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INTRODUCTION. The cardiac muscle of cold blooded animals offers an exe cellent material for the study of the mechanism of contraction, It has certain advantages over skeletal muscle, and although differing in some respects from that tissue; it may be assumed a priorij that what is learned from one may be ultimately used in the study of the other, The most important advantage of card- iac over skeletal muscle is its complete response ‘to a stimulus of whatever strength; the all or none principle of Bowditch, since all the musdle fibers are caused to react by any adequate timate, results are not confused by the action of only a part of the fibers, as in skeletal muscle, Thus we may assume that in és muscle if a contraction is produced at all it represents the absolute capability of the muscle under the existing conditions. A second advantage is that the processes are slower in the case of heart muscle, and may be more readily analyzed, Furthermore, fatigue develops much more slowly, and approximately constant con- ditions may thus be maintained for long periods of time, A level of contraction may be maintained for long periods, in which all contraptions are equal when the rate of beat is constant, Smith (1926) has shown that in turtle atria the amplitude of contraction alters with the rate of the contraction, An optimal frequency exists at which the contractions are maximal. If this frequency is increased or decreased from the optimum, the amplidude of the contractions decrease to a new level, Redfield and Edsall (unpublished manuscript) suggest that when a heart muscle is contracting rhythmically and constantly, it “l= may be considered to be operating at a fatigue level at which the anaerobic production of lactic acid just balances its oxid- ative removal. This is in accordance with present day concept- ions of the chemistry of muscle contraction (Meyerhof 1924. Chap=- ter IV, Hill 1926). The work of Redfield and Medearis (1926) indicates that the tension per unit cross section developed at any beat is proportionaly to the lactic acid content of the muscle. This indicates that lactic acid or hydrogen ion concentration may be the limiting factor in tensim production, and lends support te the above suggestion. In order to harmonize this idea with Smith's results, it is necessary to assume that the rate of resynthesis of lactic acid to its precursor (oxidative recovery) is altered with the rate of stimulation. Obviously, the product- ion of lactic acid will be slower with a slow rate of stimulation, and the oxidative recovery must be much reduced in order that suf- ficient lactic acid can accumulate to reduce the amplitude of the contraction below the optimum, Meyerhof et. al. (1925) presents evidence that the accumulation of lactate may set the pace for this resynthesis to the percursor, which accords with this cone ception. However, evidence will be brought forward in the follow- ing experiments which may indicate that another factor is concerned in establishment of the amplitude of the contractions at a given fatigue level, It is commonly known that, in cardiac muscle, a contraction is followed by an absolute refractory period during which it is impossible to produce a second contraction with any stimulus, no matter of what strength. This was named by lMarey (1877, 1879) the "refractory phase." This is followed by & period during which Be. both the excitability and contractility of the muscle are reduced below the normal. The return of excitability has been studied by numerous authors, including Trendelenburg (1903, 1911), Adrian (1920) and Wastl (1922). The return of contractility has been studied quantitatively, only by Trendelenburg (1911) and Adrian (1920). Adrian described a gradual return of contractility following a smooth curve, and under certain conditions exhibiting a supernormal phase, Consideration of the above phenomena suggested that a study of the return of contractility in heart muscles driven at regular frequencies might prove valuable. The experiments described be- low have resulted. II. METHOD. The muscle strips used in these experiments were cut from the apical border of turtle ventricles. These were suspended in the chamber diagramed in fig. 1, by means of stout thread tied around the two ends of the strip. Provision was made for the rapid removal and renewal of solution in the chamber at any time, and for passing oxygen through the selution. It was found that the ventricular strips always developed more or less regular