Muscular Activity

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ARCHIBALD ViviAN Hr, M.A., Sc.D., F.R.S. Professor of Physiology, University College, London a COMPOSED AND PRINTED AT THE Tue Wittrams & Wimx1ns Company Baurimors, Mp., U. 8, A, In November, 1902, Dr. and Mrs. Christian A. Herter, of New York, gave to the Medical School of The Johns Hopkins University the sum of $25,000 “for the formation of a memorial lectureship designed to promote a more intimate knowledge of the researches of foreign investigators in the realm of medical science.’”’ According to the terms of the gift, some eminent worker in Physiology or Pathology is to be asked each year to deliver a lecture at the Johns Hopkins University upon a subject with which he has been identified.

The selection of the lecturer is made by a committee representing the departments of pathology, physiological chemistry, and clinical medicine of The Johns Hopkins University, and if ‘in the judgment of the committee it should ultimately appear desirable to open the proposed lectureship to leaders in medical research in this country there should be no bar in so doing.” The earlier Herter Lectures, 1904 to 1923 inclusive, have appeared in The Bulletin of the Johns Hopkins Hospital.

The publishers plan to issue the lectures in book form. Announcement of titles will be made as each book is issued In the preface to his book “The Respiratory Function of the Blood”, Mr. Joseph Barcroft quite rightly tells us that long ago, by spending his leisure in sailing boats, he learnt what he knows (which is no little) of the way to venture beyond the visible horizon. Now, the practice of running is just as ancient and respectable as that of sailing, and the reader may perhaps see signs of the source of my inspiration, at any rate in the fourth lecture of this series: indeed, to tell the truth, it may well have been my struggles and failures, on track and field, and the stiffness and exhaustion that sometimes befell, which led me to ask many questions which I have attempted to answer here. In that attempt, to continue the analogy, I was given a very long start, for Sir Walter Fletcher was my tutor and counsellor at Cambridge and Sir Walter Fletcher’s chief pride —in spite of all that he has accomplished in physiology and in the organisation of medical research—is that he once ran for two English Universities against two of the United States.

It was no small honour to be invited to give these Herter lectures, to represent the English Universities not against but before those of America. Yet what one remembers after is not so much the honour as the goodwill and understanding, bred by comradeship and friendly rivalry in discovery. May I therefore acknowledge here, not by name for the list would include the whole of the Medical Faculty and many others, the kindness which I received in October, 1924, from my colleagues in Baltimore.

In these lectures I shall deal, not with the whole province of muscular activity, which would require rather a textbook than a series of lectures, but with certain newer aspects of the subject, the mechanical, thermal and chemical, and finally the application to man of the results obtained. In this first lecture I will discuss, not the whole problem of _the mechanical response of muscle, but certain developments of the last few years, starting with the capacity of the muscle to do external mechanical work.

Much investigation has been devoted in the past to the mechanical response and characteristics of muscles. These were the easiest properties of muscles to investigate, and represent the final and important results of their activity. It might have appeared, however, that the subject is by now to some degree worked out and unlikely to yield further results of value. Actually, however, in combination with thermodynamical observations and considerations much information has been derived recently from a study of the mechanical output and behaviour of striated muscles. Indeed, in the last few years the investigation of the connection between rate of shortening, or work done, and heat-production has pointed to new, hitherto unsuspected, mechanisms in muscle, which are of considerable theoretical interest and practical importance.

