Fatigue in Muscle and Nerve

While it is impossible to understand the subtleties of response decrement in the intact organism by reference to fatigue processes in muscle and peripheral nerve, certain features of these processes bear a relation to the more complicated phenomena. Fatigue is properly defined as a more or less complete loss of irritability and responsiveness in a tissue--a loss which is brought on by functional activity of the tissue and is recoverable through rest. When a muscle is exercised, there is a progressive decrease in the magnitude of response until further contraction becomes impossible. If the muscle is allowed to rest, or if its load is lightened, then contraction of that muscle will again be possible.

The primary condition for the loss of muscular responsiveness is the rapid accumulation of waste products. A more enduring effect probably results from the consumption of energygiving substances. Muscle fibers are able to carry on their vital activities by burning certain fuels, which they manufacture from food substances carried to them by the blood. The fuel molecules are split up and burned whenever the fiber contracts. The oxygen required to burn these products is taken from the blood; and the by products of the process, such as CO 2, are absorbed by the blood stream and carried to the lungs to be given off in the expired air. When contraction occurs frequently, the rate of the splitting-up process exceeds the rate of the burning-up or oxidative process. The toxic substances which result from this partial combustion accumulate on the muscle and act to lower its vitality and depress its irritability. Massage of the muscle will help restore irritability by speeding up circulation.

Extract from unfatigued muscles gave no such result. Ranke also attempted to prove that the fatigue toxins consist in known products of muscular metabolism. Since later work has confirmed his findings, it seems justifiable to consider that the active agents of fatigue are the split products of metabolism, chiefly lactic acid, carbon dioxide, and potassium phosphate acid. Prolonged muscle activity implies a lessened supply of oxygen, the chemical which resolves these split products. Since the two conditions are reciprocally related, fatigue can be described either in terms of an excess of split waste products, such as lactic acid, or in terms of a deficiency of oxygen; probably because our knowledge of the chemistry of fatigue is still so incomplete, it is usually referred to as oxygen deficiency.

When abnormal amounts of unburned waste products have accumulated in a muscle, they may be carried off by the blood and thus influence other muscles. This may explain the fact, brought out by ergograph experiments, that exercise of one group of muscles is likely to diminish the work output obtainable from other muscles. The return of irritability following complete fatigue is not to be explained solely in terms of a gradual reduction of fatigue toxins. Reduction of these toxins through absorption into the blood probably occurs at a fairly rapid rate. Even if the circulation remains intact, however, an interval of several hours must elapse before the muscle entirely regains its normal contractile powers. Apparently an additional factor is operative here; namely, that during prolonged exercise a muscle draws heavily upon its supply of energy-yielding material. The long recovery lag may, therefore, be due to the failure of the process of restoring this material to keep pace with its consumption. The accumulation of waste products and the lag in restoration of energy materials are not mutually exclusive effects but are produced by the same set of conditions, namely, prolonged exercise. The first is the more active effect; but the second is also of great importance to our understanding of muscle fatigue.

The probable seat of muscular fatigue has been the subject of considerable controversy. Late in the last century Waller 11 found that muscles rendered non-excitable by prolonged neural stimulation would still contract when stimulated directly. Prior to that time Benard 12 had shown that curare blocks conduction from nerve to muscle without destroying the activity of either. These results focused attention on the motor end-plate as the presumptive locus of fatigue. At first it was thought that in order to explain these results a specialized junctional tissue had to be postulated between the motor end-plate and the muscle fiber; but the failure to isolate this third tissue and the growing evidence that muscle fibers are themselves affected by split fatigue products and narcotics has made the hypothesis unlikely. A muscle which has been fatigued by prolonged stimulation of its motor nerve develops less than half the tension of an unfatigued muscle when both are stimulated directly; and drugs, such as veratrin, caffein, and curate, have a well-marked general effect upon muscle fibers. Perhaps the capillary network has been so arranged that oxygen cannot diffuse as rapidly in the region of the motor end-plate as elsewhere in the muscle fiber. This would then give the region about the end-plate the function of a safety-fuse, which could "blow out" to eliminate a nervous current before it did damage to the entire muscle fiber.

It is generally admitted that nerve cells and fibers do utilize some oxygen and fuel substances during activity; but the details of the process have not been very well worked out. If the nerve cell is made to function excessively, certain histological changes apparently occur. There is a probable increase in the size of the cell, a diminution of the Nissl bodies (chromatolysis), and even a displacement of the nucleus. Possibly, as in active muscle, lactic acid as well as carbon dioxide is formed. The amount of these waste accumulations during exercise is negligible, however; and even in experiments upon nerves deprived of their vascular connections it is practically impossible to produce the fatigue changes which are so characteristic of muscular tissue.

Although the structural changes in nerves consequent to exercise are little understood, there are acceptable evidences of fatigue on functional grounds. When a nerve is excited, it responds quickly, rests for a fraction of a second, and then is ready for normal response again. Normally, its processes of restoration are balanced against its processes of consumption. Lengthened refractory phase is probably analyzable into more fundamental metabolic processes, such as the exhaustion of available oxygen, the concentration of ionic changes, or the accumulation of minute amounts of split waste products.