres. Exercise with eccentric contractions is particularly damaging. The injury process can be hypothesised to occur in several stages. First, an initial phase serves to inaugurate the sequence. Hypotheses for the initial event can be categorised as either physical or metabolic in nature. We argue that the initial event is physical, that stresses imposed on sarcolemma by sarcomere length inhomogeneities occurring during eccentric contractions cause disruption of the normal permeability barrier provided by the cell membrane and basal lamina. This structural disturbance allows Ca++ to enter the fibre down its electrochemical gradient, precipitating the Ca++ overload phase. If the breaks in the sarcolemma are relatively minor, the entering Ca++ may be adequately handled by ATPase pumps that sequester and extrude Ca++ from the cytoplasm (‘reversible’ injury). However, if the Ca++ influx overwhelms the Ca++ pumps and free cytosolic Ca++ concentration rises, the injury becomes ‘irreversible’. Elevations in intracellular Ca++ levels activate a number of Ca++-dependent proteolytic and phospholipolytic pathways that are indigenous to the muscle fibres, which respectively degrade structual and contractile proteins and membrane phospholipids; for instance, it has been demonstrated that elevation of intracellular Ca++ levels with Ca++ ionophores results in loss of creatine kinase activity from the fibres through activation of phospholipase A2 and subsequent production of leukotrienes. This autogenetic phase occurs prior to arrival of phagocytic cells, and continues during the inflammatory period when macrophages and other phagocytic cells are active at the damage site. The phagocytic phase is in evidence by 2 to 6 hours after the injury, and proceeds for several days. The regenerative phase then restores the muscle fibre to its normal condition. Repair of the muscle fibres appears to be complete; the fibres adapt during this process so that future bouts of exercise of similar type, intensity, and duration cause less injury to the muscle.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abbot BC, Aubert XM. Changes of energy in a muscle during very slow stretches. Proceedings of the Royal Society B 139: 104–117, 1951

    Article  Google Scholar 

  • Abbot BC, Aubert XM, Hill AV. The absorption of work by a muscle stretched during a single twitch or tetanus. Proceedings of the Royal Society B 139: 86–104, 1951

    Article  Google Scholar 

  • Abdel-Latif AA. Calcium-mobilizing receptors, polyphosphoinositides, and the generation of second messengers. Pharmacological Reviews 38: 227–272, 1986

    PubMed  CAS  Google Scholar 

  • Aldridge R, Cady EB, Jones DA, Obletter G. Muscle pain after exercise is linked with an inorganic phosphate increase as shown by 31P NMR. Bioscience Reports 6: 663–667,1986

    Article  PubMed  CAS  Google Scholar 

  • Allen TJA, Noble D, Reuter H (Eds). Sodium-calcium exchange, Oxford University Press, Oxford, 1989

    Google Scholar 

  • Arkhipenko YV, Pisarev VA, Kagan VE. Modification of enzymatic system for Ca2+ transport in sarcoplasmic reticulum during lipid peroxidation: systems for generation and regulation of lipid peroxidation in skeletal and heart muscles. Biokhimiya 48: 1261–1270, 1983

    CAS  Google Scholar 

  • Armstrong RB. Mechanisms of exercise-induced delayed onset muscular soreness: a brief review. Medicine and Science in Sports and Exercise 16: 529–538, 1984

    PubMed  CAS  Google Scholar 

  • Armstrong RB. Muscle damage and endurance events. Sports Medicine 3: 370–381, 1986

    Article  PubMed  CAS  Google Scholar 

  • Armstrong RB. Initial events in exercise-induced muscular injury. Medicine and Science in Sports and Exercise 22: 429–435, 1990

    PubMed  CAS  Google Scholar 

  • Armstrong RB, Laughlin MH, Rome L, Taylor CR. Metabolism of rats running up and down an incline. Journal of Applied Physiology 55: 518–521, 1983a

    PubMed  CAS  Google Scholar 

  • Armstrong RB, Ogilvie RW, Schwane JA. Eccentric exercise-induced injury to rat skeletal muscle. Journal of Applied Physiology 54: 80–93, 1983b

    PubMed  CAS  Google Scholar 

  • Arroyo O, Rosso JP, Vargas O, Gutiérrez JM, Cerdas L. Skeletal muscle necrosis induced by a phospholipase A2 isolated from the venom of the coral snake Micrurus nigrocinctus nigrocinctus. Comparative Biochemistry and Physiology 87B: 949–952, 1987

    CAS  Google Scholar 

  • Ashby MF, Jones DRH. Engineering materials 1: an introduction to their properties and applications, Pergamon Press, 1988

    Google Scholar 

  • Asmussen E. Observations on experimental muscular soreness. Acta Rheumatologica Scandinavica 2: 109–116, 1956

    PubMed  CAS  Google Scholar 

  • Axelrod J, Burch RM, Jelsema CL. Receptor-mediated activation of phospholipse A2 via GTP-binding proteins: arachidonic acid and its metabolites as second messengers. TINS 11: 117–123, 1988

    PubMed  CAS  Google Scholar 

  • Baracos VE, Greenberg RE, Goldberg AL. Calcium ions and the regulation of intracellular protein breakdown in muscle. In Endo M & Ebashi S (Eds) Calcium regulation in biological systems, Takeda Science Foundation 1984

    Google Scholar 

  • Barnett JG, Ellis S. Prostaglandin E2 and the regulation of protein degradation in skeletal muscle. Muscle Nerve 10: 556–559, 1987

    Article  PubMed  CAS  Google Scholar 

  • Bhattacharya SK, Crawford AJ, Thakar JH, Johnson PL. Pathogenetic roles of intracellular calcium and magnesium in membrane-mediated progressive muscle degeneration in Duchenne muscular dystrophy. In Fiskum G (Ed.) Cell calcium metabolism, pp. 513–525, Plenum, New York, 1989

    Chapter  Google Scholar 

  • Bigland-Richie B, Woods JJ. Integrated electromyogram and oxygen uptake during positive and negative work. Journal of Physiology (Lond.) 260: 267–277, 1976

    Google Scholar 

  • Blake DR, Allen RE, Lunec J. Free radicals in biological systems — a review oriented to inflammatory processes. British Medical Bulletin 43: 371–385, 1987