Let us start by considering the muscle as an elastic body. When a resting muscle is stretched the greater the force used in stretching it, the greater the amount of extension, as in any elastic body: and the relation between extension and force (OA, fig. 1) may be plotted to give what engineers call a stress-strain diagram; from this the work done in stretching, or the work obtainable from to regard the excited muscle as a new elastic body, possessing new elastic properties, and to determine experimentally for it also the relation between length and force exerted at that length. The result gives us what we may regard as a stress-strain diagram for the active muscle, and if we are correct in our hypothesis that the muscle is an elastic body, the work which it can do may be calculated from the area enclosed in the diagram. The work is clearly a function of the size of the muscle, that is, of its length and its thickness, and also of the intrinsic physiological capacity of

Fig. 1. Revation Between TENSION AND EXTENSION IN A RESTING Muscip The full curve OA corresponds to a very slow process of unloading or loading the muscle from or to a given tension, and represents a ‘‘reversible’’ process. The broken curves represent ‘irreversible’? processes carried out more or less rapidly. The curves OBA, OCA and ODA correspond to loading carried out rapidly, the most rapid being OBA, and the least rapid ODA. The curves AB’O, AC’O, AD’O, correspond to unloading carried out rapidly, the first being the most and the last being the least rapid. The potential energy possessed by the stretched muscle corresponds to the area OAa: the work done in stretching it rapidly along (say) the curve OCA corresponds to the area OC'Aa; the work obtained from it on unloading it rapidly corresponds (say) to the area AC’a: the work lost and degenerated into heat irreversibly in the complete cycle corresponds therefore to the area OCAC’.

(Note: The curves are illustrative only and do not represent an actual observation.) (After Hartree and Hill, 1920.) its fibres for exerting a force. The simplest way of regarding the matter is to say that the work should be proportional to the product of the length J of the muscle and the force 7’ which it can exert in an isometric contraction. It is then found that the area of the stress-strain diagram of the active muscle is equal to 71 multiplied by a factor

Fig. 2. Revations Between Maximat TENSION AND LENGTH IN THE PRoLONGED CoNTRACTION OF A FROG’s SARTORIUS Curves I to VIII, all of the same shape, were made at various times (0 to 29 hours) after removal of the muscle from the body. (After Ma- shimo, 1924.) which is usually (in a twitch) about one-sixth. It is greater in a prolonged contraction. The theoretical maximum work of the muscle excited to a twitch—its potential energy—should thus be expressible as 71/6, and if we wish to compare the mechanical with the thermal re- ‘sponse, we should try to relate 71/6 to the heat production. Some years ago I made experiments with the frog’s

sartorius on these lines, and, expressing both potential energy and heat in mechanical units, was astonished to find them to be fairly closely equal. On the elastic hypothesis, therefore, the whole of the initial energy of the muscle was liberated as mechanical potential energy, and might conceivably, under the best reversible conditions, be turned into external work. This fact was the starting point of the investigations which we will now discuss.

In actual practice it appeared that the isolated frog’s muscle, carrying out an ordinary fairly rapid contraction, was unable to do anything like its theoretical maximum Permanent load 5 grams. Galvanometer deflections representing rise of temperature. At the beginning of the left hand curve 155 grams was hung gently on the muscle: the temperature rose. At the beginning of the right hand curve, after the 155 grams had been hanging on the muscle for some time, it was gently removed: the temperature fell rapidly (the reversible thermodynamic effect) and then rose (the irreversible loss of potential energy under viscous forces). Time in secs. shown on the - curves. (After Hartree and Hill, 1920.)

of mechanical work: either the elastic theory was grossly at fault and the excited muscle could not be regarded as a new elastic body, or some factor was disturbing the ready transformation of elastic energy into work. To accept the first alternative would have been a confession of failure, since it would have left us without any working hypothesis at all as to the nature of the muscular response. One looked naturally therefore for factors which might account for the large amount of energy used in an actual shortening. In 1919 Hartree and I came upon certain interesting thermal properties of resting muscles which appeared during passive shortening or lengthening. If an elastic body be

stretched or released it has long been known that certain reversible thermodynamic alterations of temperature result, which were first described by Kelvin. These we found also in our resting muscle. In addition, however, large irreversible productions of heat occur when a muscle is stretched or released. These could be associated only with the frictional transformation of mechanical energy into heat in a viscous system, and they led us to the hypothesis that the loss of energy which we required was due largely to such frictional causes. (See also fig. 1.)

