CV Physiology | Cardiac Muscle Force-Velocity Relationship
force-velocity relations studied in this fashion, however . level of afterload, two consecutive cardiac cycles representation of muscle contraction,11 shorten-. The classical study describing the force-velocity relationship for cardiac muscle was The heavier the object that we lift, the slower our muscles contract. This fundamental property of muscle indicates that mechanical power Force- sarcomere velocity relationships (left panel) and collectively move the actin filament during contraction.
The x-intercept in the force-velocity relationship represents the point at which the afterload is so great that the muscle fiber cannot shorten, and therefore represents the maximal isometric force. The y-intercept represents an extrapolated value for the maximal velocity of shortening Vmax that would be achieved if there were no afterload. The value was extrapolated by Sonnenblick because it cannot be measured experimentally because the papillary muscle preparation cannot contract without a finite preload, which becomes the afterload during shortening in the absence of an additional afterload.
It is important to note that a cardiac muscle fiber does not operate on a single force-velocity curve. This relationship is altered by changes in both preload and inotropy. The former shares some similarities with skeletal muscle; the latter, however, is unique to cardiac muscle. How Preload Affects the Force-Velocity Relationship If preload is increased, cardiac muscle fibers will have a greater velocity of shortening at a given afterload see figure.
Conversely, if preload decreases, the velocity of shortening decreases at a given afterload. This occurs because the length-tension relationship dictates that as the preload is increased, there is an increase in active tension development.
Once the fiber begins to shorten, the increased tension generating capability at the increased preload results in a greater velocity of shortening. In other words, increasing the preload enables to muscle to contract faster against a given afterload. Uncertainty about internal energy-losses in the muscle and the ordering and synchronicity of activation adds further difficulty here.
At the moment, therefore, although detail of the ultrastructure of the contractile apparatus is becoming available, our understanding of myocardial mechanics remains incomplete.
Chapter 11 part a
The behaviour of the muscle is still described in terms of crude functional models, and the behaviour of the contracting heart-chamber can only be described qualitatively because of the geometrical uncertainties, even though the time-course and magnitude of the fluid-dynamic events in the cardiac cycle are being measured with increasing precision in both animals and man. Anatomy of the heart Each of the cardiac pumps consists of a low-pressure chamber atriumwhich is filled from a vein system and empties via a non-return valve into a high-pressure chamber ventricle.
The ventricle in turn passes blood on through a second non-return valve to an arterial system Fig. Diagrammatic representation of anatomy and directions of blood flow in the heart.
The veins draining into them communicate with them without valves. The right heart receives blood from the body tissues via the systemic veins and pumps it into the pulmonary lung arteries. The left heart receives this blood from the pulmonary veins and pumps it into the systemic main body arterial circulation, via the aorta and its branches. The two atria are comparable in structure; their walls are thin and relatively compliant, and they are separated from each other by a common wall, the atrial septum.
The valves separating the atria from the ventricles atrioventricular valves differ slightly in structure on the two sides of the heart, the one on the right tricuspid having three cusps, the one on the left mitral two. These cusps consist of flaps, attached along one edge to a fibrous ring within the wall of the heart, and with free edges projecting into the heart-cavity.
They are extremely thin about 0. Each chorda connects to the free edges of two cusps where they come in contact with each other when the valve closes; thus tension in the chorda generated by contraction of the papillary muscle at the beginning of systole counteracts the tendency of the increase in intraventricular pressure to turn the valve inside out and allow leakback into the atrium.
There appears to be a self-contained mechanism for closure of these valves see p. The exit valves from the ventricles pulmonary and aortic are very similar to each other, each consisting of three cusps with free margins reaching to the wall of the valve-ring. This arrangement allows opening to the full cross-sectional area of the valve-ring without distortion of the cusps.
These cusps are not tethered, but can nonetheless support considerable pressure differences in the case of the aortic valve, approximately 1. They are also extremely efficient, since only trivial backflow occurs through them during closure which occurs more than 30 million times a year.
Not surprisingly, their behaviour has been a source of interest for many years; in the fifteenth century Leonardo da Vinci examined their structure and made speculative drawings of flow patterns through them which have since proved remarkably realistic; their mechanism of action has recently been studied in detail see p.
The four valve orifices in the heart are aligned approximately in a single plane, and the cusps of each are attached at their bases to a stiff ring of fibrous tissue Fig. Relationships of various structures in the heart. The 'skeleton' of the heart, consisting mainly of the fibrous valve-rings, also supports both atria and ventricles, and the two great arteries.
The four rings are in turn connected to each other by fibrous tissue so that the valve apparatuses are set in a stiff framework to which the muscle-fibres of each chamber are attached—the atria on one side, the ventricles on the other; and the pulmonary artery and aorta also attach at their origins to this plane of fibrous tissue. The whole heart is contained in a thin fibrous tissue bag, the pericardium, which in turn is attached to other structures within the chest, and through these to the vertebral column.
The stress-strain relationship of the pericardium is, as can be inferred from Fig. Pressure-volume curve of pericardium of dog. By permission of the American Heart Association, Inc. At normal diastolic heart volumes, the pericardium is only slightly stretched, and probably does not appreciably affect cardiac filling; in certain diseases where fluid accumulates within the pericardium, its constraint can restrict diastolic filling of the ventricles and severely reduce cardiac output see p.
The left ventricle is the only chamber whose wall-structure has been examined systematically. Recent studies of microscopic sections taken serially through the whole thickness of the wall have shown that older concepts of a ventricular wall made up of clearly defined muscle layers are incorrect, and that there is a well-ordered continuous distribution of fibre-orientation Fig. Muscle fibre orientation in wall of left ventricle, a The orientation of the long axis of the fibres at successive depths from the outer surface, b The way in which the angle made by the fibre with the circumferential plane of the LV changes continuously through the wall after Streeter et al.
The innermost endocardial fibres run predominantly longitudinally from the fibrous region around the valves the base to the other end of the roughly elliptical chamber the apex ; the fibres slightly further out into the wall lie at a slight angle to the axis of the chamber, so that the fibres spiral slightly as they run towards the apex. This angulation increases in successively deeper fibres so that those approximately half-way through the wall run parallel to the shorter axis of the chamber, i.
This arrangement gives the ventricle great strength even though individual muscle fibres can only bear tension axially, since a stress applied to the wall in outer wall any direction can be resisted by at least a proportion of the muscle fibres, and there is no direction or plane of weakness.
Note that fibres do not have to terminate at the apex; they can turn and spiral back towards the base like string wound spirally on a stick. As can be inferred from Fig. The Cardiac Cycle Electrical events. 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.
- Cardiac Muscle Force-Velocity Relationship
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.
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.