Sarcomere length tension relationship cardiac muscle tissue

The cellular basis of the length-tension relation in cardiac muscle.

sarcomere length tension relationship cardiac muscle tissue

The relation between muscle length or sarcomere length and developed tension for lengths . of the sarcomere length-tension relation of skinned cardiac cells. Los Angeles. SYNOPSIS. The distinguishing mechanical characteristics of cardiac muscle are basis of the regulatory function of the force-velocity relation. process of cardiac hypertrophy (the growth of heart muscle cells rather than the Because of the structural considerations [29], sarcomere lengths longer than or The length-tension relationship of cardiac muscle does not account well for.

The contraction cycle of the heart is initiated in a localized area of nervous tissue in the wall of the right atrium known as the pacemaker or sino-atrial node. This has the inherent property of cyclical depolarization and repolarization the latter process being dependent upon metabolic energy, derived ultimately from metabolism within the cells. When depolarization occurs in the pacemaker, it spreads at about 1 m s-1 into and through the surrounding muscle of the right and left atrial walls causing atrial contraction and then into a discrete nervous pathway the atrio-ventricular bundle, or bundle of His which passes through the fibrous tissue around the tricuspid valve ring into the muscular septum between the two ventricles; here it divides, and spreads into the muscle mass of each ventricle, terminating in a series of fine fibres amongst the muscle-cells Purkinje fibres.

The wave of depolarization spreads through this system rapidly 5 m s-1and therefore depolarization and contraction of all the muscle-fibres in both right and left ventricles are relatively synchronous; the ventricular depolarization potential on the electrocardiogram—the 'QRS' component—lasts less than 0. A number of nervous and hormonal influences which originate outside the heart may act on the pacemaker to cause alterations of frequency, and may modify the conduction velocity of the depolarization wave through the heart; but the orderly sequence of atrial and ventricular contraction which follows pacemaker depolarization is ensured largely by the layout of the conducting pathways.

The cycles of depolarization and repolarization which occur in cardiac muscle generate small electrical potentials, and with suitably located electrodes these Can be picked up at the surface of the body, and amplified and recorded as the electrocardiogram.

A typical tracing is shown at the top of Fig. Semi-diagrammatic illustration of the events on the left side of the heart during the cardiac cycle. All pressures related to atmospheric. The origin of the 'a' and 'v' wave in atrial pressure is discussed in the text, p.

Depolarization of the atria produces a small deflection known as the T' wave; this is followed after a delay of about 0. This reflects depolarization of the two ventricles, and is followed by a final component, the T' wave, which is generated during repolarization of the ventricles. The time relationships between these summed electrical potentials and the mechanical events on the left side of the heart can be deduced from Fig.

As has just been mentioned, the onset of ventricular contraction ventricular muscle depolarization is signalled electrically by the QRS complex of the electrocardiogram. Both ventricles contract almost synchronously see Fig.

Semi-diagrammatic illustration of pressure and flow occurring simultaneously on the left and right sides of the heart during the cardiac cycle. The sequence of events is illustrated in Fig. Depolarization is followed after a very short interval by the onset of active tension development see p. At this stage, the aortic valve is still held closed because the pressure in the aorta exceeds that in the left ventricle, and the cusps of the mitral valve are moving together as flow into the ventricle dwindles.

Almost immediately, ventricular pressure rises above atrial pressure, and a brief period of backward flow from ventricle to atrium occurs, terminated by closure of the mitral valve. This is accompanied by a sound, audible at the chest wall and known clinically as the first heart sound. This marks the onset of systole, the period of ventricular contraction. The second heart sound marks the start of diastole, the period of ventricular dilatation.

Note that these periods are defined in relation to the heart sounds and not in terms of muscle mechanics or the electrocardiogram. In the ventricle, wall-tension now starts to rise extremely rapidly until the pressure within the cavity exceeds that in the aorta.

There is no change in ventricular volume during this period, since blood is effectively incompressible; it is therefore known as the isovolumetric period. In the older literature, it is often referred to as the isometric period; however, it is now clear that the ventricle does change shape during this phase, even though volume is constant, and the term isovolumic, or isovolumetric, is therefore preferable.

When the pressure within the ventricle exceeds aortic pressure, there is a net force operating to open the aortic valve, and the ejection phase of systole commences. The blood in the ventricle and proximal aorta undergoes rapid forward acceleration as left ventricular volume diminishes. Ventricular wall-tension then falls, the pressure difference between ventricle and aorta is reversed, and deceleration of aortic flow occurs. Finally, there is a brief period of backflow before aortic valve closure takes place, accompanied by the second heart sound.