It was possible, moreover, that the conditions of loading the muscle, as originally applied, were not satisfactory, that in shortening the muscle was not given at each length the maximum load which it could overcome. The obvious means of supplying the muscle with a load better adapted to its requirements was to oppose it, not by a constant force but by the inertia of amass. According to Newton’s laws of motion, ‘‘to every action there is an equal and opposite reaction,” so that if a muscle were pulling directly

always be exactly equal to the force which the muscle could exert on it. An inertia is the optimum type of load. We constructed therefore, as we found afterwards Fick had done before us, an inertia lever, a freely suspended - beam bearing balanced masses against which the muscle could pull, and we recorded the amount of work which the muscle did by seeing how far it could raise a rider hanging on the lever. We obtained in this way larger amounts of work than by other mechanical arrangements for loading, but still nowhere near the theoretical maximum unless the inertia of the lever were made very large and the speed of shortening very small. The rate at which a muscle is able to shorten depends upon the inertia of the lever. With a very light one it shortens rapidly and produces a

muscle been similar in its elastic properties to a steel spring, the product }MYV?, that is the kinetic energy produced in the lever, would have been the same whether the lever was light or heavy. Actually with the muscle it was much greater with the heavier lever. The loading conditions were theoretically the optimum imaginable, so that one could only look, for a reduction in the work obtained, to something analogous to viscosity, or friction, hindering the rapid shortening of the muscle fibres. The muscle

Left, inertia lever, with weights W, W, and screw S for adjustment of the centre of gravity on to the line of the knife-edges. Rider and scale for measuring work. Lever L with adjustable stops A, A, for (1) limiting the extent of contraction, and (2) electrical timing of the duration of | shortening. Top, quick-release mechanism, withdrawing the stiff-wire hook H from between the guards G, and so releasing a loop on the fine wire holding the muscle stretched. Right, muscle holder for carrying a pair of sartorius muscles immersed in Ringer’s solution in a Dewar flask. B, B, vulcanite screws for holding acetabulum; E, E, electrodes passing between the muscles. (After Gasser and Hill, 1924.)

was presumably not simply an elastic system but a ‘viscous elastic” system, similar to a thin rubber tube filled with thick treacle, in which the more rapid the shortening the greater would be the amount of mechanical energy dissipated in overcoming the inherent frictional resistance of the body itself. These experiments on the isolated muscle led to an attempt to test the same phenomenon on human muscles. A large and accurately balanced wheel was constructed (fig. 5) against the inertia of which the flexors of the arm could exert a maximal pull. The work done by them was

measured from the angular velocity produced in the wheel, and the speed of shortening was determined by the breaking of two electric contacts. The speed of shortening could be varied by winding the string which pulled the __ wheel round one or other of a set of pulleys of different _ size: on the large pulley the wheel ‘‘felt light,” on the small < pulley it ‘felt heavy.” Expressed more exactly, the “equivalent mass” of the wheel could be varied by varying the diameter of the pulley round which the string was ‘wound. With a large equivalent mass the shortening of the muscles was slow, with a small equivalent mass it

was large, the contraction being maximal in every case. A quick release was arranged by which it was ensured that — the maximum tension of the muscle had been attained before shortening was allowed. It was then found that the work done in a maximal effort of the flexor muscles of the © arm varies inversely with the speed of shortening, being greater at low speeds, less at higher ones—clearly the same Fig. 6. Revation BetwEEN Work Done anv Time OccurPiIEeD IN THE MovEMENT IN THE CaSE OF A MAxIMAL FLEXION OF THE HuMAN ARM

