HEART FAILURE
MYOCARDIAL INFARCTION
General notion
Heart insufficiency develops at loading disparity on heart of it ability to execute the work, which determines by amount of blood, which comes to the heart, but by resistance to banishment of blood in aorta and pulmonary trunk. So, heart insufficiency arises, when a heart with available resistance can’t pump into artery all blood, which comes by veins.
There are three pathophysiologic heart insufficiency variants:
Heart insufficiency because of overload. The main causes are high resistance to cardiac out put, for example generall or pulmonary hypertension, heart apertures stenosis; and big diastolic blood inflow, for example atriovenous fistulas, heart values insufficiency, heavy physical work.
Heart insufficiency because of myocardium damage. All causes are divided into four groups, as following: a) infectional and toxic damages (different etiology myocarditis, alcohol myocardiopathy); b) total or local hypoxia (coronary heart disease, pneumonia, obstructive bronchitis, bronchial asthma; c) different metabolism disorders (metabolism of vitamins, carbohydrate, protein, urine acid and others), in such cases insufficiency develops even at normal or diminished heart load; d) neurotrophical and hormone abnormal influences on the heart (continuous emotional or physical stress, hyperthyreosis, hyperfunction of suprarenal glands).
Mixed heart insufficiency variant. It arises at combination of myocardium damage and its overload, for example at rheumatism, when of inflammatory myocardium damage and valvular heart violations are combined.
Stages of heart failure development
Heart failure has three stages of development: first – emergency condition, second – stable adaptation (bouth these stages display the compensation), and third – exhaustion (decompensation). If the organism or some organs need more nutritious substances and O2 the heart work is increased iorm. At myocardium damage when the normally working cardiomyocites amount is decreased and, as the result, is increased of each cardiomyocites load or in heart overflow condition heart work is provided by the alarm cardiac and extracardiac mechanisms (first stage).
Compensation mechanisms
Cardiac alarm mechanism are represented by the increase of heart beats (in two time), systolic blood ejection (to 50%), heart blood output per minute (in 4-5 time), each cardiomyocytes function and their phosphorilative potential.
Extracardial (out the heart) mechanisms are the following: the increase of O2 utilization by all tissues and as the result, arterial-venous oxygen difference of blood increases, peripheral vassal resistance is decreased.
Cardiac adaptive mechanisms is most important. The increase of heart beats number (tachycardia) provides the heart blood output constansy. It can happen in the result of raised blood pressure in right atria cavity influence on rhythm driver (sino-atrial ganglia), and also after nervous and humoral extracardial influences. Sodium and potassium ions penetration frequency (Na+ into the cells, K+out the cells) per minute is increased thus depolarization and repolarization occurs more often. Diffusion of action potentials into the sarcoplasmal reticulum membranes induces the penetration of Ca++ ions and cardiomyocites contractions.
There are two compensation mechanisms the increase of the cardiomyocytes contraction force: heterometric and homeometric.
Heterometric compensation mechanism (Franc-Starling) is inserted in blood volume overload. Heart cavities blood inflow increase during diastole, which increases of muscle fibres tension and the force of heart shortening during systole. Dilatation of heart cavities is characterized by the increase of cardiac output (it is so-called tonogenic dilatation).
Homeometric compensation mechanism works during the increase of resistance to cardiac output. Length of muscle heart fibres augments not so sharply in this case, but high pressure and effort that happened by reason of contraction of muscle at the end of diastole. Force of cardiac contractions augments not at once, but gradually with each following heart contraction, while will not arrive at level, necessary for safety of constancy of minute volume-heart. Heterometric compensation mechanism is more energy economic than homeometric. First stage doesn’t boundless because it provokes the increase of the O2 using, the decrease of diastole renewal time, myocardium rest and the decrease of hemodynamic heart characteristic: during diastole the ventricles can’t blood filling normally, a systole becomes less of full value, because of this mobilization of heterometric compensation mechanism is impossible. The first stage doesn’t boundless because there are limitary mechanisms. The increase of heart beats number and heart contraction force leads to the decrease of ATP and creatinephosphate concentration in working cardiomyocites. The glycolysis activation conduces H+ ions accumulation (lactic acid origin), which connects with troponin in place of Ca++ ions and violates actin-myosin interaction (defective systole and aqute heart insufficiency may develop).
