doctor dray beats headphones NORMAL HEART MUSCLE
Gross anatomy: The mammalian heart is a double pump in which the right side operates as a low pressure system delivering de oxygenated blood to the lungs, while the left side is a high pressure system delivering oxygenated blood to the rest of the body. The walls of the right ventricle are much thinner than those of the left, because the work load is lower for the right side of the heart.
There is a dense cartilaginous ring between the atria and the ventricles, which forms a secure connection for the aorta and the pulmonary artery, and provides mechanical support for the four cardiac valves. The compact semilunar valves in the two outflow tracts operate without external help, but the mitral and tricuspid valves between the atria and the ventricles require the assistance of the papillary muscles and chordae tendineae to prevent them everting into the atria at the peak of the ventricular contraction (systole). This band of connective tissue also isolates the atria electrically from the ventricles, so that the atrioventricular node is the only signalling route between the four chambers.
The ventricular muscle is relatively stiff, and would take some time to fill spontaneously with venous blood during diastole. The thin, flexible atria serve to buffer the incoming venous supply, and their initial contraction at the begining of each cardiac cycle fills the ventricles efficiently in a short space of time.
Ultrastructure: In contrast to the huge polynucleate cells found in voluntary skeletal muscles, cardiac muscle cells are small with only one or two nuclei. The regular arrangement of sarcomeres within the myofibrils gives the tissue a striated pattern (like voluntary muscle) but the cardiac cells are not separately innervated. They lack motor end plates and rely instead on communicating gap junctions to transmit electrical signals directly from one cell to the next. This means that in a normal healthy heart, every cell depolarises every beat. This precludes the progressive fibre recruitment and twitch summation mechanisms that regulate contractile force in skeletal muscles, and requires a completely different system for internal signalling and biochemical control.
Cardiomyocytes are often “X” or “Y” shaped and make end to end contact with several neighbours. This may help to spread the load more evenly. Mechanical tension is transmitted from cell to cell by intercalated disks, which are specialised load bearing structures in the plasmalemma. These always interrupt the regular sequence of tension generating sarcomeres at one of the Z lines. The cytoskeletal protein dystrophin is involved in a separate load bearing system along the length of the cells, and a severe inherited cardiomyopathy eventually develops in patients where the dystrophin gene (or its cardiac promoter) is missing or damaged.
Metabolism: Cardiac muscle can achieve the highest sustained metabolic rate of all the tissues in the human body. Up to 40% of the cell volume may be occupied by mitochondria, and most of the remainder is taken up by contractile fibrils. Adult cardiomyocytes are incapable of cell division and are totally specialised for energy production and mechanical work. The biochemistry of muscle contraction is described in the separate muscle pages.
The continuous energy demand can only be satisfied by aerobic metabolism. The heart’s capacity to generate ATP by anaerobic glycolysis is severely limited, and it will not support normal contractile or electrical activity. Glucose entry into cardiac cells is insulin dependent, and under normal circumstances the organ shows a distinct preference for free fatty acids, ketone bodies and (to a lesser extent) blood lactate, all of which are completely oxidised to carbon dioxide and water.
The heart muscle is supplied with blood via the coronary arteries, which arise from the aorta immediately behind the aortic valves. Most of the cardiac veins drain into the coronary sinus, which empties directly into the right atrium. Cardiac muscle has a very high arteriovenous oxygen extraction, which may exceed 90%. Most tissues extract only about 30% of the available oxygen from the blood. The lack of reserve capacity, and the near absence of any any colateral circulation from vessels supplying other areas of the heart, can lead to catastrophic problems if a major branch of a coronary artery becomes blocked through atherosclerosis, leading to a heart attack. Myocytes downstream of the block die and release their contents into the cardiac veins and lymph ducts. This leads to a charteristic elevation of cardiac enzymes in blood plasma. The dead tissue is known as a myocardial infarct. If the patient survives the affected area is invaded by macrophages and fibroblasts. It is eventually re organised as scar tissue, with a permanent loss of cardiac capacity.