    PubMed  CAS  Google Scholar 

  • Bonde-Petersen F, Knuttgen HG, Henriksson J. Muscle metabolism during exercise with concentric and eccentric contractions. Journal of Applied Physiology 33: 792–795, 1972

    PubMed  CAS  Google Scholar 

  • Bonde-Petersen F, Nielsen B, Levin Nielsen S, Vangaard L. 133Xe clearance from musculus quadriceps femoris during concentric and eccentric bicycle exercise at different temperatures and loads. Acta Physiologica Scandinavica 79: 10A, 1970

    PubMed  CAS  Google Scholar 

  • Boobis AR, Fawthrop DJ, Davies DS. Mechanisms of cell toxicity. Current Opinion in Cell Biology 2: 231–237, 1990

    Article  PubMed  CAS  Google Scholar 

  • Boveris A, Cadenas E, Stoppani AOM. Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. Biochemical Journal 156: 435–444, 1976

    PubMed  CAS  Google Scholar 

  • Braughler JM. Calcium and lipid peroxidation. In Halliwell B (Ed.) Oxygen radicals and tissue injury pp. 99–104, Federation of American Societies for Experimental Biology, Bethesda, 1988

    Google Scholar 

  • Buja LM, Burton KP, Hagler HK, Willerson JT. Quantitative X-ray microanalysis of the elemental composition of individual myocytes in hypoxic rabbit myocardium. Laboratory Investigation 68: 872–882, 1983

    CAS  Google Scholar 

  • Buja LM, Willerson JT. Role of membrane dysfunction and altered calcium homeostasis in the pathogenesis of irreversible myocardial injury. In Fiskum G (Ed.) Cell calcium metabolism, pp. 551–559, Plenum, New York, 1989

    Chapter  Google Scholar 

  • Bullard B, Sainsbury G, Miller N. Digestion of proteins associated with the Z-disc by calpain. Journal of Muscle Research and Cell Motility 11: 271–279, 1990

    Article  PubMed  CAS  Google Scholar 

  • Busch WA, Stromer MH, Goll DE, Suzuki A. Ca2+-specific removal of Z lines from rabbit skeletal muscle. Journal of Cell Biology 52: 367–381, 1972

    Article  PubMed  CAS  Google Scholar 

  • Byrd SK, Bode AK, Klug GA. Effects of exercise of varying duration on sarcoplasmic reticulum function. Journal of Applied Physiology 66: 1383–1389, 1989a

    PubMed  CAS  Google Scholar 

  • Byrd SK, McCutcheon LJ, Hodgson DR, Gollnick PD. Altered sarcoplasmic reticulum function after high-intensity exercise. Journal of Applied Physiology 67: 2072–2077, 1989b

    PubMed  CAS  Google Scholar 

  • Cadenas E, Boveris A, Ragan CI, Stoppani AOM. Production of Superoxide radicals and hydrogen peroxide by NADH-ubiqui-none reductase and ubiquinol-cytochrome c reductase from beef heart mitochondria. Archives of Biochemistry and Biophysics 180: 248–257, 1977

    Article  PubMed  CAS  Google Scholar 

  • Carafoli E. The homeostasis of calcium in heart cells. Journal of Molecular and Cell Cardiology 17: 203–212, 1985

    Article  CAS  Google Scholar 

  • Carlson BM, Faulkner JA. The regeneration of skeletal muscle fibers following injury: a review. Medicine and Science in Sports and Exercise 15: 187–198, 1983

    Article  PubMed  CAS  Google Scholar 

  • Carpenter S. The roles of calcium and sodium in muscle necrosis. In Sellin et al. (Eds) Neuromuscular junction pp. 459–465, Elsevier Science Publishers, 1989

    Google Scholar 

  • Carpenter S, Karpati G. Segmental necrosis and its demarcation in experimental micropuncture injury of skeletal muscle fibers. Journal of Neuropathology and Experimental Neurology 48: 154–170, 1989

    Article  PubMed  CAS  Google Scholar 

  • Casella C. Tensile force in total striated muscle, isolated fiber and sarcolemma. Acta Physiologica Scandinavica 21: 380–401, 1951

    Article  Google Scholar 

  • Chang J, Musser JH, McGregor H. Phospholipase A2: function and pharmacological regulation. Biochemical Pharmacology 36: 2429–2436, 1987

    Article  PubMed  CAS  Google Scholar 

  • Chapman RA. A rise in intracellular sodium would seem to pre-dispose the heart to the calcium paradox. Journal of Molecular and Cellular Cardiology 22: 503–505, 1990

    Article  PubMed  CAS  Google Scholar 

  • Cheah KS, Cheah AM. Malignant hyperthermia: molecular defects in membrane permeabilty. Experientia 41: 656–661, 1985

    Article  PubMed  CAS  Google Scholar 

  • Ciechanover A, Gonen H, Elias S, Mayer A. Degradation of proteins by the ubiquitin-mediated proteolytic pathway. New Biologist 2: 227–234, 1990

    PubMed  CAS  Google Scholar 

  • Cochrane CG, Schraufstatter IU, Hyslop P, Jackson J. Cellular and biochemical events in oxidant injury. In Halliwell B (Ed.) Oxygen radicals and tissue injury, pp. 49–54, Federation of American Societies for Experimental Biology, Bethesda, 1988

    Google Scholar 

  • Colomo F, Lambardi V, Piazzesi G. The mechanisms of force enhancement during constant velocity lengthening in tetanized single fibres of frog muscle. Advances in Experimental Medicine and Biology 226: 489–502, 1988

    PubMed  CAS  Google Scholar 

  • Cooper CL, O’Callahan CM, Hosey MM. Phosphorylation of dihydropyridine-sensitive calcium channels from cardiac and skeletal muscle. In Fiskum G (Ed) Cell calcium metabolism, pp. 65–73, Plenum, New York, 1989

    Chapter  Google Scholar 

  • Cullen MJ, Fulthorpe JJ. Phagocytosis of the A band following Z line and I band loss: its significance in skeletal muscle breakdown. Pathology 138: 129–143, 1982

    Article  CAS  Google Scholar 

  • Curtin NA, Davies RE. Chemical and mechanical changes during stretching of activated frog skeletal muscle. Cold Spring Symposium on Quantitative Biology 37: 619–626, 1970

