Six Types of Cardiovascular Disease

Cardiovascular disease is a term that refers to more than one disease of the circulatory system including the heart and blood vessels, whether the blood vessels are affecting the lungs, the brain, kidneys or other parts of the body. Cardiovascular diseases are the leading cause of death in adult Canadian men and women. The following six types of cardiovascular disease are highlighted below: 1. Ischemic heart disease is the most common type of cardiovascular disease in Canada and other industrialized countries around the world. It refers to problems with the circulation of blood to the heart muscle. A partial blockage of one or more of the coronary arteries can result in a lack of enough oxygenated blood (ischemia) thus causing symptoms such as angina (chest pain) and dyspnea (shortness of breath). A complete blockage of an artery causes necrosis (damage to the tissues) or a myocardial infarction, commonly known as a heart attack. How do I know if I'm having a heart attack? What is angina?

2. Cerebrovascular disease (Stroke) refers to a problem with the circulation of blood in the blood vessels of the brain. A blockage with effects lasting less than 24 hours is referred to as a transient ischemic attack. A complete blockage with long-term effects is referred to as a cerebrovascular thrombosis (clot) or accident or a stroke. Sometimes, a blood vessel in the brain can burst resulting in long term effects. Stroke Information

3. Peripheral vascular disease affects the circulation primarily in the legs]. Patients with this disease typically complain of pain in their calves especially when walking. 4. Heart failure occurs when the pumping action of the heart cannot provide enough blood to the rest of the body as it is needed. This can happen as a result of damage to the heart muscle, for example from a heart attack, or from excessive consumption of alcohol, or because of a heart muscle disease also called a cardiomyopathy. Patients with heart failure usually suffer from shortness of breath and swelling of the legs. 5. Rheumatic heart disease once common in Canada is a major problem in many poor countries. This disease begins with a bacterial infection in childhood, affecting joints and heart valves. The heart problems appear many years later. Often the valves have to be replaced by an operation. Other infections can occur attacking the inner tissues of the heart including the valves (endocarditis) and the outer tissue overlying the heart (pericarditis).

6. Congenital heart disease is a problem with the structure of the heart arising because of a birth defect. These anatomical defects can be as simple as a small hole in one of the inside walls of the heart or they can be very complex, affecting the way blood flows through the heart and lungs. Some congenital heart problems result in death unless immediately corrected by surgical intervention. Others cause disability to varying degrees and are treated by surgery later in life with correction of the problem sometimes requiring more than a single operation.

Cardiovascular Diseases

What are Cardiovascular Diseases?

Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the heart or blood vessels (arteries and veins). Cardiovascular disease is the number one cause of death and disability in the United States and most European countries. A definition of cardiovascular disease doesn't include an age. In fact, early signs of cardiovascular disease have been noted during surgeries performed on young soldiers wounded in battle. It has been estimated that plaque build-up was seen in the arteries of nearly 90% of the troops wounded in Vietnam. That's pretty amazing when one considers that these soldiers were in their teens and early twenties. So, we need to take a good look at exactly what cardiovascular disease is, what causes it, and how we can prevent it. The term 'cardiovascular disease' is used to cover a group of problems related to the heart or the body's overall circulatory system. These problems include heart attacks, strokes, arrythmias, congestive heart failure, ischemia, hypertension, angina, and other dysfunctions. For the sake of brevity, this article will focus on heart disease and its prevention. The reason for concentrating on heart disease is simple. Someone in the United States dies every minute from a heart attack. Cardiovascular disease is the number one health problem in Western society. It is the leading cause of death for over one million people each year in the United States. It is estimated that over 50 million Americans currently have cardiovascular disease although many will not know it because they have no symptoms yet. In fact, 25% of the people who have heart attacks had no symptoms prior to the incident. Following cigarette smoking, the major factor that contributes to heart disease is one's diet. There are several dietary changes that can help prevent the onset of heart disease. Start by eating less red meat and dairy products. For protein, you can eat fish, skinless chicken and turkey. Avoid tobacco, alcohol, chocolate, sugar, fatty foods, fried foods, spicy foods, soft drinks, and all processed foods such as white bread. Make sure that you get enough essential fatty acids, particularly omega 3. Eating fish provides the availability of omega-6 and omega-3 fatty acids, a low fat-to-protein ratio, and a high mineral content, particularly in ocean fish. The beneficial fats may help prevent cardiovascular disease. A high fiber content in your diet is helpful. Eating lots of raw foods such as salads, fruits, and vegetables supplies an adequate level of fiber. Cooking tends to break down the fiber of most foods.