beats in ordinary "Ringer's" solution (see Lingle 1905). Therefore a solution containing magnesium chloride similar to that described by Smith (1926) was used. Its compos=- ition was as follows: The Py of thi® solution was always between 8 and 9. In such a solution the strips remsined quiescent or showed only rare con- tractions, while the contractility was not appreciably reduced in the course of several hours, The tension produced by the muscle was recorded on a smoked drum by means of a tension lever similar to that described by Redfield and Medearis (1926). The blade of a jewelers hackesaw, supported in its own frame, served as the torsion spring. A very light clamp was attached firmly at the mid point of the spring. Projecting from the clamp, horizontally and perpendicular to the spring, a sut steel wire about 1 cm. long served for the attach- ment of the muscle. This wire was bent into a small V with its apex just 1 cm. from the saw blade and directed downward. The thread from the muscle was attached at this peint., On the opposite side of the saw blade, the clamp supported a short aluminum wire, horizontally and perpendicular to the blade. A very light hollow straw was fitted over this wire to serve as a writing lever. The writing point used was constructed after the method of Bayliss, described by Frank (1911). This consists of a celluloid point attached to a small square of heavy paper by a strip of goldbeater membrane. The celluloid point moves freely in a plane perpendicular to the surface of the smoked paper, but is quite rigid in a plane tangential to it. Thus a minimum of friction is obtained with a maximum of accuracy. The distance from the spring to the writing point was 17.7 cm., thus magnifying the shortening of the muscle 17,7 times. With a muscle 3 cm. long producing a record 3 cm. in amplitude, this represents a departure from" isometricity” of less than 6%. The example cited, represents a maximum deviation in the a4 “He experiments performed, most of the contractions recorded, approach- ing within less than 5% of “isometricity". The natural period of vibration of the lever was .07 sees. 3ince the contraction of the turtle ventricle muscle consufies over 2 seconds, the period of the lever ig sufficiently high to eliminate any errors due to fling. 4 signal magnet, marking the time of stimulation and a Jaquet chronometer marking seconds or fifths of seconds, were also mounted to write on the drum. These together with the tension lever, were supported on a Ludwig adjustable stand. An extra vertical rod was fastened to the rotating plate at the base of the stand, and the muscle chamber clamped to this. Thus the entire apparatus could be rotated horizontally to approach the smoked drum, the adjustable stop at the top of the Ludwig stand being set so that the pressure of the writing points against the smoked paper could be made constant in successive records. Also, the tension lever could be raised or lowered with regard to the muscle chamber by means of the verticaid adjustment of the stand. This allowed for the adjustment of the initial tension on the muscle. The signal lever and chronometer maintained the same position relative to the lever during such adjustment, and it was thus possible to use the signal magnet as a reference point in the calibration of the lever. The lower end of the muscle was attached by means of a stout thread to a hook at the end of a glass tube extending down from the roof of the chamber (see fig. 1). The glass tube was fitted over an aluminum rod fastened securely in the roof of the chamber. The tube fitted closely over the rod and was firmly attached to it by means of de Kotinsky wax. The rod could be sk 8 fe Mbrosiue orem tad Deoniest um Dow dpold To RT PIsC west FL wa ad? 284¢ om Jes bent slightly to adjust the position of the hook in the chamber, but the scheme was sufficiently rigid to serve as a support for the muscle. Calibration of the tension lever was accomplished as follows; A small paper pan of negligible weight was constructed so that it could be suspended by threads from the same point of attachment on the lever as was used for the muscle. Weights were placed on the pan, and the position of the lever corresponding to each load was marked on the drum by rotating it a few millimeters. The signal magnet served as a base line.from which the distances corresponding to each load were measured. A calibration curve was prepared from these measurements and the records of muscular contraction analyzed in terms of this curve. All measurements