    Article  Google Scholar 

  • Davies CTM, White MJ. Muscle weakness following eccentric work in man. Pflügers Archiv 392: 168–171, 1981

    Article  PubMed  CAS  Google Scholar 

  • Dayton WR, Reville WJ, Goll DE, Stromer MH. A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Partial characterization of the purified enzyme. Biochemistry 15: 2159–2167, 1976

    Article  PubMed  CAS  Google Scholar 

  • Dayton WR, Schollmeyer JV, Chan AC, Allen CE. Elevated levels of a calcium-activated muscle protease in rapidly atrophying muscles from vitamin E-deficient rabbits. Biochemica et Biophysica Acta 584: 216–230, 1979

    Article  CAS  Google Scholar 

  • Del Maestro RF. An approach to free radicals in medicine and biology. Acta Physiologica Scandinavica (Suppl.) 492: 153–168, 1980

    Google Scholar 

  • Delp MD, Duan C, Hayes DA, Allen G, Armstrong RB. Effects of muscle stretch on mitochondrial Ca2+ concentration. Medicine and Science in Sports and Exercise 21: S66, 1989

    Article  Google Scholar 

  • Demopoulos HB. The basis of free radical pathology. Federation Proceedings 32: 1859–1861, 1973a

    PubMed  CAS  Google Scholar 

  • Demopoulos HB. Control of free radicals in biologic systems. Federation Proceedings 32: 1903–1907, 1973b

    PubMed  CAS  Google Scholar 

  • D’Haese J, Rutschmann M, Dahlmann B, Hinssen H. Activity of a gelsolin-like actin modulator in rat skeletal muscle under protein catabolic conditions. Biochemical Journal 248: 397–402, 1987

    PubMed  Google Scholar 

  • Donnelly AE, McCormick K, Maughan RJ, Whiting PH, Clarkson PM. Effects of a non-steroidal anti-inflammatory drug on delayed onset muscle soreness and indices of damage. British Journal of Sports Medicine 22: 35–38, 1988

    Article  PubMed  CAS  Google Scholar 

  • Driscoll J, Goldberg AL. Skeletal muscle proteasome can degrade proteins in an ATP-dependent process that does not require ubiquitin. Proceedings of the National Academy of Science USA 86: 787–791, 1989

    Article  CAS  Google Scholar 

  • Duan C, Delp MD, Hayes DA, Delp PD, Armstrong RB. Rat skeletal muscle mitochondrial [Ca2+] and injury from downhill walking. Journal of Applied Physiology 68: 1241–1251, 1990a

    PubMed  CAS  Google Scholar 

  • Duan C, Hayes DA, Armstrong RB. Effects of Ca2+ and verapamil on muscle injury immediately after exercise. Medicine and Science in Sports and Exercise 22: S132, 1990b

    Google Scholar 

  • Duchen MR, Valdeolmillos M, O’Neill SC, Eisner DA. Effects of metabolic blockade on the regulation of intracellular calcium in dissociated mouse sensory neurones. Journal of Physiology (Lond.) 424: 411–426, 1990

    CAS  Google Scholar 

  • Duncan CJ. Role of calcium in triggering rapid ultrastructural damage in muscle: a study with chemically skinned fibres. Journal of Cell Science 87: 581–594, 1987

    PubMed  CAS  Google Scholar 

  • Duncan CJ. The role of phospholipase A2 in calcium-induced damage in cardiac and skeletal muscle. Cell Tissue Research 253: 457–462, 1988

    PubMed  CAS  Google Scholar 

  • Duncan CJ, Greenaway HC, Smith JL. 2,4-Dinitrophenol, lysosomal breakdown and rapid myofilament degradation in vertebrate skeletal muscle. Naunyn-Schmicdebergs Archives of Pharmacology 315: 77–82, 1980

    Article  CAS  Google Scholar 

  • Duncan CJ, Jackson MJ. Different mechanisms mediate structural changes and intracellular enzyme efflux following damage to skeletal muscle. Journal of Cell Science 87: 183–188, 1987

    PubMed  Google Scholar 

  • Duncan CJ, Rudge MF. Are lysosomal enzymes involved in rapid damage in vertebrate muscle cells? Cell Tissue Research 253: 447–455, 1988

    PubMed  CAS  Google Scholar 

  • Duncan CJ, Smith JL. The action of caffeine in promoting ultrastructural damage in frog skeletal muscle fibres. Naunyn-Schmicdeberg’s Archives of Pharmacology 305: 159–166, 1978

    Article  CAS  Google Scholar 

  • Duncan CJ, Smith JL, Greenaway HC. Failure to protect frog skeletal muscle from ionophore-induced damage by the use of the protease inhibitor leupeptin. Comparative Biochemistry and Physiology 63C: 205–207, 1979

    CAS  Google Scholar 

  • Ebbeling CB, Clarkson PM. Exercise-induced muscle damage and adaptation. Sports Medicine 7: 207–234, 1989

    Article  PubMed  CAS  Google Scholar 

  • Etlinger JD, Kameyama T, van der Westhuysen D, Erlij D, Matsumoto K. Roles of calcium and tension in the regulation of protein turnover in muscle. In Guba et al. (Eds) Mechanism of muscle adaptation to functional requirements, pp. 241–253, Pergamon, New York, 1981

    Google Scholar 

  • Exton JH. Mechanisms of action of calcium-mobilizing agonists: some variations on a young theme. FASEB Journal 2: 2670–2676, 1988

    PubMed  CAS  Google Scholar 

  • Faulkner JA, Jones DA, Round JM. Injury to skeletal muscles of mice by forced lengthening during contractions. Quarterly Journal of Experimental Physiology 74: 661–670, 1989

    PubMed  CAS  Google Scholar 

  • Faust KB, Chiantella V, Vinten-Johansen J, Meredith JH. Oxygen-derived free radical scavengers and skeletal muscle ischemic/reperfusion injury. American Surgeon 54: 709–719, 1988

    PubMed  CAS  Google Scholar 

  • Fisher AB. Intracellular production of oxygen-derived free radicals. In Halliwell B (Ed.) Oxygen radicals and tissue injury, Federal American Society for Experimental Biology, Bethesda, 1988