Low sodium diets are beneficial in preventing heart disease. Eliminate foods that are high in salt content. Some foods and additives to avoid include foods with preservatives or mold inhibitors, canned vegetables, diet soft drinks, meat tenderizers, commercially prepared foods, MSG, Saccharin, and baking soda. Studies have shown that there are several nutritional supplements that can be helpful in heart disease prevention. As in the case of the herbs, each of these supplements has its own properties and each one can have severe side effects if taken inappropriately. The heart-helping supplements are coenzyme Q10, calcium, magnesium, L-carnitine, lecithin, potassium, selenium, vitamin E, essential fatty acids, copper, multienzyme complex, bromelain, vitamin B complex, vitamin C. Perhaps the biggest risk factor of all in heart disease is lifestyle. That means that heart attacks and heart disease are very preventable. It just takes a little work, like everything worthwhile in life does. The key lifestyle changes that will help keep your heart healthy are things that we all know to do. It's interesting to see that a lot of these risk factors work off of each other. For example, losing weight will usually lower your cholesterol and blood pressure. The best changes to make for preventing heart disease are:

Quit smoking. Lose weight. Lower your cholesterol. Lower your blood pressure. Reduce stress. Exercise regularly. One last bit of information that I thought might be helpful is a list of terms that you might hear in the discussion of heart disease. It's always better to know what your doctor is describing and the definitions below can help you with that. Common Heart Disease Terms Angina - a sense of suffocating contraction or tightening of the lower part of the chest. Arrhythmia - an irregularity in the force or rhythm of the heartbeat. Atherosclerosis - a form of arteriosclerosis characterized by the deposition of plaques containing cholesterol and lipids on the innermost layer of the walls of large and medium-sized arteries. Arteriosclerosis - a chronic disease in which thickening, hardening, and loss of elasticity of the arterial walls result in impaired blood circulation. It develops with aging, and in hypertension, diabetes, and other conditions.

Atrium - either of the upper chambers of the heart that receives blood from the veins and forces it into a ventricle. Cardiomyopathy - a disease or disorder of the heart muscle, especially of unknown or obscure cause. Congestive Heart Failure - a condition marked by weakness, edema, and shortness of breath that is caused by the inability of the heart to maintain adequate blood circulation in the peripheral tissues and the lungs. Coronary - the blood vessels surrounding the heart or an obstruction of blood flow in a coronary artery by a blood clot. Fibrillation - rapid uncoordinated twitching movements that replace the normal rhythmic contraction of the heart and may cause a lack of circulation and pulse. Hypertension - arterial disease in which chronic high blood pressure is the primary symptom. Ischemia - a decrease in the blood supply to a bodily organ, tissue, or part caused by constriction or obstruction of the blood vessels. Mitral Valve Prolapse - a condition resulting from the mitral valve not regulating the flow of blood between the left atrium and left ventricle of the heart. Myocardial Infarction - destruction of heart tissue resulting from obstruction of the blood supply to the heart muscle. Palpitations - irregular, rapid beating or pulsation of the heart. Peripheral Vascular Disease - a condition involving circulatory problems in the extremities. Stroke - a sudden loss of brain function caused by a blockage or rupture of a blood vessel to the brain. Tachycardia - a rapid heart rate, especially one above 100 beats per minute in an adult. Ventricle - a.) the chamber on the left side of the heart that receives arterial blood from the left atrium and contracts to force it into the aorta. b.) the chamber on the right side of the heart that receives venous blood from the right atrium and forces it into the pulmonary artery. By the time that heart problems are detected, the underlying cause (atherosclerosis) is usually quite advanced, having progressed for decades. There is therefore increased

emphasis on preventing atherosclerosis by modifying risk factors, such as healthy eating, exercise and avoidance of smoking.