of these records were made to 0.1 mm. by means of vernier calipers. Since errors corresponding to 0.5 gnm.. occured occasionally in the calibration records, accuracy beyend this point was not considered. Since the average tension product- ion in the experiments was above 20 gms. the greatest error is on the average 2.5%. The maximum error im any experiment is not above 5.0%. Rhythmical electrical stimulation was provided by a rotary contact maker, operating a Porter inductorium through a relay. The relay assured uniformity in stimulation. One disk of the contact maker provided for shorting out of the "make" shocks so that only single brea stimuli were used. Extra stimuli were sometimes provided by the operation of a telegraph key parallel to the contact maker in the relay circuit of the inductorium. In other cases, where exactly reproduceable intervals were required, one of three extra disks on the contact maker was used. These disks carried different numbers of contacts, and could be adjusted for various desired intervals after the rhythmical stimuli. An extra brush was constructed, which could be readily adjusted to any one of these disks, and was counected in parallel with the disk making the rhythmical stimuli. The stimuli were carried to the muscle by two fine platinum wire electrodes. One of these was attached to a binding post in the roof of the chamber. The other wes sealed into the glass tube supporting the muscle, 2 mercury contact being provided from which a wire was lead out through the tube, The free ends of the ‘platinum wires were pushed between the fibers of the muscle, one near each end, These wires were very flexible, and their tension on the muscle was constant and negligible. III. RECOVERY AFTER CONTRACTION, THE EFFECT OF CONTRACTION ON THE TENSION PRODUCED IN SUCCELDING CONTRACTIONS. Experimental Results. In these experiments, the muscle was stime ulated at regular, equal intervals; and allowed to reach a level of szontraction (fatigue level). The interval used in establishing this level for any given series of determinations will be designat- ed as the basic interval for that series, After any given con- traction this interval was altered by interposing an extra stimulus before the basic interval had transpired, or by omitting one or more of the regular stimuli. For convenience in description, the contraction immediately preceeding such an alteration of interval will be designated as contraction.l. Those immediately following will be numbered successively 2 and 3. Fig. 2 is a schematic wl diagram explaining this numeration. The graph shown in fig. 3 was obtained from a series of such determinations on a single muscle. The interval between contract ions 1 and 3 has been kept constant in this series. The curve representing contraction 2 indicates the progress of recovery of contractility following contraction at the basic interval of stimulation. The figure shows that if contraction 2 falls carly (1.5 to 3. sees.) after 1, contraction 3 is increased above the normal at the basic rhythm as represented by contraction 1. Since the interval between 1 and 3 is kept equal to the basic interval, as the interval betwen 1 and 2 is varied that between Z and 3 also varies in an inverse manner. Therefore, since the interval be- tween 2 and 3 is sctually less than the basic interval, the Fate of recovery of contractility must be greatly increased following contraction 2. Im this figure, the curve representing centraction 3, falls below the normal level. This is obviously due to the decrease of the interval between 2 and 3 so that 3 falls within the relative refractory period of 2, Fig. 4 is the kymograph record of a set of such contractions, This record shows that the contractions following 3 become progress- ively smaller until, after a few beats, they again reach the basic level, This temporary alteration in cgmtractility makes it nec- essary after each determination to stimulate at the basic interval for several beats before producing snother slteration of interval. By doing this, each determination follows a period of contracting at the basic interval and the results are comparable. Big. 5 represents a series of determinations in which the interval between contractions 2 and 3 has been maintained constant and equal to the basic interval. Under these conditions, the PLEO Jase «Dw magnitude of contraction 3 may be taken as a measure of the rate of recovery of contractility. From this figure it will be seen that the rate of recovery is greatly increased when contraction 2 occurs within