    Google Scholar 

  • Fitzpatrick FA, Murphy RC. Cytochrome P-450 metabolism of arachidonic acid: formation and biological actions of ‘epoxygenase’-derived eicosanoids. Pharmacological Reviews 40: 229–241, 1989

    Google Scholar 

  • Francis KT, Hoobler T. Effects of aspirin on delayed muscle soreness. Journal of Sports Medicine and Physical Fitness 27: 333–337, 1987

    PubMed  CAS  Google Scholar 

  • Fridén J, Sjöström M, Ekblom B. A morphological study of delayed muscle soreness. Experientia 37: 506–507, 1981

    Article  PubMed  Google Scholar 

  • Fridén J, Sjöström M, Ekblom B. Myofibrillar damage following intense eccentric exercise in man. International Journal of Sports Medicine 4: 170–176, 1983

    Article  PubMed  Google Scholar 

  • Furuno K, Goldberg AL. The activation of protein degradation in muscle by Ca2+ or muscle injury does not involve a lysosomal mechanism. Biochemical Journal 237: 859–864, 1986

    PubMed  CAS  Google Scholar 

  • Gallant EM, Goettl VM. Effects of calcium antagonists on mechanical responses of mammalian skeletal muscles. European Journal of Pharmacology 177:259–265, 1985

    Article  Google Scholar 

  • Ganote CE, Humphrey SM. Effects of anoxic or oxygenated re-perfusion in globally ischemic, isovolumic, perfused rat hearts. American Journal of Pathology 120: 129–145, 1985

    PubMed  CAS  Google Scholar 

  • Gillis JM. Relaxation of vertebrate skeletal muscle. A synthesis of the biochemical and physiological approaches. Biochemica et Biophysica Acta 811: 97–145, 1985

    Article  CAS  Google Scholar 

  • Godfraind T, Miller R, Wibo M. Calcium antagonism and calcium entry blockade. Pharmacological Reviews 38: 321–417, 1986

    PubMed  CAS  Google Scholar 

  • Goodman MN. Differential effects of acute changes in cell Ca2+ concentration on myofibrillar and non-myofibrillar protein breakdown in the rat extensor digitorum longus muscle in vitro. Biochemical Journal 241: 121–127, 1987

    PubMed  CAS  Google Scholar 

  • Grinwald PM, Brosnahan C. Sodium imbalance as a cause of calcium overload in post-hypoxic reoxygenation injury. Journal of Molecular Cellular Cardiology 19: 487–495, 1987

    Article  CAS  Google Scholar 

  • Hansford RG. Relation between mitochondrial calcium transport and control of energy metabolism. Reviews of Physiology, Biochemistry and Pharmacology 102: 1–72, 1985

    Article  PubMed  CAS  Google Scholar 

  • Harris JB. Notexin: its actions on skeletal muscle. In Sellin et al. (Eds) Neuromuscular junction, pp. 467–479, Elsevier Science Publishers, 1989

    Google Scholar 

  • Hess ML, Manson NH, Okabe E. Involvement of free radicals in the pathophysiology of ischemic heart disease. Canadian Journal of Physiology and Pharmacology 60: 1382–1389, 1982

    Article  PubMed  CAS  Google Scholar 

  • Higuchi H, Umazume Y. Lattice shrinkage with increasing resting tension in stretched, single skinned fibers of frog muscle. Biophysical Journal 50: 385–389, 1986

    Article  PubMed  CAS  Google Scholar 

  • Hill SJ. Distribution, properties, and functional characteristics of three classes of histamine receptor. Pharmacological Reviews 42: 45–83, 1990

    PubMed  CAS  Google Scholar 

  • Hoffman EP, Brown Jr RH, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51: 919–928, 1987

    Article  PubMed  CAS  Google Scholar 

  • Hoffstein S, Weissmann G. Microfilaments and microtubules in calcium ionophore-induced secretion of lysosomal enzymes from human polymorphonuclear leukocytes. Journal of Cell Biology 78: 769–781, 1978

    Article  PubMed  CAS  Google Scholar 

  • Hough T. Ergographic studies in neuro-muscular fatigue. American Journal of Physiology 5: 240–266, 1901

    Google Scholar 

  • Infante AA, Klaupiks D, Davies RE. Adenosine triphosphate: changes in muscles doing negative work. Science 144: 1577–1578, 1964

    Article  PubMed  CAS  Google Scholar 

  • Irvine RF. The role of phospholipids in the generation and action of mediators. In Glaubert AM (Ed.) The control of tissue damage, Elsevier Science Publishers, 1988

    Google Scholar 

  • Ishiura S, Sugita H, Nonaka I, Imahori K. Calcium-activated neutral protease: its localization in the myofibril, especially at the Z-band. Journal of Biochemistry 87: 343–346, 1980

    PubMed  CAS  Google Scholar 

  • Jackson MJ, Edwards RHT. Biochemical mechanisms underlying skeletal muscle damage. In Benzi et al. (Eds) Biochemical aspects of physical exercise, Elsevier Science Publishers, 1986

    Google Scholar 

  • Jackson MJ, Jones DA, Edwards RHT. Measurements of calcium and other elements in muscle biopsy samples from patients with Duchenne muscular dystrophy. Clinico Chimica Acta 147: 215, 1985

    Article  CAS  Google Scholar 

  • Jackson MJ, Jones DA, Edwards RHT. Experimental skeletal muscle damage: the nature of the calcium-activated degenerative processes. European Journal of Clinical Investigations 14: 369–374, 1984

    Article  CAS  Google Scholar 

  • Jackson MJ, Wagenmakers JM, Edwards RHT. Effect of inhibitors of arachidonic acid metabolism on efflux of intracellular enzymes from skeletal muscle following experimental damage. Biochemical Journal 241: 403–407, 1987

    PubMed  CAS  Google Scholar 

  • Jenkins RR. Free radical chemistry: relationship to exercise. Sports Medicine 5: 156–170, 1988

    Article  PubMed  CAS  Google Scholar 

  • Julian FJ, Morgan DL. The effect on tension of non-uniform distribution of length changes applied to frog muscle fibres. Journal of Physiology 293: 379–392, 1979