Myocardium hypertrophy
So, in such condition another (long-time) compensatory mechanism is stimulated. The myocardium hypertrophy develops, which is characterised by heart mass increase and reinforces heart function (second stage). Long time cardiac muscle loading leads to increase of cardiomyocyte functional units loading, therefore muscular and connective cells genes are activated. Consequently, in experimental animal over little hours after constriction of aorta in heart cells appear the reinforcing signs of nuclear function, RNA synthesis augmentations and amount of rybosomes. This indicates on those albumens synthesis in myocardium cells mainly regulates by loading level. Also this process is controled by mechanisms of nevro-humoral regulation.
Myocardium hypertrophy (fig. 1) – adaptive phenomenon, directed on execution of raised work without essential loading rise of myocardium units mass. This is perfect adaptation. Consequently, sportsmen’s myocardium hypertrophy allows heart to execute great work. Nervous heart regulation also changes, that considerably broadens a diapason of its adaptation and possibility to be tolerance to long time loadings. But also at the pathological processes in the heart hypertrophy can compensate the long time violations. A hypertrophial heart differs from normal by some changed functions and structural signs, which display possibilities to overcome raised loading for a long time, and preconditions presence for beginnings of pathological changes. The heart mass increase is the result of each muscle fibre thickening, which is attended with change of intracellular structures correlation. Volume of cell augments in proportion to cub of linear dimensions, and surface – in square proportion to them, it results in cellular surface and cell mass unit proportion decrease. It’s known, that cell surface plais key role in process of cells metabolism – oxygen and nutrients using, evacuation of metabolism products, metabolism of water and electrolytes. Aggravation of myocardiocytes metabolism causes the inadequate heart muscle nutrition, especially its central departments.
A cell membrane is the place of membrane charge conduction for all tubular system and sarcoplasmatic net. Because growth of these formations at hypertrophy of muscle fibre also falls behind, thus preconditions for violation of contraction and weakening of cardiomyocytes arises. Retardation of calcium ions and their accumulation in sarcoplasma results in worse contraction. Aggravation of calcium ions come back causes inadequate cardiomiocytes relaxation. Sometimes local contracture of cardiomyocytes can arise. In case of hypertrophy cell volume increases more thauclear volume. In such case, only the linear nuclear size is increased because chromosomes count and DNA level is rised. As the nuclear role is controle of protein synthesis, and intracellular structures renewal, thus relative nuclear size reduction can cause protein synthesis violationand aggravation of cardiomiocytes nutrition. At first mitochondria mass increases more quickly, than mass of contractive proteins at hypertrophy. It causes the conditions for adequate energy provision and compensation of heart function. But then mitochondria mass begins fall down and cytoplasm mass begins increases. Mitochondria begins suffer on maximum loading, it results in their destructive changes, and their function effectiveness decrease, for example oxidative phosphorilation disturbs. This causes energy provision aggravation of hypertrophied cells. Cardiomiocytes mass increase often does not attended with adequate augmentation of capillary net, especially in cases of fast heart hypertrophy development. Big coronal arteries are also having no ability to be conformed to necessary adaptive growth. That’s why provision of hypertrophied myocardium becomes worse vascular at loading time. Disturbed structure of insertive disks and Z-lines in hypertrophied heart is broken, so electric myocardium activity changes; heart coordination contraction becomes worse in general.
A heart nervous structure is pulled in process of myocardium hypertrophy. Reinforced activity of intra- and extracardial nervous elements is observed. However, growth of nervous elements is tardier than a growth of contractive myocardium elements. Exhaustion of nervous cells takes place; trophic influences disturb, a content of norepinephrine in myocardium diminishes, it results in aggravation of contractive properties and myocardium reserves mobilization. So, a regulation of the heart functions disturbs too. A hypertrophied heart due to big mass of contractive and energy provider elements can to work adequate more time, than healthy heart, which is provided by normal metabolism. But adaptation abilities to the changes of loading and adaptative possibilities measures of hypertrophied heart are limited because functional reserve is decreased. Intracellular and extracellular structures are not balanced; it results in greater impressionability of hypertrophied heart in case of inauspicious factors influence. Long time overloading of cardiac muscles causes of functions. The main reason is contractive function disorder in the result of insufficient energy synthesis by mytochondrias and also violation of energy using by contractive fibres.
