with Nigetiet and Hefner'). This seems to be dependent in part at least on the diminution in the quantity of glycogen, and increase in the amount of sugar. With regard to the relative amount of creatine and creatinine in resting and contracting muscle, various conflicting statements have been made (see p. 421); but the balance of evidence is very much in favour of the view that on contraction creatine is transformed into creatinine.

4. Production of reducing substances.-Resting muscle oxidises pyrogallic acid, tetanised muscle does not. A solution of nitrites passed through contracting muscle is changed into nitrates, and the colour of solutions of indigo-sulphate is altered in the same way as it is by reducing substances (Grützner, Gschleidlen3). A. Schmidt4 arrived at similar conclusions from the examination of the venous blood of tetanised muscle, but what the reducing substances are that are produced is quite unknown.

5. Changes in the salts.-Weyl and Seitler5 have pointed out that in the earlier stages of muscular activity the acid reaction may be partially due to acid potassium phosphate produced from the alkaline phosphate, by the development of new phosphoric acid from organic phosphorised compounds like lecithin and nuclein in the muscle.

6. Changes in the gases. These may be briefly summarised by saying that on contraction, as on the occurrence of rigor mortis, the amount of carbonic acid given off is increased. The amount of oxygen absorbed is also increased, but not in proportion; in other words, the Carbonic acid exhaled fraction is increased.

Oxygen absorbed

Fatigue of muscle.--The way in which repeated contraction causes what is known as fatigue is very uncertain. It may be due to the accumulation of the products of combustion, or to a defect of oxygen, and probably of other constituents of a normal muscle; or it may be due to a combination of these two sets of causes.

With regard to the former, the accumulation of products of combustion, Ranke" pointed out the depressing effect on muscular irrita

1 Pflüger's Archiv, iii. 574. 3 Gschleidlen, Ibid. viii. 506. 5 Zeit. physiol. Chem. vi. 557. J. Ranke, Tetanus, p. 350. The increased acidity of fatigued muscles has since been noted by numerous observers; among the more recent researches on the subject may be mentioned: Warren (Pflüger's Archiv, xxiv. 391), who finds that, though the acidity is increased, the number of acid molecules in the muscle are diminished; this is explained by supposing that in resting muscle the anhydride, and in contracting muscle the free acid is present, which latter combines with twice the amount of base as the anhydride; Moleschott and Battistini (Arch. Italiennes, viii. 90) used phenol phthalein and

2 Gritzner, Ibid. vii. 255.

4 Sitzungsberichte der k. k. Akad. Wien, vol. xx.

F F

bility produced by all acids, carbonic acid, and lactic acid, among others. Renewal of the blood stream through exhausted muscles causes them to revive; this may be due (1) to the removal of the acids and other products of contraction; (2) to the fresh supply of oxygen; or (3) more probably still to both these factors combined. Mosso considers that the poison which causes the symptoms of exhaustion is probably not carbonic acid, but a substance produced in smail quantities of an alkaloidal nature.

Hermann's theory of muscular contraction.2-The fact that no oxygen is obtainable from muscle suggested to Hermann the theory that the formation of carbonic anhydride on contraction is not simply due to oxidation, but rather to the decomposition of a complex substance with the formation of certain simpler products of which carbonic anhydride is one. This complex nitrogenous substance he calls inogen, and the products of its decomposition he considers to be carbonic anhydride, sarcolactic acid, and myosin. The first passes into the blood stream, and the other two apparently help in forming again the original inogen. Hermann considers that the same decomposition occurs in rigor mortis, only to a much greater extent; contraction is thus a condition of partial death, and this view is supported not only from the chemical standpoint (the formation of acid), but also from the electrical point of view, both dead and contracted muscle being negative potash as indicator; A. Monari (Chem. Centralbl. 1887, p. 1360) considers that the increased acidity causes a partial conversion of creatine into creatinine. Marcuse (Pflüger's Archiv, xxxix. 425) considers that whereas the lactic acid formed during rigor mortis is not formed from glycogen (p. 409), yet that formed during contraction probably is, as the glycogen diminishes on contraction. But, as Molinari points out (Chem. Centralbl. 1889. vol. ii. p. 372), this is by no means conclusive, as the diminution of glycogen on contrac tion is probably due to its conversion into sugar. Marcuse also finds that the urine of frogs after extirpation of the liver contains lactic acid if the muscles be tetanised. Under normal circumstances the liver destroys lactic acid (Minkowski).