    PubMed  CAS  Google Scholar 

  • Kagen LJ. Myoglobinuric syndromes. American Journal of Medical Science 264: 141–142, 1972

    Article  CAS  Google Scholar 

  • Kako KJ. Membrane damage caused by lipid peroxidation in myocardial ischemia. Jikei Medical Journal 32: 609–639, 1985

    CAS  Google Scholar 

  • Kameyama T, Etlinger JD. Calcium-dependent regulation of protein synthesis and degradation in muscle. Nature 279: 344–346, 1979

    Article  PubMed  CAS  Google Scholar 

  • Karpati G, Carpenter S. The deficiency of a sarcolemmal cytoskeletal protein (dystrophin) leads to the necrosis of skeletal muscle fibers in Duchenne-Becker dystrophy. In Sellin et al. (Eds) Neuromuscular junction, Elsevier Science Publishers, 1989

    Google Scholar 

  • Kaya J, Hong S. In Samuelsson B et al. (Eds) Advances in prostaglandin, thromboxane, and leukotriene research, pp. 580–583, Raven, New York, 1989

  • Katz B. The relation between force and speed in muscular contraction. Journal of Physiology 96: 45–64, 1939

    PubMed  CAS  Google Scholar 

  • Kilhoffer MC, Mely Y, Gerard D. The effect of plasma gelsolin on actin filaments: Ca2+ dependency of the capping and severing activities. Biochemical and Biophysical Research Communications 131: 1132–1138, 1985

    Article  PubMed  CAS  Google Scholar 

  • Klug GA, Tibbits GF. The effect of activity on calcium-mediated events in striated muscle. Exercise and Sports Science Reviews 16: 1–60, 1988

    CAS  Google Scholar 

  • Krisanda JM, Moreland TS, Kushmerick MJ. ATP supply and demand during exercise. In Horton ES & Terjung RL (Eds) Exercise, nutrition, and energy metabolism pp. 27–44, Macmillan, New York, 1988

    Google Scholar 

  • Kuipers H, Drukker J, Frederiks P, Geurten P, van Kranenburg G. Transient degenerative changes in muscle of untrained rats after non-exhaustive exercise. International Journal of Sports Medicine 4: 45–51, 1983

    Article  PubMed  CAS  Google Scholar 

  • Kuipers H, Keizer HA, Verstappen FTJ, Costill DL. Influence of a prostaglandin-inhibiting drug on muscle soreness after eccentric work. International Journal of Sports Medicine 6: 336–339, 1985

    Article  PubMed  CAS  Google Scholar 

  • Kwiatkowski DJ, Mehl R, Izumo S, Nadal-Ginard B, Yin HL. Muscle is the major source of plasma gelsolin. Journal of Biological Chemistry 263: 8329–8242, 1988

    Google Scholar 

  • Lane RD, Mellgren RL, Mericle MT. Subcellular localization of bovine heart calcium-dependent protease inhibitor. Journal of Molecular Cellular Cardiology 17: 863–872, 1985

    Article  CAS  Google Scholar 

  • Lefurgey A, Murphy E, Wagenknecht B, Ingram P, Lieberman M. Structural, biochemical, and elemental correlates of injury in cultured cardiac cells. In Fiskum G (Ed.) Cell calcium metabolism, pp. 571–580, Plenum, New York, 1989

    Chapter  Google Scholar 

  • Lehninger AL. Biochemistry, p. 477, Worth, New York, 1975

    Google Scholar 

  • Lemasters JJ, Nieminen A, Gores GJ, Wray BE, Herman B. Cytosolic free calcium and cell injury in hepatocytes. In Fiskum G (Ed.) Cell calcium metabolism, pp. 463–470, Plenum, New York, 1989

    Chapter  Google Scholar 

  • Leonard JP, Salpeter MM. Agonist-induced myopathy at the neuromuscular junction is mediated by calcium. Journal of Cell Biology 82: 811–819, 1979

    Article  PubMed  CAS  Google Scholar 

  • Lieber RL, Fridén J. Selective damage of fast glycolytic muscle fibres with eccentric contraction of the rabbit tibialis anterior. Acta Physiologica Scandinavica 133: 587–588, 1988

    Article  PubMed  CAS  Google Scholar 

  • Locke M, Noble EG, Atkinson BG. Exercising mammals synthesize stress proteins. American Journal of Physiology 258: C723–C729, 1990

    PubMed  CAS  Google Scholar 

  • López JR, Alamo L, Caputo C. The increase in metabolic rate associated with stretching in skeletal muscle might be related to an incrementin free [Ca2+]. Biophysical Journal 47: A378, 1985

    Google Scholar 

  • Malis CD, Boventre JV. Susceptibility of mitochondrial membranes to calcium and reactive oxygen species: implications for ischemic and toxic tissue damage. Progress in Clinical and Biological Research 282: 235–259, 1988

    PubMed  CAS  Google Scholar 

  • Matsumoto T, Okitani A, Kitamura Y, Kato H. Mode of degradation of myofibrillar proteins by rabbit muscle cathepsin D. Biochemica et Biophysica Acta 755: 76–80, 1983

    Article  CAS  Google Scholar 

  • Matthews W, Tanaka K, Driscoll J, Ichihara A, Goldberg AL. Involvement of the proteasome in various degradative processes in mammalian cells. Proceedings of the National Academy of Science USA 86: 2597–2601, 1989

    Article  CAS  Google Scholar 

  • Mauro A (Ed.). Muscle regeneration. Raven, New York, 1979

    Google Scholar 

  • McCully KK, Faulkner JA. Injury to skeletal muscle fibres of mice following lengthening contractions. Journal of Applied Physiology 59: 119–126, 1985

    PubMed  CAS  Google Scholar 

  • McCully KK, Faulkner JA. Characteristics of lengthening contractions associated with injury to skeletal muscle fibers. Journal of Applied Physiology 61: 293–299, 1986

    PubMed  CAS  Google Scholar 

  • McMahon TA. Muscles, reflexes, and locomotion, Princeton University Press, 1984

    Google Scholar 

  • McMillin JB, Madden MC. The role of calcium in the control of respiration by muscle mitochondria. Medicine and Science in Sports and Exercise 21: 406–410, 1989