One of these pathological variants can prevail at different heart insufficiency types, for example, violation of using energy is the main one in case of long time heart hyperfunction. At the same time can appear contractive function depression common aggravation of muscle fibres relaxation, it results in local muscle contractures, and then dystrophy and death of cardimyocytes arises. Overloading distributes unevenly between different groups of muscle fibres: muscle fibres, which are more intensive worked, become weak quickly, die and substitute for connective tissue. In such case other myocardiocytes are overloaded. Connective tissue cells squeare of nearby cells, mechanical heart properties changed cause of nutrition disturbance. It is believed that normal work is impossible when replacement by connecting tissue 20-З0 % of heart mass is really. Dilatation of heart cavities can arises at distrophy of myocardium; it causes further decrease of cardiac contraction force (myogenic dilatation). In this case diastolic blood volume increases in heart cavities, and it causes the veins overflow. Raised blood pressure in right atria cavity and in cava veins straightly (by influence on sino-atria ganglia) and reflexly (Beinbrige’s reflex) causes tachycardia, which complicates violation of myocardium metabolism. That’s why heart cavities dilatation and tachycardia are the dangerous symptoms of decompensation development. Valuing biological myocardium hypertrophy sense, turn mind to internal discrepancy of given phenomenon. On one hand, this is a prettily perfect adaptative mechanism, which provides for a long time execution of raised work by heart in normal and pathological conditions, on another – structure peculiarities and functions of hypertrophied heart are by precondition for development of pathology. Dominance first or second in each concrete case determines peculiarities of pathological process.
According to metabolism, structures and myocardium functions disorders in phase of compensative heart hyperfunction there are three stages.
1. Emergency stage develops directly after heart overload, it characterizes by combination of pathological changes in myocardium (disappearance of glycogen, decrease of creatinphosphate, intracellular potassium concentration decrease and sodium one increase, stimulation of glycolysis and lactate accumulation). This stage is characterized by the fast heart mass increase (during weeks) due to protein synthesis and increase of muscle fibres thickness.
2. Stage of completed hypertrophy and steady hyperfunction. In this stage myocardium mass is increased on 100 – 120 % and couldn’t longer increases. Metabolism and structures of myocardium is normal; oxygen consumption, energy synthezise, macroergic substances contents does not differ from norm, blod flow is normalized. A hypertrophic heart is adaptated to new loading conditions.
3. Stage of gradual exhaustion of the heart and progressing of cardiosclerosis is characterized by deep disorder of metabolism and structures in power-creating and contractive elements of myocardium. Part of myocardiocytes dies and replaces by connective tissue. Heart regularly apparatus is disturbed. Progressing of compensatory mechanisms exhaustion leads to chronic heart insufficiency development, and then to the blood circulation insufficiency (fig. 2).
Chronic heart insufficiency
Chronic, or stagnant, heart insufficiency develops gradually, mainly by reason of metabolic violations in myocardium at long time heart hyperfunction or at different kinds of myocardium injury appearances. Because heart output is decreased, blood supply of organs, which are localized on heart outflow ways, diminishes. At the same time by reason of heart inability to pump all blood that comes to it stagnation on blood inflow ways develops (in veins). As volume of venous channel approximately in 10 times exceeds an arterial channel volume, a considerable amount of blood nuddle together in veins. Blood insufficiency acquires some specific signs in case of work violation mainly some heart ventricle circulation and is called by insufficiency of left-ventricle type or right-ventricle one. In first case blood stagnation is observed in veins of small blood circulation, that can to be reason of lungs edema, in second case – in veins of big blood circulation, in such case liver is enlarged, the edema of legs and ascites appears. Violation of contractive myocardium function does not at once causes development of the blood circulation insufficiency.
As adaptive mechanism at first peripheral arterioles resistance of big blood circulation reflexly decreases, that relieves a blood flow to majority of organs. Arterioles of small blood circulation reflexly narrow, thus to left atria blood inflow diminishes and at the same time pressure in system of pulmonary capillaries decreases. Last mechanism is the pulmonary capillaries protection from overflow of the blood and it prevents of lungs edema development. There is typical some function discord sequence of different heart departments. Consequently, decompensation of strong left ventricle functions quickly causes violation of left atria function, blood stagnation in small blood circulation and constriction of pulmonary аrteriole but then a less stronger right ventricle is overloaden, that leads to its decompensation and development of the right-ventricle type insufficiency.