a short interval (1.5 sees.) after 1, but falls rapidly as this interval is increased. Obviously contraction 3 becomes equal te 1 and 2, under the conditions of this series, when the interval between 1 and 2 is the same as the basic inter val. As the interval between 1 and 2 is increased beyond this point, both contractions 2 and 3 are increased above 1, contracte ion Z being always greater than 3. Both figures 3 and 4 are typical examples of numerous experiments performed on separate muscles under similar conditions. Fig. 6 represents an experiment in which the interval be- tween 1 and 3 has been maintained constant (1.6 secs.) while the interval between 2 and 3 has been varied. Curve III represents contraction 3 in this series, For comparison, a curve obtained by varying the interval between 1 and 2 has been included on the same figure. This curve was obtained from the same muscle at the same basic interval. Curve II represents contraction 2 in this series. average nerasl. Curve III represents the recovery following a contraction 1.6 secs. after a basic contraction, while curve II represents the recovery after a basic contraction. It will be noted that these curves are of the same type but differ quanti- tatively throughout. Curve III increases uniformly at a more rapid rate than curve II, From the above experiments it seems justifiable to assume that the rate of recovery is markedly modified with the interval between stimuli, Fig. 4 indicates that the alteration in contractility is very transitory in nature. Fig. 7 is a kymograph record of a series of contractiona in which after a period of contraction at a basic rhythm (interval 8.5 secs.), extra stimuli were interposed at short intervals (1.9 sees.) after the basic contractions. The height of the basic contractions is seen to follow a treppe; ine creasing to a new level which is md&intained. When the extra stimuli are removed, these contractions are seen te fall rapidly to the eriginal level. This is the case even when the extra cone tractions are maintained for a long period of time. From such evidence we may infer that the alteration of the rate of :Cecovery is not due to the altered concentration of any substance which cannot be rapidly removed. The rate of the recovery process séems to be very flexible and readily altered with the conditions of contraction. Discussion. If the curve in fig. 5 is carefully examined, it appears that the amplitude of contraction 2 varies as a function of the time interval between contractions l and 2, Thus; as ft where a represents the magnitude of contraction 2, and t the time interval between 1 and 2. It appears also that the rate of recovery following contract- ion 2 as measured by contraction 3, varies roughly as the reciprocal of the interval between 1 and 2 when this is less than the basic iy re Fapquiioly interval, This velocity reaches its minimum value at the basic interval, but as the interval is prolonged beyond this point, in appears to vary alse with the amplitude of contraction 2. It is thus possible that the velocity varies as a combined function of the amplitude of the precegding contraction, and the reciprocal of the time interval between the two precegding contractions. This may be expressed as: a ves where v is the velocity of recovery following contraction 2. but: =Ft 5 i S.v=bE This becomes a re complicated relationship which, howe ever, is probably susceptible to mathematical analysis. Without further and more precise data, however, it does not seem justifi- able to continue this analysis. It is hopedthat this may be possible at 2 future date, with the accumulation of further experi- mental data. Inspection of curves of the type of fig. 5 indicates that some such relationship exists. If we assume that the velocity v, at any given time, is dependent on the quantity of a substance V : which is present, we may write: V=¢3% Let us assume that V is a substance produced at each con= traction, in proportion to the magnitude thereof; but removed thereafter, very rapidly at first and approaching assymptotically i Sl ERR Lh Ss to zero, or a constant quantity. In a series of contractions at a basic interval it follows on this assumption, that after equilibrium 1s estabitehod, the quantity of V at the beginning of any contraction is the same. This follows, since each contraction is of the same amplitude and the interval between them is the same. We may call this quantity V, . This should obviously vary with oe the besiec interval used. When contraction 2 falls within the : basic interval after 