    PubMed  CAS  Google Scholar 

  • Mellgren RL. Calcium-dependent proteases: an enzyme system active at cellular membranes? FASEB Journal 1: 110–115, 1987

    PubMed  CAS  Google Scholar 

  • Mellgren RL, Carr TC. The protein inhibitor of calcium-dependent proteases: purification from bovine heart and possible mechanisms of regulation. Archives of Biochemistry and Biophysics 225: 779–786, 1983

    Article  PubMed  CAS  Google Scholar 

  • Mellgren RL, Lane RD, Kakar SS. Isolated bovine myocardial sarcolemma and sarcoplasmic reticulum vesicles contain tightly bound calcium-dependent protease inhibitor. Biochemical and Biophysical Research Communications 142: 1025–1031, 1987

    Article  PubMed  CAS  Google Scholar 

  • Minneman KP. α-adrenergic receptor subtypes, inositol phosphates, and sources of cell Ca2+. Pharmacological Reviews 40: 87–119, 1988

    PubMed  CAS  Google Scholar 

  • Morgan DL. New insights into the behavior of muscle during active lengthening. Biophysical Journal 57: 209–221, 1990

    Article  PubMed  CAS  Google Scholar 

  • Morimoto RI, Tissières A, Geogropoulos C. The stress response, function of the proteins, and perspectives. In Morimoto RI (Ed.) Stress proteins in biology and medicine, pp. 1–36, Cold Spring Harbor Laboratory Press, 1990

    Google Scholar 

  • Murachi T, Tanaka K, Hatanaka M, Murakami T. Intracellular Ca2+-dependent protease (calpain) and its high-molecular-weight endogenous inhibitor (calpastatin). Advances in Enzyme Regulation 19: 407–424, 1981

    Article  CAS  Google Scholar 

  • Murphy E, London RE. In vivo NMR spectroscopy and cell injury. In Hodgson et al. (Eds) Reviews in biochemical toxicology, Vol. 9, Elsevier, 1988

    Google Scholar 

  • Murphy JG, Marsh JD, Smith TW. The role of calcium in ischemic myocardial injury. Circulation 75(Suppl. V): V15–V24, 1987

    PubMed  CAS  Google Scholar 

  • Nadel ER, Bergh U, Saltin B. Body temperature during negative work. Journal of Applied Physiology 33: 553–558, 1972

    PubMed  CAS  Google Scholar 

  • Nagatomo T, Sasaki M, Konishi T. Differences in lipid composition and fluidity of cardiac sarcolemma prepared from newborn and adult rabbits. Biochemical Medicine 32: 122–131, 1984

    Article  PubMed  CAS  Google Scholar 

  • Nelson TE. Cell calcium in malignant hyperthermia. In Fiskum G (Ed.) Cell calcium metabolism, pp. 507–511, Plenum, New York, 1989

    Chapter  Google Scholar 

  • Newham DJ, Jones DA, Ghosh G, Aurora P. Muscle fatigue and pain after eccentric contractions at long and short length. Clinical Science 74: 553–557, 1988

    PubMed  CAS  Google Scholar 

  • Newham DJ, Mills KR, Quigley BM, Edwards RHT. Pain and fatigue after concentric and eccentric muscle contractions. Clinical Science 64: 55–62, 1983

    PubMed  CAS  Google Scholar 

  • Nielsen B. Thermoregulation in rest and exercise. Acta Physiologica Scandinavica (Suppl.) 323: 1–74, 1969

    Article  CAS  Google Scholar 

  • Nielsen TB, Field JB, Dedman JR. Association of calmodulin with lysosomes. Journal of Cell Science 87: 327–336, 1987

    PubMed  CAS  Google Scholar 

  • Nohl H, Hordan W, Youngman RJ. Quinonones in biology: functions in electron transfer and oxygen activation. Advances in Free Radical Biology and Medicine 92: 211–279, 1986

    Article  Google Scholar 

  • Ogilvie RW, Armstrong RB, Baird KE, Bottoms CL. Lesions in the rat soleus muscle following eccentrically-biased exercise. American Journal of Anatomy 182: 335–346, 1988

    Article  PubMed  CAS  Google Scholar 

  • Ogilvie RW, Hoppeler H, Armstrong RB. Decreased muscle function following eccentric exercise in the rat. Medicine and Science in Sports and Exercise 17: 195, 1985

    Google Scholar 

  • Oishi K, Kuo CJ, Kuo JF. Potential second messenger role of lysophospholipids in regulating protein kinase C. In Yagi K & Miyazaki T (Eds) Calcium signal and cell response, pp. 47–56, Japan Science Society Press, Tokyo, 1989

    Google Scholar 

  • Orrenius S, McConkey DJ, Nicotera P. Role of calcium in oxidative cell injury. In Fiskum G (Ed.) Cell calcium metabolism, pp. 451–461, Plenum, New York, 1989

    Chapter  Google Scholar 

  • Packer L. Mitochondria, oxygen radicals and animal exercise. In (Ed.) Membranes and muscle, pp. 135–147, 1985

    Google Scholar 

  • Packer L. Oxygen radicals and antioxidants in endurance exercise. In Benzi G et al. (Eds) Biochemical aspects of physical exercise, pp. 73–92, Elsevier Science Publishers, 1986

    Google Scholar 

  • Packer L. Vitamin E, physical exercise and tissue damage in animals. Medical Biology 62: 105–109, 1984

    PubMed  CAS  Google Scholar 

  • Pahud P, Ravussin E, Acheson KJ, Jequier E. Energy expenditure during oxygen deficit of submaximal concentric and eccentric exercise. Journal of Applied Physiology 49: 16–21, 1980

    PubMed  CAS  Google Scholar 

  • Parsons D, Burton KP, Hagler HK, Willerson JT, Buja LM. Tension and electrolyte changes with Na+-K+ pump inhibition in rat papillary muscle. American Journal of Physiology 257: H942–H953, 1989

    PubMed  CAS  Google Scholar 

  • Paul J, Bekker AY, Durán WN. Calcium entry blockade prevents leakage of macromolecules induced by ischemia-reperfusion in skeletal muscle. Circulation Research 66: 1636–1642, 1990