Hemodynamic indexes of chronic heart insufficiency change like so: heart volume per minute decreases (from 5-5,5 to 3-4 l/min); speed of blood stream decreases in 2-4 times; arterial pressure changes a little; venous pressure rises; the capillaries and postcapillares vein are dilated; a blood stream slows; pressure rises. The pathological changes of other organs, which arise later, are the result of prescribed changes.
Retardation of blood stream in big blood circulation system and violation of the lung blood circulationin causes increase of renewed hemoglobin amount in blood. Skin and mucous membranes have a typical blue colour (cyanosys). Tissues have no adequate quantity of oxygen. Hypoxia is characterized by accumulation of organic acids and CO2 that leads to acidosis development. Acidosis and hypoxia result in violation of breathing regulation and causes dyspnoea. Erythropoiesis is stimulated, general volume of circulatory blood and relative contents of blood cells is increased too, and all these changes display of hypoxia compensation, but in same time are the reasen of blood viscosity increase and violation of blood hemodinamic properties.
By reason of high pressure in capillaries and tissue acidosis an edema develops, which, into its turn, reinforces hypoxia, because diffuse way from capillary to cell is increased. The general violations of water and electrolytes metabolism (sodium and water accumulation) streingthen stagnant edema. This is one more proof of internal compensation mechanisms contradictions during pathological process. Mechanisms, which evolutional happened for guaranteeing of salts and liquid sufficient contentsfin organism in case of water loss and blood loss complicates of patient condition in case of heart insufficiency. Surplus of common used in patients’ blood, which have heart insufficiency, does not excret by kidneys like in healthy man, and accumulates in organism together with equivalent water volume.
Violation of tissues nutrition at long time of the blood supply insufficiency causes deep and inconvertible disorder of intracellular metabolism. It results in violation of protein synthesis, especially ensime of respiratory metabolism ways, in development of histotoxic type of hypoxia. These phenomena are typical for terminal phase of circulatory insufficiency. Blood flow insufficiency in digestive tract causes terrible exhaustion of the organism, so – called cardiac cachexia.
Pathophysiological mechanism of heart insufficiency another origin is ardiomyocites damage. It can be result of inflammation or dystrophy, genetic defects, infection, intoxication or immunopathological processes, illnesses, which cause myocardium hypoxia or metabolism violations (protein, lipid, mineral and vitamin). Uneffective ATP synthezise or ATP using by cardiomyocytes can be really. Processes of uneffective ATP synthezise arises in case of oxygen in come insufficient to the cardiomyocyte, O2 concentration decrease or ischemia, and also at violation of oxidative substances in come, uneffective mitochondrias functions, creatinekinase – creatinephosphate system system violation. Uneffective ATP using arises in case of myofibril proteins and sarcoplasmal net damage and at disorder of calcium ions, potassium, and sodium metabolism. Violation of cardiomyocytes membrane structures by lipid peroxides, by free radicals and hydroperoxyde can be one of damage mechanisms. Free radical oxidation can be result of oxidative metabolism violation cardiomyocyte or antioxidant systems insufficiency. First functions of specific membrane pumps (Na+, К+–АТP-ase, Са++–АТP-ase) disturb, than gradually membrane penetrability and membrane phospholipid damage arises. Violation of membrane results in change of sodium, potassium, chlorine ions and water stream. It causes swelling of cell, and calcium ions accumulation and development of calcium toxic effects. It is possible the increase of α– and β– adrenoreceptors amount and free catecholamine concentration, that deepens a primary damage. In case of metabolism violations, which turned in extremely long ways, death of cardiomyocytes is possible (fig. 3, 4). The number of working cardiomyocytes decreases and it leads to their overload, thus mechanisms of compensations are the same as earlier prescribed.
Coronary heart disease
The notion of coronary heart disease (CHD), also called coronary artery disease, describes chronic or acute heart disease caused by impaired coronary blood flow in the result of coronary artery pathology. Disease of the coronary vessels can cause angina, myocardial infarction, cardiac dysrhythmias, conduction defects, heart failure, and sudden death.
Classification of coronary heart disease
There are 4 main types clinical manifestations of coronary heart disease.
1. Stenocardia (angina pectoris)
a) Stenocardia of the stress;
b) Stenocardia of the rest
2. Myocardial infarction
3. Intermediate variants
a) Acute focal myocardial dystrophy;
b) Small focal myocardial infarction
4. Indolence CHD
a) Silent (asymptomatic) CHD;
b) Atherosclerotical cardiosclerosis
Etiology of coronary heart disease
During CHD can be affected one or all of the major epicardial coronary arteries and their branches and can be diffuse or localized to one area of a single vessel. The main reason of the vessels injury is atherosclerosis that reduces blood flow.