PATHOPHYSIOLOGY OF CARDIOVASCULAR SYSTEM PATHOPHYSIOLOGY OF VASCULAR TONE Arterial hypertension is the leading cause of death in the world and the most common cause for an outpatient visit to a physician; it is the most easily recognized treatable risk factor for stroke, myocardial infarction, heart failure, peripheral vascular disease, aortic dissection, atrial fibrillation, and end-stage kidney disease. Despite this knowledge and unequivocal scientific proof that treatment of hypertension can prevent many of its life-altering complications, hypertension remains untreated or undertreated in the majority of affected individuals in all countries, including those with the most advanced systems of medical care. Inadequate treatment of hypertension is a major factor contributing to some of the adverse secular trends since the early 1990s, including an increased incidence of stroke, heart failure, and kidney failure plus a leveling off of the decline in coronary heart disease mortality. The World Health Organisation (WHO) has proposed the following values for all age groups (mmHg/7.5 = kPa):
Normal Threshold hypertension Hypertension

diastolic pressure (Pd [mmHg]) systolic pressure (Ps [mmHg])

<90

90 95

>95

<140

140160

>160

Arterial hypertension, defined as a systolic blood pressure (SBP) in excess of 140 mm Hg and/or diastolic blood pressure (DBP) in excess of 90 mm Hg, has long been identified as an independent risk factor for cardiovascular disease. Traditionally, emphasis has been placed on elevated DBP as a risk factor for the

development of target organ damage. However, as early as 1971, the Framingham study showed that, although DBP was a major determinant of cardiovascular risk in men under 45 years of age, SBP was the stronger risk factor in older men and in women of all ages. Since then, several observational studies have suggested that the pulse pressure (PP) may be a better predictor of cardiovascular complications than SBP or mean arterial pressure.

Hypertension commonly is divided into the categories of primary and secondary hypertension. In primary, or essential, hypertension, which accounts for 90% to 95% of all hypertension, the chronic elevation in blood pressure occurs without evidence of other disease. In secondary hypertension, the elevation of blood pressure results from some other disorder, such as kidney disease. Malignant hypertension, as the name implies, is an accelerated form of hypertension. Etiology and pathogenesis of essential arterial hypertension

Several factors, including hemodynamic, neural, humoral, and renal mechanisms, are thought to interact in producing long-term elevations in blood pressure. As with other disease conditions, it is probable that there is not a single cause of essential hypertension or that the condition is a single disease. Because arterial blood pressure is the product of cardiac output and peripheral vascular resistance, all forms of hypertension involve hemodynamic mechanismsan increase in either cardiac output or peripheral vascular resistance, or a combination of the two. Other factors, such as sympathetic nervous system activity, kidney function in terms of salt and water retention, the electrolyte composition of the intracellular and extracellular fluids, and humoral influences such as the renin-angiotensin-aldosterone mechanism, play an active or permissive role in regulating the hemodynamic mechanisms that control blood pressure.