    Article  PubMed  CAS  Google Scholar 

  • Pelham HRB. Functions of the hsp 70 protein family: an overview. In Morimoto RI (Ed.) Stress proteins in biology and medicine, pp. 287–299, Cold Spring Harbor Laboratory Press, 1990

    Google Scholar 

  • Peterson MW, Gruenhaupt D. A23187 increases permeability of MDCK monolayers independent of phospholipase activation. American Journal of Physiology 259: C69–C76, 1990

    PubMed  CAS  Google Scholar 

  • Phelps PC, Smith MW, Trump BF. Cytosolic ionized calcium and bleb formation following acute cell injury of cultured rabbit renal tubule cells. Laboratory Investigations 60: 630–642, 1989

    CAS  Google Scholar 

  • Philipson KD, Bersohn MM. Sodium-calcium exchange: calcium regulation at the sarcolemma. Advances in Experimental Medicine and Biology 194: 557–562, 1986

    Article  PubMed  CAS  Google Scholar 

  • Pontremoli S, Melloni E. Extralysosomal protein degradation. Annual Review of Biochemistry 55: 455–481, 1986

    Article  PubMed  CAS  Google Scholar 

  • Poole-Wilson PQ, Harding DP, Bourdillon PDV, Tones MA. Calcium out of control. Journal of Molecular Cellular Cardiology 16: 175–187, 1984

    Article  CAS  Google Scholar 

  • Popov EP. Engineering mechanics of solids, Prentice Hall, 1990

  • Publicover SJ, Duncan SJ, Smith JL. The use of A23187 to demonstrate the role of intracellular calcium in causing ultrastructural damage in mammalian muscle. Journal of Neuropathology and Experimental Neurology 37: 554–557, 1978

    Article  PubMed  CAS  Google Scholar 

  • Putney Jr JW, Takemura H, Hughes AR, Horstman DA, Thastrup O. How do inositol phosphates regulate calcium signaling? FASEB Journal 3: 1899–1905, 1989

    PubMed  CAS  Google Scholar 

  • Quintanilha AT, Packer L, Davies JM, Racanelli TL, Davies KJA. Membrane effects of vitamin E deficiency: bioenergetic and surface charge density studies of skeletal muscle and liver mitochondria. Annals of the New York Academy of Sciences 393: 32–47, 1982

    Article  PubMed  CAS  Google Scholar 

  • Rapoport SI. Mechanical properties of the sarcolemma and myoplasma in frog muscle as a function of sarcomere length. Journal of General Physiology 59: 559–585, 1972

    Article  PubMed  CAS  Google Scholar 

  • Renlund DG, Lakatta EG, Gerstenblith G. Sodium modulation of resting force, contractile properties, and metabolism with particular emphasis on its role in the development of calcium overload states. Advances in Experimental Medicine and Biology 194: 601–615, 1986

    Article  PubMed  CAS  Google Scholar 

  • Robertson SP, Johnson JD, Potter JD. The time-course of Ca2+ exchange with calmodulin, troponin, parvalbumin, and myosin in response to transient increases in Ca2+. Biophysical Journal 34: 559–569, 1981

    Article  PubMed  CAS  Google Scholar 

  • Rodemann HP, Goldberg AL. Arachidonic acid, prostaglandin E2 and F2a influence rates of protein turnover in skeletal and cardiac muscle. Journal of Biological Chemistry 257: 1632–1638, 1982

    PubMed  CAS  Google Scholar 

  • Rodemann HP, Waxman L, Goldberg AL. The Stimulation of protein degradation in muscle by Ca2+ is mediated by prostaglandin E2 and does not require the calcium-activated protease. Journal of Biological Chemistry 257: 8716–8723, 1982

    PubMed  CAS  Google Scholar 

  • Rosenthal W, Hescheler J, Trautwein W, Schultz G. Control of voltage-dependent Ca2+ channels by G protein-coupled receptors. FASEB Journal 2: 2784–2790, 1988

    PubMed  CAS  Google Scholar 

  • Rudge MF, Duncan CJ. Comparative studies on the role of calcium in triggering subcellular damage in cardiac muscle. Comparative Biochemistry and Physiology 77A: 459–468, 1984

    CAS  Google Scholar 

  • Schadewaldt P, Stapper NJ, Staib W. Effect of adrenergic agonists on phosphoinositide breakdown in rat skeletal muscle preparations. FEBS Letters 217: 45–48, 1987

    Article  PubMed  CAS  Google Scholar 

  • Scheuer W. Phospholipase A2-regulation and inhibition. Klinische Wochenschrift 67: 153–159, 1989

    Article  PubMed  CAS  Google Scholar 

  • Schlesinger MJ. Heat shock proteins. Journal of Biological Chemistry 265: 1211–1214, 1990

    Google Scholar 

  • Schultz E. Satellite cell behaviour during skeletal muscle growth and regeneration. Medicine and Science in Sports and Exercise 21: 5181–5186, 1989

    Google Scholar 

  • Schwane JA, Armstrong RB. Effect of training on skeletal muscle injury from downhill running in rats. Journal of Applied Physiology 55: 969–975, 1983

    PubMed  CAS  Google Scholar 

  • Schwartz WN, Bird JWC. Degradation of myofibrillar proteins by cathepsins B and D. Biochemical Journal 167: 811–820, 1977

    PubMed  CAS  Google Scholar 

  • Sembrowich WL, Quintinskie JJ, Li G. Calcium intake in mitochondria from different skeletal muscle types. Journal of Applied Physiology 59: 137–141, 1985

    PubMed  CAS  Google Scholar 

  • Snowdowne KE, Lee NKM. Subcontracture concentrations of potassium and stretch cause and increase in activity in intracellular calcium in frog skeletal muscle. Federation Proceedings 39: 1733, 1980

    Google Scholar 

  • Stainsby WN. Oxygen uptake for negative work, stretching contractions by in situ dog skeletal muscle. American Journal of Physiology 230: 1013–1017, 1976

    PubMed  CAS  Google Scholar 

  • Statham HE, Duncan CJ, Smith JL. The effect of the ionophore A23187 on the ultrastructure and electro-physiological properties of frog skeletal muscle. Cell Tissue Research 173: 193–209, 1976