Laplace’s law: is an important physical constraint on cardiac performance. It relates the internal pressure “P” inside a spherical bubble of radius “R” to the surface tension “T” in the walls. The law states that
Bubbles will swell or shrink until this relationship is precisely satisfied. It is very easily derived. But
The law follows directly from the two equations above. The practical effect is that it requires more wall tension to generate the same internal pressure in a large sphere than it does in a small one. Laplace’s law governs fluid pumping by any approximately spherical chamber, including hearts. [It would not, for example, apply to a linear piston pump.] It implies that as the heart fills up with blood then the muscle will find itself at an increasing mechanical disadvantage and the chambers will become more difficult to empty. This has obvious implications for dilated cardiomyopathy, but without some very effective countervailing mechanism, even healthy hearts could not operate successfully.
The Starling mechanism: If the heart chambers are initially distended with blood, the ensuing beat is much more forceful than if the chambers were initially empty. This more than compensates for the mechanical disadvantage imposed by Laplace’s law, so that the aortic output pressure actually rises as the venous filling pressure is increased. It is essential that heart muscle should respond to stretching in this way, since otherwise the circulatory system would be unstable and pumping would become impossible whenever the ventricles were full. The relationship was first reported by Starling about 80 years ago, although the precise mechanism has been disputed. The most likely explanation is that calcium ion release from the sarcoplasmic reticulum is greatly increased when the SR is mechanically stretched. The relationship is not fixed and the shape of the curve depends on the outflow resistance. The graph will be shifted to the left by inotropic agents such as catecholamines which increase the inherent contractility of the heart. Negative inotropes like acetyl choline will move the curve to the right.
The curve “turns over” at very high filling pressures, but this descending limb of the Starling curve is not attained under physiological conditions.
Congestive heart failure is characterised by inadequate contractility, so that the ventricles have difficulty in expelling sufficient blood. This leads to a rise in venous blood pressures, which may, temporarily, achieve a new equilibrium where cardiac output is maintained through the Starling mechanism. However, the raised venous pressures impair fluid drainage from the tissues and produce a variety of serious clinical effects.
Right sided heart failure causes lower limb oedema. Blood pooling in the lower extremities is associated with intravascular clotting and thromboembolism. Left sided heart failure produces pulmonary oedema and respiratory distress. Very frequently both sides of the heart may fail at the same time. digitalis, catecholamines) would be sufficient to resolve the problem. In some circumstances such treatment might be appropriate, but it is likely to increase the cardiac oxygen demand. This may not be helpful in patients suffering from ischaemic heart disease. However, it makes very little difference to the oxygen requirement whether or not the heart actually succeeds in emptying. The principal determinant for cardiac oxygen consumption is the PT integral (the area under the left ventricular pressure versus time curve) and the volume of blood pumped has only a minor influence on the result. It may therefore be more effective to treat congestive heart failure with diuretics (which relieve venous congestion by reducing the total blood volume) and by lowering the peripheral vascular resistance. These measures will assist ventricular emptying by reducing the work load on the heart.
Electrical activity: Unlike voluntary skeletal muscles, cardiac muscle does not require any nervous stimulation in order to contract. Each beat is initiated by the spontaneous depolarisation of pacemaker cells in the sino atrial (SA) node, located where the great veins empty into the right atrium. These cells trigger the neighbouring atrial cells by direct electrical contacts and a wave of depolarisation spreads out over the atria, eventually exciting the atrio ventricular (AV) node, located at the top of the interventricular septum. Contraction of the atria precedes that of the ventricles, forcing extra blood into the ventricles and eliciting the Starling response. The electrical signal from the AV node is carried to the ventricles by a specialised bundle of conducting tissue (the bundle of His) which divides into several bundle branches within the interventricular septum. [Damage to these conducting bundles, or to the AV node, produces the clinical conditions of partial or complete heart block, where the atria and the ventricles contract independently.] The conducting tissues are derived from modified cardiac muscle cells, and are known as . They have a reduced content of contractile proteins, and a much higher conduction velocity, than ordinary cardiomyocytes. The conducting bundles divide repeatedly as they spread out through the myocardium to coordinate electrical and contractile activity across the heart. Acetyl choline, acting through M2 muscarinic receptors, reduces the spontaneous firing rate of the sinoatrial node, and also depresses conduction velocity through the and the force of the ensuing ventricular contractions. Catecholamines, acting through beta 1 receptors and adenyl cyclase have the opposite effects.