Mechanisms of the development of Hypertension

The product of cardiac output (= stroke volume [SV] heart rate) and total peripheral resistance (TPR) determines blood pressure (Ohms law). H. thus develops after an increase in cardiac output or TPR, or both. In the former case one speaks of hyperdynamic H. or cardiac output H., with the increase in PS being much greater than that in PD. In resistance H., PS and PD are either both increased by the same amount or (more frequently) PD more than PS. The latter is the case when the increased TPR delays ejection of the stroke volume. The increase of cardiac output in hyperdynamic hypertension is due to an increase in either heart rate or extracellular volume, leading to an increased venous return and thus an increased stroke volume (FrankStarling mechanism). Similarly, an increase in sympathetic activity of central nervous system origin and/or raised responsiveness to catecholamines (e.g., caused by cortisol or thyroid hormone) can cause an increase in cardiac output. Resistance hypertension is caused mainly by abnormally high peripheral vasoconstriction (arterioles) or some other narrowing of peripheral vessels, but may also be due to an increased blood viscosity (increased hematocrit). Vasoconstriction mainly results from increased sympathetic activity (of nervous or adrenal medullary origin), raised responsiveness to catecholamines, or an increased concentration of angiotensin II. Autoregulatory mechanisms also include vasoconstriction. If, for example, blood pressure is increased by a rise in cardiac output, various organs (e.g., kidneys, gastrointestinal tract) protect themselves against this high pressure. This is responsible for the frequently present vasoconstrictor component in hyperdynamic H. that may then be transformed into resistance H. Additionally, there will be hypertrophy of the vasoconstrictor musculature. Finally, H. will cause vascular damage that will increase TPR (fixation of the H.). Some of the causes of hypertension are known (e.g., renal or hormonal abnormalities), but these forms make up only about 5 10 % of all cases. In all others the diagnosis by exclusion is primary or essential hypertension. Apart from a genetic component, more women than men and more urbanites than country dwellers are affected by primary H.

In addition, chronic psychological stress, be it job-related (pilot, bus driver) or personality-based (e.g., frustrated fighter type), can induce hypertension. Especially in salt-sensitive people (ca.1 3 of patients with primary H.; increased incidence when there is a family history) the high NaCl intake (ca. 10 15 g/d= 170 250 mmol/d) in the western industrialized countries might play an important role. While the organism is well protected against Na+ loss (or diminished extracellular volume) through an increase in aldosterone, those with an increased salt sensitivity are apparently relatively unprotected against a high NaCl intake. In these patients, aldosterone release is so strongly inhibited even at normal Na+ intake (> 100 mmol/d) that it cannot be lowered any further. A diet with low NaCl intake would in this case bring NaCl balance into the aldosterone regulatory range. The actual connection between NaCl sensitivity and primary H. has not been fully elucidated, but the possibility is being considered that responsiveness to catecholamines is raised in people sensitive to NaCl. This results, for example, on psychological stress, in a greater than normal rise in blood pressure, on the one hand, due directly to the effect of increased cardiac stimulation and, on the other hand, indirectly as a result of increased renal absorption and thus retention of Na+ (rise in extracellular volume leads to hyperdynamic H.). The increased blood pressure leads to pressure diuresis with increased Na+ excretion, restoring Na+ balance (Guyton). This mechanism also exists in healthy people, but the pressure increase required for excretion of large amounts of NaCl is much lower. In primary H. (as in disorders of renal function) the NaCl-dependent increase in blood pressure is greater than normal. A diet that is low in Na+ can thus lower (not yet fixed) H. in these cases. A simultaneously elevated K+ supply accentuates this effect for unknown reasons. The cellular mechanism of salt sensitivity still awaits clarification. It is possible that changes in cellular Na+ transport are important. In fact cellular Na+ concentration is raised in primary H., which decreases the driving force for the 3 Na+/Ca2+ exchange carrier in the cell membrane, as a result of which the intracellular Ca2+concentration rises, which in turn increases the tone of the vasoconstrictor muscles (Blaustein). It is possible that digitalis like inhibitors of Na+-K+-ATPase are involved. They may be present in larger amounts, or there may be a special sensitivity to them in primary H. Atriopeptin (= atrial natriuretic peptide [ANP]), which has vasodilator and natriuretic effects, is probably not involved in the development of primary H. Although the concentration of renin is

