**10. The metabolic hypotheses: The role of insufficient mitochondrial respiration**

In the course of physical exercise the mitochondrial respiration appears high together with the synthesis and hydrolysis of the ATP. This situation is well balanced from a physiological point of view in the course of moderate exercise in which, the muscular fibers in activity, manage to maintain the concentration of ATP near to the base values (Krisanda et al.,1988). However, in the course of intense and prolonged exercise, a certain reduction in the concentration of energetic phosphates constantly occurs (Krisanda et al.,1988) and the possibility that this event occurs inside some specific compartments of the fiber represents a concrete and reasoned hypothesis which could explain the initial events of the mechanism of muscular lesion. For example, in the case in which a drop in ATP levels occurs near the Ca++ - ATPase on a level of the sarcoplasmatic reticulum or of the sarcolemma, the removal of Ca++ from the cytoplasm could result compromised, causing in such a way an increase in cytosolic Ca++. To this end there exists important experimental evidence which show that, to maintain an optimal state of cellular function, it is of vital importance to maintain an optimal functionality of the Ca++ pump (Duncan, 1987). Also in this field, some studies have shown how a drop in the cellular energetic provision may lead to a release of Ca++ from the sarcoplasmatic reticulum (Duchen et al., 1990). Some physiological evidence would show that the deficit of mytochondrial respiration inside the muscular fiber, cannot be considered the same way as an initial event in the onset of muscular damage; these affirmations are based on the fact that, a given level of production of force and /or mechanical power by the muscle, generated through an eccentric contraction, would result less costly than it is for the same level of production of force and /or generated power through a concentric or isometric contraction (Infante et al., 1964; Curtin and Davies, 1970; Bonde- Peterson et al., 1972) Despite this, it is the eccentric contraction the type of contractile muscular behavior which show higher harmful potential towards the integrity of the muscular structure (Asmussen, 1956; Armstrong et al., 1983; Newham et al., 1983; Armstrong, 1984; Ebbeling and Clarkson, 1989; Stauber, 1989). This lack of linking between metabolic cost and harmful event in the course of an eccentric contraction, would indicate, according to some authors, that the etiology of the muscular lesion would not lead to an insufficient production of ATP. Some authors have shown how there are no changes in levels of ATP, CP or in the pH after an injury, even though 24 hours after intense exercise we may register a significant increase in inorganic phosphate levels (Aldridge et al., 1986) At the same time, it is reasonable to expect that during a series of concentric contractions the muscular pH is lower than what it would be during an eccentric contraction. This could represent another indirect test of the fact that the lowering of the pH cannot, in itself, make up the initial factor of muscular damage. In this sense there exist experiments which show how, on isolated muscle, we may induct muscular damage also in the presence of neutral pH (between 7.3 and 7.6) with an average of 3mmol of lactate per liter (Duncan, 1987) Despite this it is of extreme importance to underline that these studies, and the consequential hypotheses, even though logical and rational, do not make up the indisputable test of the fact that the depletion of ATP or the lowering of the pH, are not implied in the process which carries to the muscular damage, but how rather they show that the muscular damage can come about also in absence of these assumptions of metabolic order (Armstrong et al., 1991). Particular attention must be placed on the fact that these specific situation of " metabolic unevenness", may be focal inside the fiber, reason for which in a well defined area of muscular fiber we may observe essential depletions of energetic phosphates and /or accumulation of lactate, which, on the contrary, are not observed in the rest of the muscular belly. So, even though definite demonstrations are missing of the fact that muscular damage recognizes its etiological cause in an insufficient mytochondrial respiration ratio, in bibliography there are not missing studies which speculate how the muscular damage, above all against the pure glycolytic fibers, at least on an animal model, is amenable to the contextual eccentric mechanism to a metabolic situation predispos‐ ing the damage itself (Liebere and Friden, 1988). In effect, a higher rational hypothesis in this sense is that which sees the intermittent anoxia, of which the muscle suffers during an intense series of eccentric contractions, as the cause of the drop in muscle pH to which follows a potential structural fragility situation both of the contractile tissue and of the connective tissue inside the muscle itself (Armstrong et al., 1991). So generally, a marginal fatigue may make up, at least from a theoretical point of view, a predisposing situation to muscular damage, even if a precise estimate of the role of fatigue in the harmful mechanism at the expense of the skeletal muscle, is objectively difficult.

**Figure 7.** In a muscle exposed to a series of intense eccentric contractions, a capillary vasoconstriction may happen which can, in itself, be the cause of an intermittent and transitory anoxia inside the muscle belly itself. The drop if the efficiency of the mechanism of mitochondrial respiration, would cause a drop in the production of ATP provided by the aerobic mechanism, which would induce an even higher involvement in the energetic production of the anaerobic lactate mechanism. This, together with the loss of efficiency of the heat regulator mechanisms due to the phenomena of vasoconstriction, would cause a drop in the pH and an increase of the muscular temperature, factors which would lead to an increase in the fragility both of the myofibrils and the of the sustaining connective tissue predisposing, in

Etiology, Biology and Treatment of Muscular Lesions

http://dx.doi.org/10.5772/56602

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Another consequence of the increase in metabolism during exercise is represented by the high production of free radicals (Packer, 1986; Jenkins, 1988; Matsunaga et al., 2003; Kon et al., 2008). Even though in many situations the increased production of free radicals is controlled by a wide variety of enzymes and of anti-oxidant molecules (Xu et al., 1997; Kon et al.,2008), in other circumstances this protective mechanism may result inefficient (Demopoulos, 1973b; Jenkins, 1988; Horakova et al., 2005). An uncontrollable production of free radicals may cause damage on a cellular level through an oxidation mechanism of phospholipids (Demopoulos, 1973; Blake et al., 1987) of DNA, (Cochrane et al., 1988), of carbohydrates (Blake et al., 1987) and of proteins (Tappel, 1973; Wolffe et al., 1986). The lipoperoxidation of the lipidic membrane may alter the normal permeability of the barrier of the sarcolemma (Quintanihla et al., 9182), allowing in such a way an abnormal molecular diffusion, in particular of Ca++ and of intra‐ muscular enzymes (Braughler, 1988); the inactivity of this enzyme can in fact perturb the homeostasis of the Ca++ inside the muscular fiber and cause, consequentially, the activity of a

such a way, the muscle to harmful event (Armstrong et al., 1991).

**11. The production of free radicals**

**Figure 7.** In a muscle exposed to a series of intense eccentric contractions, a capillary vasoconstriction may happen which can, in itself, be the cause of an intermittent and transitory anoxia inside the muscle belly itself. The drop if the efficiency of the mechanism of mitochondrial respiration, would cause a drop in the production of ATP provided by the aerobic mechanism, which would induce an even higher involvement in the energetic production of the anaerobic lactate mechanism. This, together with the loss of efficiency of the heat regulator mechanisms due to the phenomena of vasoconstriction, would cause a drop in the pH and an increase of the muscular temperature, factors which would lead to an increase in the fragility both of the myofibrils and the of the sustaining connective tissue predisposing, in such a way, the muscle to harmful event (Armstrong et al., 1991).