1 Report of Internat. Med. Congress, Berlin, 1890.

For an account of the various theories that were held regarding muscular contraction previous to Hermann, the reader is referred to Gamgee's Physiol. Chem. pp. 406–419. John Mayow (1668-1674), who really discovered oxygen, spoke of it as nitro-aërial particles, and the combination of these with salino-sulphureous or combustible particles in the muscle caused heat, and an effervescence which produced muscular contraction. Stahl introduced the doctrine of an immaterial anima with unlimited spontaneous power over matter, including the muscles; this under the names of sentient principle (Whytt) and vital force (Hunter) survived until Liebig's time. The rediscovery of oxygen and of its importance to animal life was the occasion of the production of several theories as to the part it played in causing contraction of muscles; and the theory of the conservation of energy helped in the understanding of the relations of the physical and chemical changes which occur in muscle (Mayer, Heidenhain). M. Traube pointed out fully that no albuminous substance is used up on contraction, and Matteucci concluded that the oxygen which forms the carbonic acid in muscular respiration is derived, not from the air or blood directly, but from that which is present in the muscle itself in a state of loose chemical combination.

to living muscle at rest. The question arises, is there any evidence of the formation of a muscle-clot (myosin) during contraction? It is difficult to prove or disprove such a contention, as Hermann supposes that the process of clotting is not so complete as in rigor mortis, but that it only goes as far as the viscous or gelatinous stage, and such a change would not be apparent to the microscope.

I have in the earlier parts of this chapter pointed out that myosinogen and myosin are easily converted the one into the other (p. 408), and a suggestion that might arise is this-if myosin can be made to clot and unclot so easily out of the body, is it not possible that a similar condition exists in the body? The experiments certainly show that myosin and myosinogen are very unstable substances; and this is supported by the fact that myosinogen acts like fibrin-ferment in hastening blood-coagulation; it is therefore quite possible that during contraction the proteid myosinogen may undergo certain intramolecular rearrangements, perhaps of the same nature as those which occur to a far greater degree on the death of the muscle, in each case leading to a liberation of acid. But with regard to the formation of a clot during contraction, there is one physical change which in particular shows there is a great distinction between dead muscle and contracted living muscle. This change is the alteration in the extensibility of the muscle, which in rigor mortis is diminished and on contraction is increased. In other words, rigor makes the muscle less extensible, because it becomes more solid owing to the formation of the myosin clot, but, during the contraction of a living muscle, it becomes in a sense more liquid, as is shown by its increased extensibility, and this is certainly against the theory of the formation of a solid clot during contraction.

.

Bernstein's theory of muscular contraction.'—The following admirable summary of Bernstein's views is taken from Dr. Burdon-Sanderson's address to the British Association, 1889.2 The contraction which a muscle undergoes when stimulated has its seat, not in the system of inotagmata (see p. 189, or disdiaclasts, see p. 403), but in the interstitial material that surrounds it, and consists in the migration of that labile material from pole to equator, this being synchronous with explosive chemical change, sudden disengagement of heat, and change in the electrical state of the living substance. The chemical changes that take place and lead to the production of heat are indices of oxidation. There must be in the sphere of each tagma an accumulation of oxygen and oxidisable material, and concomitantly with or antecedently to the 1 Bernstein, Neue Theorie d. Erregungsvorgänge u. electr. Erschein. an der Nervenund Muskelfasern,' Unters. aus dem. Physiol. Institut, Halle, 1888.