There then follows another isovolumetric period during which the muscle relaxes and ventricular pressure falls. At the same time, pressure in the left atrium is rising as it fills with blood from the pulmonary veins the V wave. When its pressure exceeds that in the left ventricle, the mitral valve reopens.

Ventricular filling then occurs, under the influence of a pressure difference generated at first passively and then by active shortening of the muscle fibres of the atrial wall; this active atrial contraction atrial systole is heralded electrically by the 'P' wave of the electrocardiogram, and marked mechanically by a brief increase in atrial pressure the 'a' wave.

Very shortly after this, activation of the ventricular muscle occurs and the cycle recommences. In normal man, the heart-rate may range from about 45 min-1 resting athlete up to slightly above min-1 on maximal exercise.

Systole is much shorter than diastole at the lower heart-rates, occupying about a third of the cycle Fig. The volume ejected from the ventricle with each beat stroke volume is normally in the range cm3 at rest; a smaller volume remains in the ventricle - i.

The variation in stroke volume with exercise is much less than that in the heart-rate; thus increases in cardiac output in severe exercise five-fold or more depend much more on rate increase than on stroke volume increase. Blood pressure rises in both the pulmonary artery and the aorta on exercise, but much more modestly than does the flow, because recruitment of additional vessels in the microcirculation, or dilatation of previously constricted ones, lowers the downstream resistance to flow.

Properties of cardiac muscle Structure. Under the light microscope, the myocardium is seen to be made up of elongated muscle cells running in columns and having centrally placed nuclei and abundant mitochondria Fig. Electron micrograph of parts of three cardiac muscle fibres and an adjacent capillary Cap in longitudinal section.

The two upper cells are joined end to end by a typical steplike intercalated disc In D. Rows of mitochondria Mt appear to divide the contractile substance into myofibril-like units but, unlike the true myofibrils of skeletal muscle, these branch and rejoin and are quite variable in width.

Lipid droplets Lp somewhat distorted in specimen preparation are found between the ends of the mitochondria. The structure of a single sarcomere is shown at higher magnification in Fig. From Fawcett and McNutt As in skeletal muscle, the fibres have a cross-striated appearance which is due to the structure of the contractile units, or myoftbrils, lying within the cells.

However, the motor nerve filaments, neuromuscular junctions, and the length-monitoring muscle-spindles present in skeletal muscle are absent from cardiac muscle; and further points of difference are that the muscle-cells branch repeatedly, and have abundant collagen fibres between them.

The limit of definition of the light microscope is about 0. Since there did not appear to be cell-membranes running across the fibres, it was assumed for some time that they had a syncytial structure, i. However, electron microscopy has revealed that the cell-membrane has two layers, with the inner layer passing across the fibres and dividing them every mm into structurally separate cells, about mm in diameter.

At intervals of about 2 mm all along each such cell there are extremely fine invaginations of the cell-membrane known as T-tubules, which have been shown to provide for almost simultaneous activation of all the myofibrils in the cell when the membrane is depolarized.

Numerous other fine details of cell structure have been described, and a great deal of recent progress has been made in clarifying the biochemical reactions which release energy for contraction and repolarization.

However, we will concentrate only on the contractile apparatus, since our interest lies in the mechanics of the muscle-fibres. As mentioned previously, the contractile elements of each cell are the myofibrils, which run parallel to the long axis and show a repeating pattern of cross-striation. The myofibrils themselves actually consist of bundles of myofilaments, and the cross-striations repeat themselves because the myofilaments are made up of repeating chains of sarcomeres. The sarcomere is the fundamental contractile apparatus; its structure was first described in skeletal muscle, and has been confirmed in cardiac muscle with only minor differences.

Each sarcomere is limited by two adjacent narrow bands known as Z bands or lines Fig. When the muscle-fibre is stretched, the distance between the Z bands widens; but the A bands remain the same length.

All this can be distinguished under the light microscope; sarcomere-length increases with increase of overall muscle-length, and in heart muscle at its diastolic length is about 2.

A series of elegant electron microscopy studies has shown these bands to be due to partially overlapping parallel arrays of filaments, arranged as in Fig. The sarcomere is bounded by a pair of Z bands. Within it is the dark central A band marked at its midpoint by the darker m line and two paler I bands. Note that at this length the actin filaments do not reach past the midline of the sarcomere, so that no 'contraction band' is visible. See text for details. From Sonnenblick, Spiro, and Spotnitz The thicker filaments making up the A bands are composed primarily of the protein myosin; the thinner rods which interdigitate with them are actin.