not elevated in primary H., blood pressure can be reduced even in primary H. by inhibiting the angiotensin-converting enzyme (ACE inhibitors; see below) or angiotensin receptor antagonists. The various forms of secondary hypertension make up only 5 10% of all hypertensive cases, but contrary to primary H. their cause can usually be treated. Because of the late consequences of H., such treatment must be initiated as early as possible. Renal hypertension, the most common form of secondary H., can have the following, often partly overlapping, causes: Every renal ischemia, for example, resulting from aortic coarctation or renal artery stenosis, but also from narrowing of the renal arterioles and capillaries (glomerulonephritis, hypertension-induced atherosclerosis), leads to the release of renin in the kidneys. It splits the dekapeptide angiotensin I from angiotensinogen in plasma. A peptidase (angiotensinconverting enzyme, ACE), highly concentrated especially in the lungs, removes two aminoacids to form angiotensin II. This octapeptide has a strong vasoconstrictor action (TPR rises) and also releases aldosterone from the adrenal cortex (Na+ retention and increase in cardiac output), both these actions raising the blood pressure. In kidney disease with a significant reduction of the functioning renal mass, Na+ retention can therefore occur even during normal Na+ supply. The renal function curve is steeper than normal, so that Na+ balance is restored only at hypertensive blood pressure levels. Glomerulonephritis, renal failure, and nephropathy of pregnancy are some of the causes of the primarily hypervolemic form of renal H. Renal H. can also be caused by a renin-producing tumor or (for unknown reasons) by a polycystic kidney.

Ischemia of kidneys as a reason of secondary hypertension

The kidney is also central to other forms of hypertension that do not primarily originate from it (primary H., hyperaldosteronism, adrenogenital syndrome, Cushings syndrome). Furthermore, in every case of chronic H. secondary changes will occur sooner or later (vascular wall hypertrophy, atherosclerosis): they fix the H. even with effective treatment of the primary cause. If unilateral renal artery stenosis is repaired surgically rather late, for example, the other kidney, damaged in the meantime by the hypertension, will maintain the H.

Causes of Hypertension

Hormonal hypertension can have several causes:

In the adrenogenital syndrome cortisol formation in the adrenal cortex is blocked, and thus adrenocorticotropic hormone (ACTH) release is not inhibited. As a result excessive amounts of mineralocorticoid active precursors of cortisol and aldosterone, for example, 11-deoxycorticosterone (DOC), are produced and released. This leads to Na+retention, hence to an increase in extracellular volume (ECV) and thus to cardiac output H. Primary hyperaldosteronism (Conns syndrome). In this condition an adrenal cortical tumor releases large amounts of aldosterone without regulation. Also in this case Na+ retention in the kidney leads to cardiac output H. Cushings syndrome. Inadequate ACTH release (neurogenic cause; hypophyseal tumor) or an autonomous adrenal cortical tumor increase plasma glucocorticoid concentration, resulting ina raised catecholamine effect (cardiac output increased), and the mineralocorticoid action of high levels of cortisol (Na+ retention) lead to H. A similar effect occurs from eating large amounts of liquorice, because the glycyrrhizinic acid contained in it inhibits renal 11-hydroxysteroid dehydrogenase. As a result, cortisolin the kidneys is not metabolized to cortison but rather has its full effect on the renal mineralcorticoid receptor. Pheochromocytoma is an adrenomedullary tumor that produces catecholamines, resulting in uncontrolled high epinephrine and norepinephrine levels and thus both cardiac output hypertension and resistance hypertension. Contraceptive pills can cause Na+ retention and thus cardiac output hypertension.