1, s gusntity of V greater them V, is still present, to which is added that quantity produced by contraction Sola 2, Thus the velocity of recovery is greater than is normal fer the given basic intervel. "hen the interval between 1 and 2 is prolonged beyond the basic interval the quantity of V is reduced Yalow Vge However, the quantity of V added by contraction 2 is proportional to its amplitude and greater than that produced by a contraction at the basie interval. Thus the velocity is again increased above the normai. Such zn explanation fits at lesst qualitatively with the curves in fig. 5; and the sbove mathematical expressions. This explanation alse fits well with the observed conditions after periods of rest following periods of stimulation. Under these conditions, the muscle always responds to the first stimulus by | a large contraction followed by a relatively small one. The follow- x ing few contractions may be progressively smaller, but will agsin increase in size in a long treppe. Such a series is shown in fig. 8. This may be readily explained in terms of the above hypothesis as follows: During the period of rest, recovery has proceeded very nearly to the maximum, accounting for the large first contract- ion. The quantity of V is greatly reduced however, accounting for the low rate of recovery following this contraction, and the smaller Such an explanation can only be offered as a working hype- thesis at this time with the hope that it may be developed and tested in the future, IV. THE SO CALLED SUPERNORMAL PHASE OF CONTRACTILITY AND EXCITABILITY. Adrian (1920) deseribes a supernormal phase of contractility in frogs' muscle perfused with Ringer's solution buffered te Py 6.4 to 6.6. This phase of hypercontractility occurs, according to his data, immediately following the relative refractory period, rises to a maximum and falls again slowly toward the normal level, He states that no such supernormal phase occurs in alkaline sole utions (above Py 8) but that under such conditions the contract ility does not rise above the normal. Neither of these events were observed in any of the experi- ments performed by the present author. All of the latter experi- ments were carried on in alkaline solutions (Py between 8 and 9) but in all cases, the recovery continued to increase above the normal for long periods. Sometimes a decrease occured, but only after intervals of five minutes or more. The results obtained with the turtle ventricle need not of necessity hold for the ventricular muscle of the freg. If the same phenomena occur in both cases, however, Adrian's results may possibly be explained in terms of the technique he employed. In his experiments, no fatigue level was established between determinations. The ventricle was rendered quiescent by ligation of the heart at the auriculo--ventricular junction, and paired stimuli immediately ‘applied. The interval between the members of the pairs were accurately measured, but no uniform interval was employed between the pairs, which fell comparitively close together. If in frog ventricles, the magnitude of contraction is influenced by the interval between previous contractions, as in the case of the turtle, Adrian's results may have been confused by this phenom- enon which he did not recognize. : According to the experiments performed by the present author, a supernormal phase may occur, but only when the interval between contractions is prolonged beyond the basic interval at which the heart has been contracting. A supernormal recovery may be induced, however, by an altered interval between precefding contractions. Adrian also reports a supernormal phase, in the excitability of cardiac muscle and of nerve, when perfused with acid solutions, Wastl (1922) alse reports a supernormal phase in apex preparations of frog ventricles. Her preparatiohs were not perfused so that we ean judge nothing as to the reaction of the tissues which she used, Her studies were only qualitative in scope. It 1s not necessarily true that excitability follows the same processes as contractility in heart muscle, or that these pro- cesses are paralleled by the excitability of nerve tissue. However, Adrian's results are similar for the three phenomena. If the pro- cesses are related, his experiments on excitability are subject te = the same possible errors suggested above in the case of contract- ility. Miss Abbott and Miss Kilgariff, working With the present ; author, have demonstrated that the absolute refractory period may 7 be shortened for the contraction, following