In this article we will discuss about:- 1. Origin and Development of Cardiac Muscle 2. Histology of Cardiac Muscle 3. Fine Structure 4. Blood Vessels, Lymphatics and Nerves 5. Metabolism.
Origin and Development of Cardiac Muscle:
Cardiac muscles in the embryo are originated from the mesenchymal tissue. They are formed of the splanchnopleure adjoining the endothelium of the cardiac primordium. The processes of the star-shaped cells have got desmosome- like attachments to each other which are ultimately developed into the intercalated discs.
The cells (myoblasts) divide mitotically and gradually the fine bundles of myofibrils begin to appear. Electron micrographically, the Z-lines are the first appeared cross-striations. The Purkinje fibres also develop from same primary star-shaped cell reticulum as that of the myocardium.
The cardiac muscle (involuntary striated) contracts rhythmically and automatically, which is particularly maintaining the life process of the living system by assisting the supply of nutrients, O2 and removal of metabolic waste products. Morphologically, it can be distinguished from smooth and skeletal muscles, though it carries some common characters to each other.
The main differences between cardiac and skeletal muscles are:
i. The spontaneous nature of contraction and rhythmicity which is not subject to voluntary control.
ii. The fibres are not simple cylindrical but they bifurcate and come in contact with that of the neighbouring fibres and ultimately form a three dimensional network which causes the false syncytial appearance under light microscope.
iii. The nucleus is single and placed deep in the sarcoplasm more or less at the centre.
The cardiac muscles are actually forming the muscular body of the heart (muscle layer of the heart). These muscles are also present in small amounts in the great vessels ending in or opening from the heart.
Histology of Cardiac Muscle:
The cardiac muscle fibres are separated from each other by the connective tissue endomysium along with blood vessels and lymphatics. The cardiac muscle fibres are not made up of one straight simple cylinder but they have got short cylindrical branches in all directions (in any dimension). These branches are coming in contact with that of the adjacent fibres, ultimately forming a three-dimensional network.
Under light microscope these networks appear as syncytium (cytoplasmic continuation in between neighbouring cells) which was also supported as the property of the cardiac muscle that if it contracts it will contract as a whole. But electron micrograph reveals that these branches are not acting as cytoplasmic bridge but they are separated from each other by special surface specialization, the intercalated disc. These discs appear as dark lines under light microscope and pass in irregular step-like configuration across the fibres at fairly regular intervals and at the level of the I-band.
The sarcolemma of the cardiac muscle is more or less similar to skeletal muscle. The mitochondria are more numerous and the cytoplasm is more abundant. The mitochondria are arranged longitudinally and are present in between the myofibrils in rows. The nucleus is elongated centrally placed in the diverging myofibrils.
A small Golgi apparatus is present at one pole with a few lipid droplets. As age increased the lipofuchsin (lipofuscin) pigments are deposited near the nucleus and may be much extensive to give the brownish appearance of the heart—the brown atrophy of the heart. The sarcoplasm contains more glycogen than that of the skeletal muscle. The patterns of the A-, I-, Z-, H-band, etc., are identical with that of the skeletal muscle.
Fine Structure of Cardiac Muscle:
Under electron microscope, the myofibrils, made up of myofilaments, are more or less similar to that of the skeletal muscle. The myofilaments are not continuous in the adjacent fibres of the longitudinal order, i.e., they are limited to the individual fibres, in other words, similar to the skeletal muscle. Yet groupings of the myofilaments (made up of actin and myosin) are not complete to form the myofibrils as that of the skeletal muscle.
These myofibrils are delineated by the sarcoplasmic reticulum and sarcoplasm. Sarcoplasm contains a large amount of mitochondria (average 2.5 µ in length, but often they appear as 7-8µ in length) along the long axis. Mitochondria often remain completely surrounded by myofilaments. So the myofilaments of the cardiac muscle fibres form a continuum which looks like a large cylindrical mass made up of parallel myofilaments sub-divided by fusiform clefts of the sarcoplasm occupied by mitochondria.
Sarcotubular System:
i. T-System:
This T-system is the tubular invagination of the sarcolemma of the cardiac muscle and is larger in diameter than that of the skeletal muscle. The T-tubules are present at the Z-line in the cardiac muscle fibres, but the same are at the A-I junction in case of the mammalian skeletal muscle.
The functional significance of the locational difference is not yet understood. These tubules also increase the surface for metabolic exchange in between the interior of the cardiac muscle fibre and the intercellular space; over and above they function for quick propagation of impulse from the cell surface to the interior.
ii. Sarcoplasmic Reticulum:
This reticulum of the cardiac muscle fibre is ill developed. They are consisted of longitudinal interconnected tubules which are expanded into small terminal sacs at the Z-line. There is no well-developed transverse cisterna in the cardiac muscle (Fig. 1.68). So the transverse section of T-tubules at different regions may show triad diad (dyad) or only T-tubule depending upon the presence of sarcotubules running in association with the T-tubules.