migration of liquid from pole to equator these must come into encounter. Let us suppose that a soluble carbohydrate is the oxidisable material, and that this is accumulated equatorially, and oxygen at the poles; consequently, between equator and poles, water and carbonic acid, the products of the explosion are set free. That the process is really of this nature is the conclusion to which an elaborate study of the electrical phenomena which accompany it has led Professor Bernstein. His view of the molecular structure of muscular protoplasm is in entire accordance with the theory of Pflüger (see p. 115), and with Engelmann's scheme of muscular structure (see p. 189), with this addition, that each inotagma is electrically polarised when in a state of rest, depolarised at the moment of excitation or stimulation, and that the axes of the tagmata are so directed that they are always parallel to the surface of the fibre and consequently have their positive sides exposed. In this amended form the theory admits of being harmonised with the fundamental facts of muscle-electricity, namely, that cut surfaces are negative to sound surfaces, and excited parts to inactive, provided that the direction of the hypothetical polarisation is from equator to pole, i.e. that in the resting state the poles of each tagma are charged with negative ions, the equator with positive, and consequently that the direction of the discharge in the catalyte (or oxidisable material) at the moment that the polarisation disappears is from pole to equator. The same theory, moreover, enables us to express more consistently the accepted explanations of many collateral phenomena, particularly those of electrotonus. Sufficient has, however, been said to show that it is not impossible to regard the three phenomena (chemical explosion, sudden electrical change, and change of form) as all manifestations of one and the same process-as products of the same mechanism.'

Effects of Muscular Contraction on the Urine

The effects of muscular contraction on the urine are exceedingly slight; it is only after prolonged and violent muscular exercise that any change can be perceived at all, and even then it is out of all proportion to the amount of contraction. This is in marked contrast to the very great effect that muscular contraction has on the respiratory excretion (see pp. 374, 427). It is in the urine that urea, uric acid, and other products of nitrogenous metabolism or combustion leave the body; and, as we have already seen, there is very little change in the chief nitrogenous constituents of muscle, the proteids, on contraction; but the substances which undergo an accelerated chemical change or combustion on contraction are the non-nitrogenous constituents.

1

Voit investigated the question in a dog; the animal either went without food or was put on a carefully regulated, fixed diet; the work done was the turning of a treadwheel, and the urine was carefully collected. A very slight increase in the amount of urea excreted was noted after work, and it was not at all proportional to the amount of work done.

The experiments made on human beings fully corroborate Voit's experiments. Of these the experiment of Fick and Wislicenus 2 in the ascent of the Faulhorn has become classical. The following are the chief of the facts they ascertained.

For seventeen hours before the ascent, during the ascent, and for some hours afterwards no nitrogenous food was taken. The urine was carefully collected and the urea determined in it by Neubauer's method for the periods before, during, and after the exertion. The work done was also estimated. The total nitrogen was determined by combustion with soda-lime. The height of the mountain is 1,956 metres. Fick weighed 66 kilograms, and Wislicenus 76 kilograms. The work done by Fick in raising his body to the top of the mountain =66 × 1956=129,096 kilogram-metres; similarly, the work done by Wislicenus was 148,656 kilogram-metres. This does not take into account any other muscular work, such as the movements of respiration, circulation, movements of the arms and trunk muscles, &c. The nitrogen in the urine (the small quantity which escaped by the sweat and fæces being disregarded) during the work and for six hours after was, in the case of Fick, 5.7 grammes, which corresponds to that obtained from 37·1 grammes of proteid; and, in the case of Wislicenus, to 5.5 grammes, which corresponds to that obtained from the decomposition of 37 grammes of proteid.

Frankland has shown that from the burning of 1 gramme of lean beef a quantity of heat is formed which corresponds to 2161 kilogrammetres, so that the amount of work obtainable from 37·1 grammes of proteid in Fick's case was 37·1 x2161-80,324 kilogram-metres; in Wislicenus' case 37 × 2161-79,956 kilogram-metres-that is to say, much less than the work actually done. The disproportion is really greater, because the physiological heat-value of proteid is less than its physical heat-value; proteids do not in the body undergo complete combustion; the physiological heat-value of proteid is its physical heatvalue minus the heat-value of urea.

This experiment clearly showed that proteid metabolism will not account for all the work done; it however does not settle the question 1 Untersuch. ü. d. Einfluss des Kochsalzes, des Kaffees und der Muskelbewegungen auf den Stoffwechsel, Munich, 1860.

2 Vierteljahresschrift d. naturf. Gesellsch. in Zürich, x. 1865. London, Edin. and Dublin Phil. Magazine, series 4, vol. xxxi. p. 485.

5 Frankland, Lond. Edin. and Dublin Philos. Mag. series 4, vol. xxxii. p. 187.