contraction 2 when the latter falls early after 1. This indicates that the recovery of excitability has been accelerated in the same manner as the recov- ery of contractility under the same conditions, and indicates that the processes may be parallel. VY. THE TREPPE PHENOMENON. Mines (1913) has suggested that the treppe phenomenon, in beth cardiac and skeletal muscle, may be explained as due to increased contractility caused by an increase in hydrogen ions. The increased hydrogen ion concentration is supposed to occur in some localized ares of the muscle fiber due to the production of lactic acid at the time of contraction. After a certain concen- tration occurs, the contractility has reached its optimum and treppe ends. Both Lee (1907) and Robertson (1908) had previously suggested that the treppe in skeletal muscle is caused by increased acidity due to the accumulation of carbon dioxide. Adrian (1920) eriticizes Mines hypothesis and is apparently of the opinion that treppe is due to succeeding contractions falling in the “super- normal phase”, He does not suggest a mechanism for the limiting of the treppe; however. The recent work of Smith (1926) shows that any explanation of the treppe in heart muscle on the basid@ of the direct effect of hydrogen ion concentration or lactic acid per se is not tenable. He has shown that changing the rate of stimulation of denoded turtle atria may cause either a treppe or an "inverted" treppe. Also, either of these phenomena may occur after short periods of rest, depending on the rate of stimulation before and after the rest period, These phenomena, which it seems difficult to distinguish from the classical treppe, occur in oxygen lack (when lactic acid is known to be increased), in solutions saturated with oxygen, or under high or low concentrations of carbon dioxide. Experiments by the present author have confirmed these observations in the case of turtle ventricles. Fig. © shows typical examples. This seems to indicate that neither ladtic acid per se or hydrogen ion can be the determining factor in producing treppe, since the phenome enon takes place when these substances are present in widely varying concentrations. Smith states however, "The phenomenem do suggest that there is some reactant in the muscle cell on the concentration of which perhaps in some localized region, the development of tension is ultimately dependent; and that the concentration of this reactant is affected by the act of contraction itself," It is obvious that the extent of contraction depénds upon the rate of recovery after a stimulus and the interval between the stimuli. Therefore, in order to accord with the results and hypothesis described above (section III), we may modify Smith's statement to read; there is eome reactant ---- upon the concen- tration of which the rate of recovery depends. With such a state- ment we may account for the phenomenon of treppe as a period during which the recovery rate is being gradually altered to accomodate to a new interval between stimuli. According te the hypothesis suggested in section III, this represents the establish- ment of an equilibrium value for VY. Another factor may enter inte this equilibrium. The suggest= ion of Redfield and Edsall (unpublished manuscript) that a fatigue level is established in a rhythmically contracting muscle, at which the anaerobic production of lactic acid just balances its removal in oxidative recovery, must be considered, As indicated above “Ale = = (section I), an increased production of lactic acid may be accompanied by increased oxidative recovery (lMeyerhof et.al. 1925). Since lactic acid may be one limiting factor to contractility, the adjustment of this balance must also be of importance in the pro duction of treppe. It is impossible to determine, at present, whether this laetic acid balance is not intimately connected with recovery rate deseribed in this paper, but it is hoped that further investigation may help to elucidate this. Vii. SIRBRIARY. The amplitude of contraction in heart muscle is dependent upon the rate of recovery and the interval between contractions. The rate of recovery is altered by alteration of the interval between precefding stimuli. The velocity of the recovery process apparently is a com- bined function of the amplitude of the precefding contraction and the reciprocal of the interval between the two precefiding contract- ions. An hypothesis is offered to explain the mechanism of this relationship. The transient "supernormal® phase described by Adrian for frogs ventricle in acid