When the muscle is stretched, the Z bands move apart and the actin rods slide along and partially disengage from the myosin rods; thus the I bands widen. When the muscle contracts, the reverse happens, until at very short muscle-lengths the I bands disappear, and new dark bands 'contraction bands' appear where the actin rod tips overlap each other at the centre of the A band. This occurs at sarcomere lengths less than 1.

In skeletal muscle, there are fine cross-bridges between the actin and myosin filaments, projecting from each thick myosin filament. Each myosin filament is surrounded by six actin filaments, and therefore makes one cross-bridge with each of these in a length of approximately 40 nm. The cross-bridges seem likely to have an important role in the shortening process of striated muscle, since the filaments themselves are probably too far apart for direct interaction; one suggestion is that during contraction the cross-bridges may move back and forth, hooking up to specific sites on the actin filaments and drawing them on before releasing the linkage and moving back to a new linkage site.

Thus during activity they would have a ratchet action; with the cessation of activity the filaments would be free to slide apart passively. To date, this remains a speculative explanation, particularly when applied to cardiac muscle.

Static mechanical properties of cardiac muscle. The 'sliding filament' description of sarcomere behaviour outlined above is doubly compelling because it not only fits with the visible ultra-structure of muscle, but offers an explanation of one of its fundamental mechanical properties - the length-tension relationship. When a muscle is held at a constant length and stimulated electrically it generates tension active or developed tension over and above any resting tension present prior to stimulation.

If this experiment is repeated with successive small increments in length, the active tension is found to increase successively to a peak and then decline Fig. Typical length-tension curves for skeletal and cardiac muscle. In each case resting and active tension was plotted against length as the muscle was held at a series of lengths and stimulated electrically to contract.

The ordinates show tension, expressed in kilograms per square centimetre of muscle cross-sectional area. Note the difference in scaling of the two graphs. The abscissae show sarcomere lengths, relative to the lengths Lmax, at which the maximum active tension was developed; in these experiments Lmax was 2.

After Spiro and Sonnenblick This is true for a wide variety of muscle, and in skeletal muscle and probably also cardiac muscle the peak of the length-tension relation comes when the degree of stretch brings sarcomere length to about 2.

Sarcomere length-tension relationship

This may be more apparent than real, since heart muscle contains a greater bulk of non-contractile tissue such as collagen and mitochondria, and the muscle fibres are not all parallel. In muscle which has contracted at sarcomere lengths of less than 2. This overlap lessens as the muscle is stretched, until at a sarcomere length of 2.

It is at this length that the maximum active tension can be developed. As the sarcomere is stretched beyond this, the actin rods are progressively withdrawn from between the myosin rods, and fewer cross-linkages can form. In this length range, the active tension developed in a contraction declines linearly with length increase, until at a sarcomere length of about 3.

In skeletal muscle this relationship between sarcomere length and tension has been firmly established, and its functional significance is generally agreed. The behaviour of sarcomeres in cardiac muscle has been investigated much less thoroughly; under physiological conditions they appear to operate in the length range from about l. However, relatively few observations have been made on the relationship between sarcomere length and developed tension in cardiac muscle, and these are to some extent conflicting.

This may be because of technical problems, particularly those of tissue distortion during histo logical preparation; methods have recently been developed to measure sarcomere length in vivo, and these may resolve the question. At present, it seems well established that no active tension is developed at sarcomere lengths less than about 1. In between it is not clear whether increasing tension is the result of successive increments in sarcomere length as in skeletal muscle, or recruitment of increasing numbers of sarcomeres in muscle-fibres which were buckled at short muscle-lengths and are straightened and then stretched as the muscle lengthens.

Furthermore, there is recent evidence that the curve relating tension and sarcomere length Fig. We need a more detailed knowledge of the behaviour of actin-myosin cross-linkages to settle these uncertainties.

In skeletal muscle, the linear relationship between muscle-length and sarcomere length is maintained until the latter reaches at least 3. For heart muscle, the situation at high degrees of stretch is different. Sarcomeres will lengthen to only about 2. This situation does not arise in the normal heart and seems very unlikely even in the failing or pathological heart; in acute experiments where the relaxed left ventricle was distended with pressures as high as mm Hg far in excess of the levels reached even in severe heart disease the sarcomeres in the ventricular wall had an average length of only 2.

Dynamic mechanical properties of cardiac muscle. The length-tension curve describes an important property of muscle under static conditions - held at a constant length both before and during activity - but it throws no light on the dynamics of muscular contraction, which are of fundamental importance to any understanding of heart muscle performance.

