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Section 2 describes Types of Contractions, shortening, isometric, and lengthening and the differences in the force development by each. The interactive roles of decreased usage and aging are covered in Section 3: Age- Related Muscle Wasting and Muscle Weakness and the condition of physical frailty is discussed. Section 4 focuses on Late-Onset Muscle Soreness described by Hough in 1902 and gaining widespread attention in the 1980s. The development of the concepts: Contraction-Induced Injury and Force Deficit are discussed in Section 5. Section 6 clarifies The Cause of the Contraction Induced Injury as a function of interactions between homogeneity of sarcomere strengths within a muscle and the severity of lengthening contraction protocols. Section 7 elaborates on the sig- nificance of the stability of the sarcomeres within fibers and the Contribution of Lateral Transmission of Force to Contraction-Induced Injury. Section 8, the Role of Contraction-Induced Injury in Wasting and Weakness contrasts the impact of contraction-induced injury on young and healthy and on elderly and frail subjects. J.A. Faulkner (*) and S.V. Brooks Departments of Biomedical Engineering and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-2200, USA e-mail: jafaulk@umich.edu C.L. Mendias Departments of Orthopaedic Surgery and the School of Kinesiology, University of Michigan, Ann Arbor, MI 48109-2200, USA C.S. Davis Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-2200, USA Role of Contraction-Induced Injury in Age-Related Muscle Wasting and Weakness John A. Faulkner, Christopher L. Mendias, Carol S. Davis, and Susan V. Brooks 374 J.A. Faulkner et al. The final Section 9: Measures to Prevent Contraction-Induced Injury emphasizes the positive aspects of utilizing lengthening contractions in training programs for both young and old participants. Keywords Contraction-induced injury • Delayed-onset muscle soreness • Muscle wasting • Muscle weakness • Lengthening contraction • Eccentric contraction • Muscle repair • Muscle regeneration • Force deficit • Muscle conditioning 1 Structure of Skeletal Muscles and Skeletal Muscle Fibers Skeletal muscles are composed of muscle fibers organized into motor units innervated by a motor nerve. In humans, single muscles range from small finger flexor muscles in the hands with fewer than 100 motor units and around 100 muscle fibers per motor unit on average to the gastrocnemius muscles in the lower leg composed of almost 600 motor units and close to 2,000 fibers per motor unit (Feinstein et al. 1955). Each individual muscle fiber within a motor unit contains myofibrils that consist of myosin filaments surrounded by and overlapping with thin actin filaments that are anchored in the z-discs at either end of sarcomeres. The globular head of the myosin molecules are capable of binding to sites on the thin actin filaments when a muscle fiber receives an action potential and there is a release of calcium from intracellular calcium stores. The myosin cross-bridges then proceed through a driving stroke that, under circumstances when the muscle is unloaded, or loaded with a resistance that can be moved, draws the thin filaments past the thick filaments in a movement that brings the z-discs together and shortens the length of sarcomeres. If the muscle is held at a fixed length and activated, cross-bridges cycle generating force without filament sliding and sarcomere shortening. Finally, if while activated, the muscle is stretched by a load greater than that generated by the cycling cross-bridges, cross-bridges are strained prior to release and re-attachment. 2 Types of Contractions When a muscle is activated by action potentials, the muscle fibers in the activated motor units attempt to shorten. Whether the fibers actually shorten, remain at the same length, or are lengthened depends on the interaction between the force gener- ated by the muscle and the load on the muscle. Consequently, skeletal muscles make three types of contractions – a shortening contraction, wherein the load on the muscle is less than the force generated by the muscle and the activated muscle fibers shorten (Fig. 1, Panel a); an isometric contraction, wherein the load on the muscle is either immoveable, or equivalent to the force generated by the muscle 375Role of Contraction-Induced Injury in Age-Related Muscle Wasting and Weakness and the activated muscle remains activated at a fixed length (Fig. 1, Panel b); or a lengthening contraction, wherein the load on the muscle is greater than the force generated by the muscle and the muscle is lengthened (Fig. 1, Panel c). The terms concentric and eccentric contractions are now in wide usage for shortening and lengthening contractions, respectively. Although the terms concentric and eccentric contractions are useful clinically, these terms have no intrinsic meaning in terms of the characteristics of the contractions that limb muscles make. Thus, throughout this chapter the terms shortening, isometric, and lengthening will be used to describe the type of a specific contraction. shortening isometric lengthening Biceps muscle shortens during contraction Biceps muscle remains at fixed length during contraction Biceps muscle lengthens during contraction Force > Load Force = Load Force < Load 90 100 110 0 100 Length (%L f ) Force (%P o ) a d e bc Fig. 1 The three types of contractions that single fibers, motor units and whole skeletal muscles are able to perform are dependent on the interaction of the force developed by the muscle and the load against which the muscle is attempting to shorten. A shortening contraction (a) occurs when the force is greater than the load. During a shortening contraction, the velocity of shortening is load dependent, with the greater the load the lower the velocity of shortening. During a shortening contraction, a muscle performs ‘work’. An isometric contraction (b) occurs when the force devel- oped by the muscle equals the load or under conditions when the load is immovable. A lengthen- ing contraction (c) results when the load on the muscle is greater than the force developed by the muscle (Modified from Vander, Sherman 2001, Luciano Human Physiology, Figs 11–31, page 320, McGraw-Hill. Reproduced with permission of The McGraw-Hill Companies.) The changes in the lengths of the muscle are displayed during each of the three types of contractions. Tracings of the displacements initiated by a servo motor lever arm (d) and the forces developed (e) by a maximally activated muscle measured by a force transducer. L f , fiber length that results in maxi- mum force; P o , maximum isometric tetanic force (Reprinted with permission from Faulkner et al. 2007, Wiley) . isometric, and lengthening and the differences in the force development by each. The interactive roles of decreased usage and aging are covered in Section 3: Age- Related Muscle Wasting and Muscle. Muscle repair • Muscle regeneration • Force deficit • Muscle conditioning 1 Structure of Skeletal Muscles and Skeletal Muscle Fibers Skeletal muscles are composed of muscle fibers organized. or equivalent to the force generated by the muscle 375Role of Contraction-Induced Injury in Age-Related Muscle Wasting and Weakness and the activated muscle remains activated at a fixed length