Transmission of Impulse and Mechanism of Contraction:
The mechanism of contraction in the cardiac muscle is essentially same as that of the skeletal muscle. Impulse originated in the pace-maker area is transmitted through different conducting tissues and ultimately reaches the cardiac muscle fibre, and from which the impulse is transmitted rapidly from cell to cell through different junction surfaces of the intercalated discs. From the cell surface, the impulse is transmitted to the contractile elements of the myofibrils through the sarcotubular system.
Intercalated (Intercalary) Discs:
These are the areas of extensive cell contact and run transversely across the fibre. These also appear as dark line under the light microscope (Fig. 1.69). Electron micrograph reveals that they are made up of the unit membranes of two adjacent cells. A complex pattern of ridges and papillary projection of the unit membrane on each cell fit into corresponding grooves and pits in the other cell membrane which forms an elaborately inter digitated junction, specialized for cell-to-cell cohesion.
This interdigitated junction is mostly similar in structure with the epithelial cell junction (Fig. 1.78). In the transverse portion of the intercalated disc, there is desmosome -like cell-to cell junction with 200A intercellular cleft (Fig. 1.70). Atdesmosomes (macula adhaerentes), the inner layer of each of the opposing unit membranes is added up by a thin layer in which the myofilaments of the ajacent I- band terminate.
At irregular intervals of the transverse portion of the intercalated disc there are also small tight junctions which are known as macula occludentes. At the macula occludentes the layer of the opposing membranes are fused together by obliterating the intercellular gap. The longitudinal portion of the step- like cell to-cell junction contains the more extensive areas of close membrane contact—fasciae occludentes (intercellular space is obliterated).
These areas of the intercellular space obliteration are of low electrical resistance which helps in the rapid propagation of excitation from cell to cell throughout the whole mass of the heart and thus assisting the myocardium to behave as syncytium. The desmosomes of the transverse portion are concerned with the cell-to cell cohesion and transmission of the pull of contractile unit of one cell to the other in the longitudinal direction.
The mechanism acting behind the binding of the cells together is not yet much clear still it is evident that Ca+ has got some important role. The individual cells of cardiac muscle perfused with Ca+ free-Ringer are seen to have separated at the intercalated discs.
Electron micrography depicts that the separation takes place at the macula adhaerentes (desmosomes) where the individual unit membrane remains intact but the intercellular space is opened up. At the close junction (macula occludentes), the membrane cannot be separated due to their fusion but one of the cells may be denuded of its membrane (Fig. 1.71: b-b, c-c, d-d).
Blood Vessels, Lymphatics and Nerves of Cardiac Muscle:
Cardiac muscle fibres receive blood vessels from coronary arteries and these vessels form a basket-like capillary network around the muscle fibres. Much anastomosis between arterioles of cardiac muscles is seen. But these anastomoses are to a certain extent quite capable of supplying blood through backflow in the case of a sudden occlusion of one of vessels.
Lymphatic vessels give a rich supply to the interstitial (between cells) connective tissue. Myelinated and non-myelinated nerve fibres supply richly cardiac muscle fibres. Efferent nerve fibres form a fine network with varicose swelling and end on the surface of cardiac muscle fibres.
Metabolism of Cardiac Muscle:
Energy coefficient of the heart is being met in the form of ATP either by glycolysis or by oxidation of carbohydrate (glucose, pyruvate, and lactate) and non-carbohydrate (fatty acids, amino acids, ketone bodies). Metabolism of cardiac muscle has got similarities with those of skeletal muscle.
Through the glycolytic process (anaerobic) only 2 moles of ATP are derived, but through the oxidative process (aerobic) 39 moles of ATP are derived. Total ATP thus derived, 65% are transformed into mechanical work and the rest are dissipated as heat. So energy for mechanical work is derived mostly from oxidative process that takes place in presence of oxygen.
Cardiac muscle has got high content of myoglobin which can store sufficient quantity of oxygen and this is a great advantage of the cardiac muscle to maintain its O2 requirement during emergency. The oxidative metabolism of the cardiac muscle is altered greatly by neurohormones liberated during emotional upset or during physical and mental stress. In ischaemic heart disease where the muscle suffers from coronary insufficiency, the metabolism is affected greatly.
Metabolism of cardiac muscle can be studied by determining:
i. O2 consumption and CO2 production.
ii. Nature of substrates used up.
iii. Mechanism of oxidation.
O2 consumption of the muscle can-be assessed by determining the arteriovenous O2 difference in the blood passing through the coronary system per unit time. In isolated mammalian heart preparation the metabolism of different substrates can be studied by detailed analysis of the perfusate.
Enzymatic studies of the cardiac muscle homogenate can be made with different substrates in Warburg’s apparatus. Heart is isolated and perfused through the coronary vessels by inserting a cannula through the aorta. The perfusing fluid is forced under pressure, so that semilunar valves become closed and the fluid is forced into the coronary vessels.
1. Respiratory Quotient (R.Q):
Respiratory quotient (R.Q) of heart varies from 0.7-1.0 showing that heart muscle can utilise not only sugar but also fats and amino acids.