A stimulated muscle goes through a period of mechanical activity the 'active state' which reflects the release of energy derived from chemical reactions and has measurable properties both of duration and intensity. Enormous progress has been made in elucidating and measuring both the biochemical steps which yield energy, and the mechanical behaviour which is the expression of this energy release.

The literature is voluminous, reflecting both the technical difficulties involved in research on the myocardium and its innate complexity, and the subject can only be briefly surveyed here. The commonest material used for experimental study of the mechanical properties of heart muscle has been papillary muscle, removed from the right ventricles of young animals under anaesthesia.

It can be obtained in this way as extremely thin strips a few millimetres in length, and made up of numbers of fairly parallel muscle fibres. When such papillary muscles are mounted in oxygenated, nutrient media of appropriate ionic and osmotic properties, they preserve their contractile properties in response to electrical stimulation for long periods.

These contractile properties have been interpreted largely in terms of very simple mechanical models; to demonstrate why such models were chosen it is necessary briefly to describe some early experimental work carried out on skeletal muscle.

sarcomere length tension relationship cardiac muscle tissue

Intact skeletal muscles can be removed easily from small animals such as the frog, and a number of workers in the early years of the twentieth century studied these muscles, stimulating them electrically and examining the mechanical properties and heat production during contraction the latter phenomenon having been demonstrated by Helmholtz over fifty years previously.

As was mentioned earlier, electrical stimulation of muscle leads to tension development. In the resting state, a potential difference of about 90 mV is maintained across the membrane of the muscle-cell - the resting potential.

An externally applied shock can cause transient reversal of polarity of this potential, followed by slow recovery. This discharge, which is known as the action potential, triggers the release of calcium ions from stores within the muscle-cell, and these somehow activate the cross-linkages between the actin and myosin rods in the contractile apparatus of the sarcomeres. This whole process occurs within milliseconds, and the muscle cell is then capable of contracting i.

Thus a single electrical stimulus applied to a muscle-fibre causes a short-lived contraction appropriately known as a twitch. A chain of stimuli causes repetitive twitches, and in skeletal muscle if the stimulation frequency is high enough the twitches will fuse together to give a sustained contraction. This is known as a tetanus, and the corresponding train of shocks is a tetanic stimulus.

For a given muscle preparation, the tension generated in each twitch or tetanus will increase with increasing stimulus strength until a maximum is reached which is highly reproducible over long periods of time. If the muscle is held at constant length, the twitch or tetanus is known as isometric; if it is allowed to shorten, the force if any opposing shortening is described as the load or afterload and if this force is constant, which implies that all accelerations of the load are very small compared to that due to gravity, the contraction is called isotonic.

Since maximal isometric contractions were found to be highly reproducible, they were used experimentally as the baseline condition; in this case the muscle generated heat during the course of a stimulation cycle, but since no shortening occurred, no external work was done work, or energy, is equivalent to force times distance.

When muscles were allowed to shorten by a distance x against a load or force P, not only were Px units of work done, but an extra amount of heat was released.

This effect of shortening on heat production is known as the 'Fenn effect' after its discoverer; Fenn an American physiologist who did this work in also demonstrated the converse to be true - if a muscle was stretched during stimulation, it gave out less heat than when held at constant length.

Length-tension relationship

In describing this experiment, Fenn coined a phrase, 'negative work', which has given pain to physical scientists ever since; this is unfortunate, since the implication of the experiment - that the mechanical conditions during contraction control the amount of energy released - is fascinating and appears to have been little explored.

The explanation of this liberation of excess heat on shortening came some years later when instruments capable of following heat-production instant by instant through the contraction and relaxation cycle became available.

It was then shown in a famous series of experiments carried out by A. Hill that the extra heat associated with shortening is proportional to the distance x shortened; thus it is equivalent to ax units of work where the constant a has the dimensions of force. This rate of energy liberation was found experimentally to increase as load diminished, having its highest value when the load was zero and being zero when the muscle exerted its maximum force in an isometric contraction.

Thus the properties predicted from thermal measurements were open to confirmation by purely mechanical experiments, and were indeed verified when the velocity with which a muscle could shorten isotonically against various loads was examined Fig. Relationship between load P grams-weight and velocity of shortening v cm s-1 in isotonic shortening of frog skeletal muscle.

The points were obtained experimentally; the line was derived from Equation The thermal observations were, however, of great importance in another way, since they suggested the first conceptual mechanical model of the muscle fibre.

Observations on the course of heat release in the very early stages of stimulation revealed that it was similar for both isometric and isotonic contractions. This suggested that similar mechanical events were occurring in the early stages of both types of contraction, and since the length of the muscle fibre could not change in an isometric contraction, the idea arose of a contractile element in the muscle, which shortened on stimulation but which was linked in series to an elastic element that could lengthen if muscle length was held constant Fig.