type of relation as we had been led to expect from our experiments on the frog’s sartorius. (See fig. 6.) It was . natural to conclude that this loss of work at the higher speeds was determined by the viscosity of the muscle substance itself, the work lost being turned irreversibly into heat during the change of form of the shortening muscle. shortening, has an important application in connection with human muscular efforts of various kinds carried out at varying speeds. Common sense and every-day experience have led people to adopt certain rates at which ordinary movements are performed: the size of a spade is adjusted to give a certain speed of movement when wielded by an ordinary man: the gears of bicycles and of many kinds of machinery are adjusted to attain an optimal speed. The experiments just described afford a scientific explanation of these facts. If a muscular movement be carried out too quickly very little work will be done by it: con- ‘sequently its efficiency will be low: if it be carried out too

slowly a large amount of work will indeed be , done, but the amount of amount of energy expended ph slo ologically by the muscle in in maintaining its its contraction ee! will be too large, and again the efficiency will be low. te arene maximal efficiency is attained at some intermediate speed, and it is this speed which every-day experience and common sense have led us to adopt in our ordinary working life. The experiments on_man were not conclusive in one direction, since it was possible that the variation of work with speed might be due to some kind of nervous adjustment regulated through the proprioceptive nervous system. A rapid movement of the muscle might stimulate nerve endings in it, or in its tendons and joints, which would

fibres. The quick release of a muscle, for example, might be very gengerolls to_an animal, were the whole of the eberey of the contracting muscles turned into kinetic “energy in the limb; it was possible that a protective reflex maintain the contraction as soon as the latter was no longer needed. The matter could obviously be decided by reany possible reflex mechanism. This was the starting point of the experiments which have been performed poring

An arrangement similar in principle, though different in design, to the inertia wheel was constructed for the sartorius preparation of the frog. (See fig. 4 above.) The necessary range of equivalent masses was provided, by which the speed of shortening of the muscle after a quick release could be adjusted from very rapid to very slow. It Fie. 7. RELATION BETWEEN Work Done oN INERTIA LEVER, AND SPEED or SHORTENING Frogs’ sartorius muscles stimulated directly and isometrically with maximal tetanus, and released to work on lever only after maximal tension attained. Speed in arbitrary units, a/t, where a = amount and ¢ = time of shortening. (After Gasser and Hill, 1924.)

fibre itself and not connected in any way with the nervous. system. If the work varies with speed so also must the force exerted by the muscle during any given element of its shortening: hence the force exerted by the muscle must decrease as the speed of shortening increases. This was the starting point of the next stage. It is possible in an isolated muscle with parallel fibres to connect one end A to a tension lever, and so to measure the force which it exerts, while subjecting the other end B

to any desired mechanical conditions, such, for example, as allowing it to shorten, or causing it to lengthen, at any desired speed. (See fig. 8.) The muscle is so short and light that the time taken in transmitting to A any change in tension produced by the events at B is very small. Moreover, the absolute velocity of movement in such a small muscle is so low that no appreciable amount of energy Fic. 8. Isometric tension recorder. With projection P for carrying short bamboo pointer, and screw S for keeping spring taut; adjustable jaws for regulating amount of movement of knot K; A, A, slit guides for steel wire connecting muscle to quick release mechanism.

Fic. 9. Effect of quick release on tension recorded in maximal isometric tetanus. Frog’s sartorius. Right, amount of release allowed, millimeters. Bottom record, release of resting muscle. Read from left toright. (After Gasser and Hill, 1924.) appears in the muscle as kinetic energy, even though the duration of its shortening be very small. Hence, even relatively sudden changes at B do not cause bad mechanical oscillations at A, provided that the tension lever at A possesses a high natural frequency of vibration.

The first experiments we made were as follows. A muscle was stimulated with a tetanising current and its tension recorded. It was then allowed suddenly to shorten freely a given small distance; it might have been expected that the tension would merely fall from that corresponding to Fie. 10. Diagram Coprnp rrom Recorps or Errect or Quick RELEASE Note that the effect of temperature on the curve of the initial development of tension is the same as on that of the redevelopment after release. (After Gasser and Hill, 1924.)