Risk factors of the CHD are hypercholesterinemia, arterial hypertension, smoking (especially for women), hypokinesia, obesity, old age, and mail sex.
Atherosclerosis causes narrowing of the coronary arteries. Metabolic demands of the heart are increased with everyday activities such as mental stress, exercises, and exposure to cold. In certain disease states, such as thyrotoxicosis, the metabolic demands may be so excessive that blood supply is inadequate despite normal coronary arteries. In other situations, such as aortic stenosis, the coronary arteries may not be diseased, but the perfusion pressure may be insufficient to provide adequate blood flow. Symptomatic myocardial ischemia (angina pectoris) and silent, or painless, myocardial ischemia are important functional indicators of active CHD and increased risk of myocardial infarction or sudden death. The term angina pectoris is derived from a Latin word meaning to choke. Angina pectoris (stenocardia) is a symptomatic paroxysmal chest pain or pressure sensation associated with transient myocardial ischemia. The pain typically is described as constricting, squeezing, or suffocating. It usually is steady, increasing in intensity only at the onset and end of the attack. The pain of angina commonly is located in the precordial or substernal area of the chest; it is similar to myocardial infarction in that it may radiate to the left shoulder, jaw, arm, or other areas of the chest (in some persons may be epigastric pain).
Stenocardia. Classic angina, sometimes-called exertion angina is associated with atherosclerotic (fig. 5) disease that produces fixed obstruction of the coronary arteries. It occurs when the metabolic needs of the myocardium exceed the ability of the occluded coronary arteries to deliver adequate blood flow during physical exertion, emotional stress, or exposure to cold. The adrenalin blood concentration in such conditions increases, so rate and force of the heart contractions and O2 need increase too. Adequate dilation of the heart vessels is impossible in the condition when coronary arteries are inelastic. Adrenalin excess violates cardiomyocytes metabolism and electrolyte balance.
The syndrome of variant angina or Prinzmetal’s angina was first described Prinzmetal. It is caused by spasm of the coronary arteries; this condition is also called vasospastic angina. Unlike the classic form of angina, which occurs with exertion or stress, variant angina usually occurs during rest, smoking or with minimal exercises, and frequently occurs nocturnally. The mechanism of coronary vasospasm is uncertain. It may be the result of hyperactive sympathetic nervous system responses, the result of calcium metabolism defect in vascular smooth muscle, or the result of reduced syntheziseof prostaglandin I2 or NO, which promotes vasodilation. Arrhythmias often occur when the pain is severe; ECG changes include ST segment elevation or depression, T- wave peaking, rhythm disturbances.
Unstable angina is the result of atherosclerotic plaque disruption. Because of its propensity to lead to infarction, it is some times referred to as preinfarction angina. Plaque disruption may occur with or without thrombosis, it increases the degree of coronary artery obstruction. When the plaque injury is mild, intermittent thrombotic occlusion may occur and cause episodes of anginal pain at rest. Vasoconstricting factors (thromboxane, serotonin, and platelet-derived growth factor) are released from platelets that aggregate at the site of injury. These platelet factors contribute, even at rest, to episodes of reduced coronary blood flow and silent or symptomatic myocardial ischemia. Thrombus formation can progress until the coronary artery becomes occluded, leading to myocardial infarction.
Silent myocardial ischemia occurs in the absence of anginal pain. The factors that cause silent myocardial ischemia appear the same – impaired blood flow in the result of coronary atherosclerosis or vasospasm. The reason for the painless episodes of ischemia is unclear. The episodes may be shorter and involve less myocardial tissue than those producing pain. Another explanation is that persons with silent angina have defects in pain threshold, pain transmission, or automatic neuropathy with sensory denervation. There is evidence of an increased incidence of silent myocardial ischemia in person with diabetes mellitus, probably the result of autonomic neuropathy, which is a common complication of diabetes.
Myocardial infarction.
Myocardial infarction is ichemical necrosis of the myocardium that develops in the result of sharp decrease or stop blood flow through some area of the heart. Now, it is the most prevalent disease in the world, number patients, which suffer myocardial infarction increase.