solutions,is not observed in turtle ventricle. The alteration of the rate of recovery from one condition of stimulation, to meet another, may be one factor at least in the pro- duction of the treppe phenomenon, and the establishment of the mage nitude of contraction at a fatigue level. VII. ACKNOWLEDGEMENTS. The author is much indebted to Prof. A. C. Redfield of Harvard ledical School, who allowed him to use apparatus and materials for preliminary experiments, 23 well as unpublished manuscripts. It is a pleasure to acknowledge the kind advice of Prof. S. S. lMexwell, whose patience and encouragement have made the present work possible. Thanks are due also to the other members of the sub-committee, Profs. T. C. Burnett, J. PF, Daniel, W. J. Kerr, C. A. Kofoid, and C. L. Be Schmidt, for like kindness and patience. VIII. LITERATURE CITED. {The following articles contain general references on this subject.) Adrian; E. D. 1920. The recovery process of excitable tissues. Journ. Physiol. 54, 1, Frank, Qs 1911. Handbuch der Physiologischen methodik. Tifgerstedt. Vol. 1, part 4, p. 24. (Leipsig, Hirzell.) Hill, As. Ve ; 1926. Muscular Activity. (Baltimore, Williams and Wilkins.) Lee, F. S. J 1907. The cause of Treppe. /Am.J. Physiol. as, 267. Ligdle, D. T. ; 1905. Restorers of the cardiac rhythm. Am. J. Physiol. 14, 433. Harey, I. p 1877. RAicherches sur les excitations électriques du coeur. Journ de 1l'Anat. et de la Physiol. 13, 60. Marey, M. : _ 1879. Sur 1l'effet des excitations électriques appliquees au tissu musculaire du coeur. Compt. Rend. d l'Acad. des Science. £9, 203. Meyerhof, O. 1924. Chemical dynamics of life phenomena. (Philadelphia, Lippincott) Meyerhof, Oey Lohmann Es, and Meier, iH. 1925. fiver die synthese des Kohlenhydrates fm Muskel. Biochem. Zeit. 157, 459. Mines , G. He. : 1913. On the summation of contractions. Journ. Physiol. 16, 1. Redfield; A. C. and Medearis, D. N. 1926. The content of lactic acid and the development of tension in cardiac muscle, Am. J. Physiol. ais 662. Robertson, 1. Be. 1908. On the biochemical relationship between the "Staire case” phenomenon and fatigue. Biochem. Zeits. Festbandt fur H. J. Hamburger, 187. Smith, H. 7. ~~ 1926. The action of acids on turtle heart muscle with reference to the penetration of anions. Am. J. Physiol. 26, 411. Trendelenburg, ¥. 1903. @ntersuchungen uber das Verhalten des Herzmuskels bei rythmischer electrisbher Reizung. Archiv. fiir Anat. u. Physiol. Physiol. 1903, 271. Trendelenburg,; We. 1911. Uber den zeitlichen Ablauf der fefraktarphase am Hefzen. Pflligers Arch. 141 s S718. wast®, H. mu 1922. Die ubernormale phase der erhohung des Herzmgrskels nach einer systole. Feifonr. f. Biel. 15, 289. 1 lly BE K TL i II 0 | 20 £ - A O = Contraction | s L A= Contraction 2 > 25 C 3 O = Contraction 3 c | Basic interval = 9.0 secs. o f= 0 I A c 2 u Boi | | | 20 i FIGURE 3 1 1 1 a A 1 1 X 1 1 1 1 1 1 1 1 1 1 1 | 2 > 4 5 6 7 8 9 10 1 Intervals between | ond 2 in seconds FIGURE 2 < 3 0 | 0 3 ° Oo 2 fo 33 -5 a a i eee 5 i aniip os s [> 2. ran] » > 1% a se wl pies 0 2p > » . Time — = a-'Basid interval’ 2’s 3": $s Peon a erye ao 3B, 922 2s s000 0 90’ 9 % 0 0 a0’ Figure 3 Point A is determined from the average of a large number of measurenentss Figure 4. Upper line~--signal, marking time of stimulus. liddle line---myograph of isometric contraction of ventricle strip. Drum moving rapidly during contractions 1 and 2. Remainder of contractions with drum stationarys Lower linew--time signal, a to b, fifths of seconds. Bas sic irtervel B46 sec., interval between 1 and 2, 2.9 secss Note increased magnitude of contraction 3. 25 in grams Is Tension - O = Contraction | A =Contraction 2 0 = Contraction 3 Basic Interval =6.6:5¢c4. Scheme of Intervals FIGURE 5 wave Intervals between | and 2 in seconds 30 S Nn | I In gram Tension O = Contraction |, Basic interval 6.6 secs A = Contraction O Contraction 3, Interval between land 2=1.6secs FIGURE 6 Pinigns Lp 1 1 1 1 1 1 & i | 1 1 1 1 l y s + ; 1 10 5 4 . Interval after contraction in seconds a a a a a A Figure 7s Basic interval, 8.5 secse A to B, extra stimuli inter posed at 149 secse after basic contractions Note increased amplitude of basic contractions following A and decrease following Be Drum rotating at rapid speed during two sets of contractions. Lower line, a to b, flifths of seconds; roamginder, secs. Sy are RG Ea FO ERR Sg Figure 8. Alteration in amplitude of contraction following period of reste (see texts) Treppe and "inverted" treppe. Figure 9. 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