Mechanical models of muscle. The force-velocity relationship described above was assumed to describe the properties of the contractile element, since in steady shortening under isotonic conditions the elastic element would have constant length and would not contribute. It should be stressed that Hill was examining the properties of skeletal muscle under very particular conditions.

First, the muscle was stimulated with trains of high frequency shocks tetaniso that a prolonged and maximal response occurred. Thus each observation was carried out with a constant load and a steady velocity of shortening. The real physical properties of the series elastic element were not considered, since it was at constant length throughout.

Similarly, the time-course of development or decay of force was ignored. Furthermore, resting tension was very small at the muscle-lengths used approximately 2 per cent of active tensionand therefore a model with two elements was adequate.

The addition of a component to account for tension in the resting state parallel elastic component, as in Fig. Finally, the exact nature and location of the contractile element and the series elastic element also remained undefined; structures such as tendons might represent a genuine elastic element, or the internal contractile mechanisms might be elastic. Nonetheless, this 'two-element' model of active skeletal muscle achieved widespread acceptance, since it explained a range of mechanical and thermal observations.

It was natural, in view of the structural similarity which exists between sarcomeres in cardiac and skeletal muscle, to consider its applicability also to cardiac muscle.

And so there is a little bit of work to be done. But I still wouldn't say that it's maximal force. Because look, you still have some overlap issues. Remember, these myosins, right here, they're not able to work. And neither are these, because of this blockage that's happening here. Because of the fact that, of course, actin has a certain polarity.

So they're getting blocked. They can't do their work. And so even though you get some force of contraction, it wouldn't be maximal. So I'll put something like this. This will be our second spot. This will be number two. Now in number three, things are going to get much better. So you'll see very quickly now you have a much more spread out situation.

Where now these are actually-- these actins are really not going to be in the way of each other. You can see they're not bumping into each other, they're not in the way of each other at all. And so all of the myosins can get to work.

So the z-discs are now out here. My overall sarcomere, of course, as I said, was from z-disc to z-disc. So my sarcomere is getting longer. And you can also see that because now there's more titin, right? And there isn't actually more titin. I shouldn't use that phrase. But the titin is stretched out. So here, more work is going to get done. And now my force, I would say, is maximal.

So I've got lots, and lots of force finally. And so it would be something like this. And so based on my curve, I've also demonstrated another point, which is that, the first issue, getting us from point one to point two, really helped a lot. I mean, that was the big, big deal. Because you needed some space here. Again, this space really was necessary to do work at all. And now that we've gotten rid of the overlap issue, now that we've gotten these last few myosins working, we have even more gain.

But the gain was really-- the biggest advantage was in that first step. Now as we go on, let's go to step four. So this is step four now. As we go here, you're going to basically see that this is going to continue to work really well. Because you have your actin, like that, and all of your myosins are still involved in making sure that they can squeeze. So all the myosins are working. And our titin is just a little bit more stretched out than it was before.

And our force of contraction is going to be maximal. And you're going to have-- and so here, I'm drawing the z-discs again.

They're very spread out. Our sarcomere is getting longer and longer. And our force of contraction is the same.

Length-tension relationship :: Sliding filament theory

Now let's just take a pause there and say, why is it the same? Why did it not go up? Well, it's because here, in stage three, you had 20 myosin heads working.

Up here, you had something like 16 out of 20 working. Here, we said maybe zero out of 20 right? And here, you again have 20 out of So you still have an advantage in terms of all of the myosins working. But there's no difference between 0.

Because again, all the myosins are working. So now in stage five, we kind of take this a little too far, right?

sarcomere length tension relationship cardiac muscle tissue

So let me actually just make a little bit of space here. We take this a little bit too far in the sense that our actin is going to slip out all the way over here. And it's going to be out all the way over here. So we've got a huge, huge gap now. And, of course, our titin is completely stretched out. It's about as stretched out as our titin is going to get. This green titin protein. And now the question is, of course, would you get any force? And the answer's probably no. Because the myosins aren't even touching the actins anymore.

So really, again, you have zero out of 20 myosins at work. And of course, that means that then the amount of force would be zero. So we go back down to zero. So this is part five. So you can see now, as we've gotten longer and longer, things were good for a while, but then they drifted all the way back down.

And this curve that I'm showing you, this tension-length curve, is now based on exactly what you see on the right. It's based completely on the idea that as you stretch things out, the amount of force changes depending on the length of the sarcomere.