Etiology of myocardial infarction
The main reason of myocardial infarction is atherosclerosis of the coronary arteries (fig. 6). The main proves are the results of pathological anatomy dissection of the body patients with myocardial infarction, which died. Atherosclerotical plaques on the coronary artery wall were discovered in 90-95 % cases. Acute myocardial infarction may be the result of rupture or fissuring of an atherosclerotical plaque and thrombus formation that interrupts blood flow. Some time it is the result of thrombembolism or prolonged severe vasospasm, as in Prinzmetal’s variant angina.
Risk factors.
1. Stress. Emotional or physical stress stimulates sympathetic link of the vegetative nervous system and hypothalamus-hypophysis-suprarenal system. Adrenalin stimulates β-adrenoreceptor-mediated functions of the sympathetic nervous system. Heart work, its metabolism and O2 need increase. But atherosclerotical plaque results vessel diameter narrowing and reduces the coronary arteries ability to dilate. All these cause acute blood flow insufficiency and ischemia.
2. Age. Most often myocardial infarction happened in person 40-59 years old.
3. Mail sex. Men are ill myocardial infarction in 2-3 time frequently then women and die in 3-4 time more often. It difference is the result of many factors. Atherosclerosis develops in men earlier then in women because after birth men have thicker intima then women. Women are more adapted to hypoxia; it is the result of periodic menstrual blood loss. Men have trunk type of heart arteries anatomy, but women have ramified vessels and many anastomoses. Estrogens have protective properties as antioxidants.
4. Arterial hypertension. The high arterial pressure causes the increase of heart work and O2 requirement, besides it accelerates the atherosclerosis development and violation of the heart blood perfusion. Arterial hypertension causes myocardium hypertrophy, which decreases of the vessels number in volume unit. It leads to blood flow insufficiency and hypoxia. Hypertonic crisis (sharp arterial hypertension) is very dangerous because it very increases peripheral vessel resistance, cardiac output, heart work and especially O2 need (remind about vessel diameter narrowing and reduces the coronary arteries ability to dilate) and acute ischemia.
5. Diabetes mellitus is complicated by atherosclerosis (so-called macroangiopathy). It results from hyperlipoproteinemia.
Pathogenesis of myocardial infarction
All mechanisms of myocardial infarction beginning can be divided in two groups: first group mechanisms (start mechanisms) provoke acute myocardial ischemia in the result of blood flow violation and second group includes mechanisms of myocardium necrosis.
Mechanisms of acute myocardial ischemia. Growing up of atherosclerotical plaque decreases coronary artery diameter, violates blood flow through same area of the heart, especially in left ventricle, complicates myocardium nutrition and may cause development so-called critical stenosis and necrosogenic ATP deficiency. Atherosclerotical injury of vessel strengthens its sensitivity to vasospastic influences. It results from violation of NO (vasodilation agent) synthesis by endotoliocytes because NO-synthase activity in such vessel is very decreased. Atherosclerotical vessel injury reduces anticoagulative blood properties because heparin concentration is decreased. This substance is used for lipoproteinlipase activation in hyperlipoproteinemia condition (it is the main risk factor of atherosclerosis), besides injured vessel has reduced antithrombotic potential (antithrombin III deficit), unmasked collagen fibers and fibronectin cause thrombocytes activation, their adhesion, aggregation and then thrombin formation. It is the resultant thrombus that interrupts blood flow. All these mechanisms lead to development of acute myocardial ischemia and onset the mechanisms of myocardiocytes necrosis ().
