The activity of the muscle tissue of mammalian animals is closely dependent upon a good supply of nutrition, and if its blood current be completely cut off by any means for a length of time, it loses its power of contracting. While the muscle remains in the body, and is kept warm and moist by the juices in the tissues, it will live a very considerable time without any blood flowing through it, and it at once regains its contractility when the blood stream is again allowed to flow through its vessels. This is seen when the circulation of a limb is brought to a standstill by means of a tourniquet or a tightly applied bandage. A mammalian muscle soon ceases to be irritable and dies when removed from the body, but its functional activity may be.renewed by passing an artificial stream of arterial blood through its vessels, and an isolated muscle may thus be made to contract repeatedly for a considerable time.

On the other hand, the muscle of a cold-blooded animal will remain alive for a long time - many hours - if kept cool and moist. When its functional activity is about to fade, it may be revived by means of an artificial stream of blood caused to flow through its vessels, just as in the case of the mammalian muscle.

Common experience teaches us that even when well supplied with blood our muscles become fatigued after very prolonged exertion, and are incapable of further action. This occurs all the more rapidly when anything interferes with the flow of blood through them, such as using our arms in an elevated position; the simple operation of driving in a screw overhead is soon followed by pain and fatigue in the muscles of the forearm, though the same amount of force could be exerted when the arms are in a lower posture, without the least feeling of fatigue.

The difficulties of experimenting with the muscles of mammals make the frog muscle the common material for investigation, and from it we learn the following facts: -

1. When removed from the body and deprived of its blood supply, the muscle of a cold-blooded animal slowly dies from want of nutrition. If it be placed under favorable circumstances, and allowed perfect rest, it may live twenty-four hours. If it be frequently excited to action, on the other hand, it rapidly loses its irritability, being worn out by fatigue.

2. From a muscle removed from a recently-killed animal, we learn, that even without a supply of blood the muscle tissue is capable of recovering from very well-marked fatigue, if it be allowed to rest for a little time, so that the muscle has in itself the material requisite for the recuperation.

The first question then is, What causes the loss of irritability which we call fatigue? And the second is, By what means is the muscle enabled to return to a state of functional activity? We know that the mere life of a tissue must be accompanied by certain chemical changes which require (a) a supply of fresh material, and (b) the removal of certain substances which are the outcome of the tissue change.

In the case of muscle, this chemical interchange is constantly but slowly going on between the contractile substance and the blood. When the muscle contracts, much more active and probably different changes go on in the contractile substance, more new material being required, and more effete matter being produced. It is probable that the accumulation of these effete matters is the more important cause of the loss of irritability in a muscle, for a frog's muscle, when quite fatigued, may be rendered active again by washing out its blood vessels with a stream of salt solution of the same density as the serum (.6 per cent. NaCl), and thus removing the injurious "fatigue stuffs," as they have been called. It is found that a very minute quantity of lactic acid injected into the vessels of a muscle destroys its irritability, and brings it to a state resembling intense fatigue. Of the new materials required for the sustentation of muscle irritability, oxygen is among the most important, though its supply is not absolutely necessary for the recuperation of a partially exhausted, isolated frog's muscle.

The slow recovery of a bloodless muscle from fatigue may be explained by supposing time to be necessary for the reconstruction of new contractile material, and probably, also, for a secondary change to take place in the effete materials, by which they become less injurious.

When working actively the muscles require an adequate supply of good arterial blood in order to ward off exhaustion; and, as already explained in speaking of the vasomotor influences, a muscle receives a greater supply of blood when actively contracting than when in the passive state.

The irritability of a muscle and the rate at which it becomes exhausted may be said to depend upon: -

1. The adequacy of its blood supply: the better the supply of new material and the more quickly the injurious effete materials are removed, the more work a muscle can do without becoming exhausted.

2. Temperature has a marked effect on the irritability of muscles, as well as upon the form of this contraction. Low temperatures - approaching 50 C. - diminish the irritability of a muscle, but do not seem to tend toward more rapid exhaustion. High temperatures - approaching 300 C. - increase the irritability, and at the same time rapidly bring about fatigue. At about 350 C. an isolated frog's muscle begins to pass into heat tetanus, and permanently loses its irritability.

3. Functional activity is accompanied by an increased blood supply, and a more perfect nutrition of the muscles, hence activity is advantageous for their growth and power; while, on the other hand, continued and prolonged inactivity causes a lowering of the nutrition and loss of irritability. Thus, when the nerves supplying the voluntary muscles are injured, there is considerable danger of atrophy and tissue degeneration of the muscles; the contractile substance becomes replaced by fat granules. This degeneration also occurs in the stump when a limb is amputated, the distal attachments of the muscles having been cut they cannot act, and after some time they become completely atrophied, so that muscle tissue can hardly be recognized in them.