Comment on: “Revised Approach to the Role of Fatigue in Anterior Cruciate Ligament Injury Prevention: A Systematic Review with Meta-analyses”

Abstract

We read with great interest the systematic review and metaanalysis by Benjaminse et al. [1], which aimed to propose an optimized approach for measuring the role of fatigue in anterior cruciate ligament (ACL) injury prevention. The authors presented approaches that can be considered to increase the resistance to fatigue and, thus, decrease injury risk [1]. Among these approaches are anaerobic and aerobic fitness. The authors conclude that an increase in overall anaerobic and aerobic fitness may offer protection to the athlete against injury, and serves as a moderator to decrease injury risk [1]. However, prolonged force depression after mechanically demanding eccentric contractions is largely independent of anaerobic and aerobic fitness [2, 3]. The forced lengthening of an activated skeletal muscle has been termed eccentric contraction, which is essential, for example, for opposing the high centrifugal forces experienced by skiers in carved turns [4]. Within muscle fibers, fatigue is generally related to increased energy demands, in which effective adenosine triphosphate (ATP) resynthesis is needed to match the dramatically increased ATP consumption during contractions [5]. Adequate ATP delivery to ATP-consuming proteins is essential for normal cell function and integrity, because depletion of ATP would have devastating consequences [5]. Obviously, mechanisms to prevent these catastrophic consequences of ATP depletion exist within muscle fibers [5]. These mechanisms involve, on the one hand, effective metabolic systems to resynthesize ATP and, on the other hand, a fatigue-induced decline in ATP consumption [5]. The latter fatigue mechanisms, which inhibit contractiondependent ATP consumption, were the major focus of a recent review [5]. Importantly, effective metabolic systems, i.e., a high anaerobic and/or aerobic capacity, may increase fatigue resistance and, thus, decrease ACL injury in metabolically demanding exercises. By contrast, mechanically demanding eccentric muscle activity is a titin-based, and not O2 -ATP coupled, contraction form [6]. Therefore, only around one-quarter of the amount of O2 is needed for the same load in eccentric muscle activity [6]. Titin has long been recognized as a mechanical protein in muscle cells that has a main function as a molecular spring in the contractile units, the sarcomeres [7]. Mechanically active titin spring elements are regions consisting of immunoglobulin-like (Ig) domains and the PEVK element, which is rich in proline (P), glutamate (E), valine (V), and lysine (K) residues. Both the PEVK segment and all Ig-domain regions represent important spring elements in titin [7]. In short, when the sarcomeres of a skeletal muscle are stretched, the titin Ig domain segments and the PEVK region extend [7]. Titin domain folding against a force represents a potential source of work production in muscles that presumably acts synchronously with the actomyosin contractile mechanism [7]. As such, titin is an active component in the sarcomere that helps to maximize work output without consuming ATP [7]. Titin Ig domain folding under force as a source of work production contradicts the notion that ATP depletion is a central factor underlying the impaired contractile function after mechanically demanding eccentric contractions [7]. Moreover, the mechanisms underlying prolonged force depression after mechanically demanding eccentric contractions are dissimilar to those after metabolically demanding contractions [2, 8]. Interestingly, the force depression after mechanically demanding eccentric contractions is similar in recreationally active subjects and * Arnold Koller [email protected]