Mechanisms of myocardium necrosis. Acute ischemia causes deficiency of the energy substances supply (adenosinthreephosphate, creatinphosphate). It results from the decrease of cytochromoxydase activity. Electrons transposition violates and it very reduces Crebs cycle activity. Cardiomyocytes use adenosinthreephosphate and creatinphosphate but restoring of their concentration is inadequate. ADP, AMP, adenosine and inorganic phosphate are accumulated in cardiomyocytes. Energy deficit leads to oppression of Na,K-ATPase and Ca-ATPase activity. Insufficiency of Na,K-ATPase activity causes violation of repolarization, Na+ accumulates in the myocardiocytes, myocardium becomes electrically unstabilized and inhomogeneous. These changes contribute to cardiac fatal arrhythmias and sudden death, usually as the result of ventricular fibrillation. During the period of impaired blood flow, injured and ischemic cells revert to anaerobic metabolism, with accumulation of organic acids (especially lactic), much of which is released into the local extracelullar fluid. The necrotic cells become electrically inactive, and their membranes become disrupted, such that their intracellular contents, including potassium, are released into the surrounding extracellular fluid. This causes local areas of hyperkalemia, which can affect the membrane potentials of functioning myocardial cells. As a result of membrane injury and local changes in extracellular potassium and pH levels, some parts of the infracted myocardium are unable to conduct or generate impulses, other areas are more difficult to excite, and still others are overly excitable. These different levels of membrane excitability in the necrotic, injured, and ischemic zones of the infracted area set the stage for development of dysrhythmias and conduction defects after myocardial infarction. Each of these zones in the infracted area conducts impulses differently. Typical ECG changes associated with death of myocardial tissue include prolongation of Q wave, elevation of the ST segment, and inversion of the T wave. Ca2+ accumulation results from Ca-ATPase activity oppression, it contributes to cardiomyocytes contracture (cardiomyocytes caot relax), and mitochondriaes damage (Ca2+ excess can be accumulated in mitochondriaes) that make worse energy deficit. Because many enzymes are blocked, Crebs cycle violation leads to accumulation of acetylcoensim A and fat acids. Fat acids oxidation in the β-cycle is impossible because this cycle needs ATP, so concentration of fat acids in cardiomyocytes increases. These substances have ability to dissolve membrane lipids and contribute to damage membrane ion channels. The principal biochemical consequence of acute myocardial infarction is the onset of anaerobic metabolism with inadequate production of energy to sustaiormal myocardial function. As a result, a striking loss of contractile function occurs within 60 seconds of acute myocardial infarction onset. It results from H+ ions accumulation (metabolic acidosis develops). Lactic and piruvate acids accumulation causes depress of creatinkinase activity, this enzyme controls phosphates delivery to myofibrils. Besides, H+ ions obstruct Ca2+-troponin interaction, so actin-myosin interaction is impossible in this condition, all these depress of myocardiocytes contractile function. Phosphates accumulation, which results from macroergic substances breakup, causes insoluble calcium phosphate salt forming and then calcium ions concentration decrease in myocardiocytes. Some time “reperfusion syndrome” (term reperfusion refers to reestablishment of blood flow in ischemic area) results from the primary decrease of calcium ions concentration. This phenomenon is characterized by the repeat damage of myocardiocytes in the result of rapid come in myocardiocytes Ca2+ ions because big gradient concentration of calcium between blood and heart tissue in zone of ischemia. This paradox arises at stress, during surgical treatment of coronary artery occlusion or thrombolytic therapy. Calcium and catecholanimes cause phospholipases activation; ischemia stimulates lipid peroxidation and exhausts antioxidation system of the membrane protection. All these impair membranes, violates membrane ion channels. Lysosomal membrane damage leads to development myocardiocytes autolysis (it is necrosis which results from action own cell enzymes). Myocardial cells necrosis (fig. 8) causes release of different myocardiocytes components that appear in the blood and are the diagnostic markers (myoglobin, creatine kinase, lactate dehydrogenase, and troponin).
Early reperfusion (within 15 to 20 minutes) after onset of ischemia can prevent necrosis. Reperfusion after a longer interval can salvage some of the myocardial cells that would have died owing to longer periods of ischemia. It may also prevent microvascular injury that occurs over a longer period. Although much of the viable myocardium existing at the time of reflow ultimately recovers, critical abnormalities in biochemical function may persist, causing impaired ventricular function. The recovering area of the heart is often referred to as stunned myocardium. Because myocardial function is lost before cell death occurs, a stunned myocardium may not be capable of sustaining life, and persons with large areas of dysfunctional myocardium may require life support until the stunned regions regain their function.
A myocardial infarct may involve the endocardium, myocardium, epicardium, or a combination of these. Acute myocardial infarction can be divided into two major types: transmural and subendocardial infarcts. Transmural infarcts involve the full thickness of the ventricular wall and most commonly occur when there is obstruction of a single artery. Subendocardial infarcts involve the inner one third to one half of the ventricular wall and occur more frequently in the presence of severely narrowed but still patent arteries.