2. Oxygen Requirement:
The oxygen requirement of heart is much higher than that of other muscles. In exercise, it may consume about 250 ml of O2 per minute—same as that of the whole body at rest per minute. The arteriovenous difference of oxygen is nearly double (12ml).
3. Relation between O2 Consumption and Work done by Heart:
Ordinarily O2 consumption is directly proportional to the amount of work done by heart, so that it rises if the blood pressure rises. But in the intact animals increased blood pressure causes reflex cardiac slowing. In such conditions the work done by heart increases without increased oxygen consumption. In other words, the mechanical efficiency of heart rises.
In presence of O2, heart poisoned with iodo-acetate can contract for an indefinite period. In the absence of O2 heart ceases to contract after a few beats. During contraction ATP and creatine phosphate break down and supply energy. The energy is re-synthesised by the oxidation of pyruvic acid or lactic acid. In the absence of O2, latic acid is produced by glycolysis which supplies energy. In iodo-acetate poisoned cardiac muscle there is no formation of lactic acid and in the absence of O2, heart fails to contract after a few beats.
4. The Mechanical Efficiency:
The mechanical efficiency of heart is higher than that of other muscles and is about 30% (optimum). It rises with the increase of cardiac output and blood pressure up to a level. But if the heart is overworked, the efficiency falls.
5. The Carbohydrate Metabolism:
The carbohydrate metabolism of heart muscle shows a number of peculiarities, not shown by other muscles.
They are:
(a) The glycogen content of heart is about 0.6-0.7%. The amount increases in Diabetes Mellitus and also in starvation—when the glycogen content of other tissues generally falls,
(b) It can utilise glucose, lactate and pyruvate; but the last two are used in preference to the former,
(c) Cardiac muscle uses lactic acid completely. Ordinarily, no lactic acid is liberated by cardiac muscle, unless there is oxygen lack, and
(d) Probably, it indicates that heart uses glucose for the synthesis of glycogen while it derives energy by burning lactates and pyruvates.
6. Measurement of the Respiratory Quotient (R.Q.) of Heart and the Myocardial Extraction of Available Substrates:
Measurement of the respiratory quotient (R.Q.) of heart and the myocardial extraction of available substrates have clearly shown the importance of lipid as a fuel for respiration, particularly in a fasting state. The energy requirements are mainly balanced by the utilisation of carbohydrate substrates, but recently it has been suggested that the utilisation of glucose, pyruvate and lactate by the heart is influenced with coincident availability of the fatty acids and ketone bodies.
Nearly all the fatty acids which are utilised by the heart are derived from the plasma triglycerides and the albumin-bound non-esterified fatty acids (NEFA). Myocardial extractions of fatty acids are influenced by the activity of hydrolytic enzymes located at or near the cell membrane. Fatty acids supplied from circulation in excess of the needs of the heart for aerobic metabolism are deposited as tissue triglycerides and utilised subsequently as fuel for respiration.
In fasting and diabetes, energy requirements are mostly met by the heart through the oxidation of fatty acids. An adequate supply of fatty acids from circulation is ensured in these starved or diabetic conditions by the elevated levels of plasma NEFA possibly through the increased activity of lipoprotein lipase in cardiac muscle.
Lipoprotein lipase activity is reported to be increased in heart muscle and decreased in adipose tissue with starvation, diabetes and exertion. It is known that fatty acids and ketone bodies reduce glucose uptake in isolated heart and divert glucose from oxidation particularly to lactate or glycogen.
Glycogen content in the heart muscle is increased in diabetic and starved animals though the myocardial uptake and phosphorylation of glucose are reduced. It has been reported by Pandle and Morgan (1959) and Evans (1964) that fatty acids and ketone bodies inhibit the phosphofructokinase and this might account for the depression of phosphorylation of glucose and the enhancement of glycogen synthesis during starvation, diabetes, etc.
During starvation or in diabetes, there is rapid mobilisation of lipid and this state favours the easy availability of fatty acids and ketone bodies to the heart muscle. These fatty acids and ketone bodies are the common factors in inhibiting the phosphofructokinase activity.
Myocardial utilisation of pyruvate is also depressed by fatty acids and ketone bodies. It is suggested that pyruvate decarboxylation is inhibited by fatty acids or ketone bodies during starvation or in diabetes. It is postulated that most of the decarboxylase enzymes are confined to the fatty acids for entering into the TCA cycle as acetyl CoA than to the pyruvic acid.
These indicate that excess availability of circulating fatty acids diverts the decarboxylase enzymes towards the synthesis of acetyl CoA from fatty acids but not from pyruvate and maintains the TCA. On the other hand, excess pyruvate confines the decarboxylase for the synthesis of acetyl CoA.
These however suggest that respiration of fatty acids derived from circulation and also from endogenous triglycerides play an important part in regulating the cardiac metabolism of carbohydrate through inhibition of phosphofructokinase and pyruvate decarboxylase.