    PubMed  CAS  Google Scholar 

  • Stauber WT. Eccentric action of muscles: physiology, injury, and adaptations. Exercise and Sports Science Reviews 17: 157–185, 1989

    CAS  Google Scholar 

  • Steenbergen C, Hill ML, Jennings RB. Cytoskeletal damage during myocardial ischaemia: changes in vinculin immunofluorescence staining during total in vitro ischemia in canine heart. Circulation Research 60: 478–486, 1987a

    Article  PubMed  CAS  Google Scholar 

  • Steenbergen C, Murphy E, Levy L, London RE. Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart. Circulation Research 60: 700–707, 1987b

    Article  PubMed  CAS  Google Scholar 

  • Tappel AL. Lipid peroxidation damage to cell components. Federation Proceedings 32: 1870–1874, 1973

    PubMed  CAS  Google Scholar 

  • Tibbits GF, Thomas MJ. Ca2+ transport across the plasma membrane of striated muscle. Medicine and Science in Sports and Exercise 21: 399–405, 1989

    PubMed  CAS  Google Scholar 

  • Tidball JG. Energy stored and dissipated in skeletal muscle basement membranes during sinusoidal oscillations. Biophysical Journal 50: 1127–1138, 1986

    Article  PubMed  CAS  Google Scholar 

  • Tidball JG, Daniel TL. Elastic energy storage in rigored skeletal muscle cells under physiological loading conditions. American Journal of Physiology 250: R54–R64, 1986

    Google Scholar 

  • Tiidus PM, Ianuzzo CD. Effects of intensity and duration of muscular exercise on delayed soreness and serum enzyme activities. Medicine and Science in Sports and Exercise 15: 461–465, 1983

    PubMed  CAS  Google Scholar 

  • Trump BF, Croker Jr BP, Mergner WJ. The role of energy metabolism, ion, and water shifts in the pathogenesis of cell injury. In Richter GW & Scarpelli DG (Eds) Cell membranes: biological and pathological aspects, pp. 84–128, Williams and Wilkins, Baltimore, 1971

    Google Scholar 

  • Trump BF, Berezesky IK. Role of ion regulation in cell injury, cell death, and carcinogenesis. In Fiskum G (Ed) Cell calcium metabolism, pp. 441–449, Plenum, New York, 1989

    Chapter  Google Scholar 

  • Turner PR, Westwood T, Regen CM, Steinhardt RA. Increased protein degradation results from elevated free calcium levels found in muscle from mdx mice. Nature 335: 735–738, 1988

    Article  PubMed  CAS  Google Scholar 

  • van der Vusse GJ, van Bilsen M, Reneman RS. Is phospholipid degradation a critical event in ischemia- and reperfusion-induced damage? News in Physiological Sciences 4: 49–53, 1989

    Google Scholar 

  • Vane J, Botting R. Inflammation and the mechanism of action of anti-inflammatory drugs. FASEB Journal 1: 89–96, 1987

    PubMed  CAS  Google Scholar 

  • Van Kuijk FJGM, Sevanian A, Handelman GJ, Dratz EA. A new role for phospholipase A2: protection of membranes from lipid peroxidation damage. Trends in Biochemical Sciences 12: 31–36, 1987

    Article  Google Scholar 

  • Varagic VM, Kentera D. Interactions of calcium, dibutyryl cyclic AMP, isoprenaline, and aminophylline on the isometric contraction of the isolated hemidiaphragm of the rat. Naunyn-Schmicdeberg’s Archives of Pharmacology 303: 47–53, 1978

    Article  CAS  Google Scholar 

  • Vihko V, Salminen A, Rantamäki J. Acid hydrolase activity in red and white skeletal muscle of mice during a two-week period following exhausting exercise. Pflügers Archiv 378: 99–106, 1978

    Article  PubMed  CAS  Google Scholar 

  • Wang K, Ramirez-Mitchell R. A network of transverse and longitudinal intermediate filaments is associated with sarcomeres of adult vertebrate skeletal muscle. Journal of Cell Biology 96: 562–570, 1983

    Article  PubMed  CAS  Google Scholar 

  • Warren JA, Packer L, Witt EH, Armstrong RB. Vitamin E and rat skeletal muscle injury from exercise. Medicine and Science in Sports and Exercise 22: S108, 1990

    Google Scholar 

  • Welch WJ. The mammalian stress reponse: cell physiology and biochemistry of stress proteins. In Morimoto RI (Ed) Stress proteins in biology and medicine, pp. 223–278, Cold Spring Harbor Laboratory Press, 1990

    Google Scholar 

  • Woledge RC, Curtin NA, Homsher E. Energetic aspects of muscle contraction. Monographies of the Physiological Society No. 41, 1985

  • Wolff SP, Garner A, Dean RT. Free radicals, lipids and protein degradation. Trends in Biochemical Sciences 11: 27–31, 1986

    Article  CAS  Google Scholar 

  • Wrogemann K, Pena SDJ. Mitochondrial calcium overload: a general mechanism for cell-necrosis in muscle diseases. Lancet 1: 672–674, 1976

    Article  PubMed  CAS  Google Scholar 

  • Zerba E, Komorowski TE, Faulkner J. Free radical injury to skeletal muscles of young, adult, and old mice. American Journal of Physiology 258: C429–C435, 1990a

    PubMed  CAS  Google Scholar 

  • Zerba E, Ridings EO, Faulkner JA. At different muscle temperatures, contraction-induced injury correlates with power absorption. FASEB Journal 4: A815, 1990b

    Google Scholar 

  • Zimmerman ANE, Hülsmann WC. Paradoxical influence of calcium ions on the permeability of the cell membranes of the isolated rat heart. Nature 211: 646–647, 1966

    Article  PubMed  CAS  Google Scholar 

  • Zubrzycka-Gaarn EE, Bulman DE, Karpati G, Burghes AH, Belfall B, et al. The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle. Nature 333: 466–469, 1988

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Armstrong, R.B., Warren, G.L. & Warren, J.A. Mechanisms of Exercise-Induced Muscle Fibre Injury. Sports Med 12, 184–207 (1991). https://doi.org/10.2165/00007256-199112030-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00007256-199112030-00004

Keywords

Navigation