Although gross tissue changes are not apparent for hours after onset of an acute myocardial infarction, the ischemic area ceases to function within a matter of minutes, and irreversible damage to cell occurs in about 40 minutes. The principal biochemical consequence of acute myocardial infarction is the onset of anaerobic metabolism with inadequate production of energy to sustaiormal myocardial function. As the result, a striking loss of contractile function occurs within 60 seconds of acute myocardial infarction onset. Changes in cell structure (glycogen depletion and mitochondrial swelling) develop within several minutes. These early changes are reversible if blood flow is restored. Irreversible myocardial cell death occurs after 20 to 40 minutes of severe ischemia. Microvascular injury occurs in about 1 hour and follows irreversible cell injury. If blood flow can be restored within this 20- to 40-minute timeframe, loss of cell viability does not occur or is minimal. The progression of ischemic necrosis usually begins in the subendocardial area of the heart and extends through the myocardium to involve progressively more of the transmural thickness of the ischemic zone. The extent of the infarct depends on the location, rapidity of development, severity of coronary vessel occlusion and vasospasm, amount of heart tissue supplied by the vessel, duration of the occlusion, metabolic needs of the affected tissue, extent of collateral circulation, and other factors such as heart rate, blood pressure.
Myocardial cells that undergone necrosis are gradually replaced with scar tissue. An acute inflammatory response develops in the area of necrosis about 2 to 3 days after infarction. Macrophages begin removing the necrotic tissue, they stimulate fibroblasts proliferate activity and their ability of collagen fibrous synthesis; the damaged area is gradually replaced with an ingrowth of highly vascularised granulation tissue, which gradually becomes less vascular and more fibrous.
The stages of recovery from acute myocardial infarction are closely related to the size of the infarct and the changes that have taken place within the infracted area. Fibrous scar tissue lacks the contractile, elastic, and conductive properties of normal myocardial cells; the residual effects and the complications are determined essentially by the extent and location of the injury.
Complications of acute myocardial infarction
Among the are sudden death, heart failure and cardiogenic shock, pericarditis and Dressler’s syndrome, thrombemboli, rupture of the heart, and ventricular aneurysms.
Sudden death from coronary heart disease is death that occurs within 1 hour of symptom onset. It usually is attributed to fatal dysrhythmias, which may occur without evidence of infarction. About 30 % to 50 % of persons with acute myocardial infarction die of ventricular fibrillation within the first few hours after symptoms begin. Depending on its severity, myocardial infarction has the potential for compromising the pumping action of the heart. Heart failure and cardiogenic shock are dreaded complications. Cardiogenic shock is characterized by the failure to eject blood from the heart, hypotension, and inadequate cardiac output. Increased systemic vascular resistance often contributes to the deterioration of cardiac function by increasing afterload or the resistance to ventricular systole. The filling pressure, or preload of the heart, is also increased as blood returning to the heart is added to blood that was previously returned but not pumped forward, resulting in an increase of end-systolic ventricular volume. Increased resistance to ventricular systole (afterload) combined with the decreased myocardial contractility causes the increased end-systolic ventricular volume and increased preload, which further complicate cardiac status.
Pericarditis may complicate the course of acute myocardial infarction. It usually appears on the second or third day after infarction. The person experiences a new type of pain that is sharp and stabbing and is aggravated with deep inspiration and positional changes. Dressler’s syndrome describes the sings and symptoms associated with pericarditis, pleurisy, and pneumonitis: fever, chest pain, dyspnea, and abnormal laboratory test results (elevated leucocytes count and sedimentation rate). The symptoms are the result of hypersensitivity response to tissue necrosis (hyperergic inflammation), so anti-inflammatory agents or corticosteroid drugs may be used to reduce the inflammatory response.
The acute post myocardial infarction period can be complicated by rupture of the myocardium, the interventricular septum, or a papillary muscle. Myocardial rupture, occurring on the fourth to seventh day when the injured ventricular tissue is soft and weak, often is fatal. Necrosis of the septal wall or papillary muscle may also lead to the rupture of either of the structures, which worsening of ventricular performance. An aneurysm is an out pouching of the ventricular wall. Scar tissue does not have the characteristics of normal myocardial tissue; when a large section of ventricular muscle is replaced by scar tissue, an aneurysm may develop. This section of the myocardium does not contract with the rest of the ventricle during systole. Instead, it diminishes the pumping efficiency of the heart and increases the work of the left ventricle, predisposing the patient to heart failure. Ischemia in the surrounding area predisposes the patient to development of dysrhythmias, and stasis of blood within the aneurysm can lead to thrombus formation.