The cardiac cycle: The diagram below shows the principal events in the normal cardiac cycle, for an individual with a blood pressure of 120/80 and a heart rate of 75 beats/min. The papillary muscles are activated early during systole, and prevent the eversion of the delicate leaflets of the mitral and tricuspid valves. [Infarcts that involve these muscles can lead to valvular incompetence.] The first heart sound “lub” is associated with the closure of the mitral and tricuspid valves near point 1 and the second sound “dup” with the closure of the aortic valve at point 2. Three important indices of cardiac contractility are the left ventricular end diastolic pressure [edp] (measured just before the mitral valve closes), the maximum rate of left ventricular pressure increase [dP/dT (max)] and the peak systolic pressure [psp]. Ventricular activation is actually spread over about 75 msec, and the action potential therefore represents a “typical” cell. Note the very different voltage scales used for the ECG and the action potential recording.
The electrocardiogram [ECG] is an important non invasive source of diagnostic information. Although a constant cardiac membrane potential produces no measurable electrical effect at the surface of the body, the spread of excitation through the heart generates small resultant voltages which can be detected by electrodes attached to the skin. The spread of excitation is affected by many disease processes, and therefore provides important clues about the nature of the underlying defects. The ECG signal is about one hundred times smaller than the action potentials recorded using microelectrodes from individual cells. It reflects the summation of innumerable tiny currents from billions of cardiac cells, and is broadly proportional to muscle mass: the left ventricular signals, for example, are much bigger than the atrial effects. The amplitude of the signal is reduced in dilated cardiomyopathy, although the reasons for this are not entirely clear.
The initial P wave is produced by the atrial depolarisation. This is followed by the QRS complex as electrical excitation spreads through the ventricles, and finally by the T wave as the ventricles repolarise towards the end of each beat. By convention the main upstroke on each trace is always called the “R” wave. It does not always reflect exactly the same event the precise shape of the ECG varies with the position of the recording electrodes, and there are considerable anatomical variations from one subject to the next.
The heart is a complex three dimensional structure, but it is convenient to represent the source of the ECG waveforms by a simple electrical dipole that changes both its size and orientation as the wave of depolarisation spreads through the muscle. It is important to realise that we are observing a vector quantity one that has both magnitude and direction, although we can only record its scalar projections on the surface of the skin. The usual locations of the recording electrodes for a full diagnostic ECG are marked on the diagram below, but for routine patient monitoring only two electrodes are normally employed.
For reasons of practical convenience the electrodes for right arm (RA) and left arm (LA) are normally attached at the wrists, and the “midline” (LL) electrode is actually attached to the left ankle. This has only minor effects on the results. Three channels [often called “leads”] are usually recorded simultaneously, and the equipment can be used in three distinct ways:
To compare the signals from the RA, LA and LL electrodes, using the polarities show on the diagram above. The positive and negative inputs to lead I [also called channel I] are connected to LA and RA respectively, lead II between LL and RA and lead III between LL and LA. These three leads are often referred to as the limb leads to distinguish them from the precordial leads attached to the front of the chest. The objective is to determine the spatial orientation of the main electrical vector generating the QRS complex at the beginning of systole. This vector normally points downwards to the left at about 60 degrees below the horizontal, but in healthy people may be anywhere between horizontally left and vertically downwards. Deviations beyond this range are described as right or left axis deviation, and may indicate a variety of pathological states, including heart blocks, abnormal conduction pathways, premature ventricular complexes (PVCs), left or right sided hypertrophy, lung diseases and tumours.
To compare the signal from one limb electrode with the average signal from the other two. Thus the aVR lead compares the signal from the right arm electrode with the left arm and left leg connected together, aVL analogously with the left arm, and aVF with the left foot. This yields similar information to leads I, II and III but the coordinate system is effectively rotated through 30 degrees, and the signals are generally larger, which may be more convenient.