Increased secretion of aldosterone as a reason of secondary hypertension

Neurogenic hypertension. Encephalitis, cerebral edemas or hemorrhage, and brain tumors may lead to a massive rise in blood pressure via central nervous stimulation of the sympathetic nervous system. An abnormally high central

stimulation of cardiac action as part of the hyperkinetic heart syndrome may also cause H. The consequences of hypertension most importantly result from atherosclerotic damage in arterial vessels, which can be observed well by means of fundoscopy. Because of the resulting increase in flow resistance, every form of hypertension ultimately creates a vicious circle. Vascular damage finally leads to ischemia of various organs and tissues (myocardium, brain, kidneys, mesenteric vessels, legs), renal ischemia accelerating the vicious circle. Damage to the vascular walls together with hypertension can, for example, lead to brain hemorrhage (stroke) and in the large arteries (e.g., aorta) to the formation of aneurysms and ultimately their rupture. Life expectancy is therefore markedly reduced. American life insurance companies, monitoring the fate of 1 million men whose blood pressure had been normal, slightly, or moderately elevated when aged 45 years, found that of those men who definitely had normal blood pressure (ca. 132/85 mm Hg) nearly 80% were still alive 20 years later, while of those with initially raised blood pressure (ca. 162/100 mm Hg) fewer than 50% had survived.

Consequences of Hypertension

MYOCARDIAL INFARCTION

Acute myocardial infarction (MI), also known as a heart attack, is characterized by the ischemic death of myocardial tissue associated with atherosclerotic disease of the coronary arteries. Risk factors. 1. Stress. Emotional or physical stress stimulates sympathetic link of the vegetative nervous system and hypothalamus-hypophysis-suprarenal system. Adrenalin stimulates -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 macroangiopathy). It results from hyperlipoproteinemia.

(so-called

Causes. If the myocardial ischemia lasts for some time (even at rest [unstable angina]), tissue necrosis, i.e., myocardial infarction (MI), occurs within about an hour. In 85 % of cases this is due to acute thrombus formation in the region of the atherosclerotic coronary stenosis. This development is promoted by turbulence, and atheroma rupture with collagen exposure. Both events activate thrombocytes (aggregation, adhesion, and vasoconstriction by release of thromboxan). Thrombosis is also encouraged through abnormal functions of the endothelium, thus its vasodilators (NO, prostacyclin) and antithrombotic substances are not present (tissue plasminogen activator [t-PA], antithrombin III, heparin sulfate, protein C, thrombomodulin, and prostacyclin). Rare causes of MI are inflammatory vascular diseases, embolism (endocarditis; valve prosthesis), severe coronary spasm (e.g., after taking cocaine), increased blood viscosity as well as a markedly raised O2 demand at rest (e.g., inaortic stenosis)

Acute Ischemia in Coronary Atherosclerosis

Atherosclerosis of Coronary Arteries

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.

Pathogenesis of Myocardial Infarction

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,KATPase 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 can not 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 -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 sustain normal 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 causes release of different myocardiocytes components that appear in the blood and are the diagnostic markers (myoglobin, creatine kinase, lactate dehydrogenase, 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 sustain normal 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 Infarction

ECG. A prominent characteristic of transmural infarction (tmI) is an abnormal Q wave of > 0.04 seconds and a voltage that is > 25 % of overall QRS voltage. It occurs within one day and is due to the necrotic myocardium not providing any electrical signal, so that when this myocardial segment should be depolarized

(within the first 0.04 s), the excitation vector of the opposite, normal portion of the heart dominates the summated vector. This 0.04 vector therefore points away from the site of infarction so that, for example, in anterior-wall infarction, it is registered particularly in leads V5, V6, I, and aVL as a large Q wave (and small R). (In a transmural infarction of the posterior wall such Q wave changes can not be registered with the conventional leads). Abnormal Q waves will still be present years later, i.e., they are not diagnostic of an acute infarction. An infarction that is not transmural usually causes no Q changes. ST segment elevation in the ECG is a sign of ischemic but not (yet) dead myocardial tissue. It occurs during an anginal attack (see above) in nontransmural infarction at the very beginning of transmural infarction at the margin of a transmural infarction that occurred hours to days before The ST segment returns to normal one to two days after an MI, but for the next few weeks the T wave will be inverted

ECG in Coronary Infarction

If sizeable portions of the myocardium die, enzymes are released from the myocardial cells into the bloodstream. It is not so much the level of enzyme concentrations as the temporal course of their maxima that is important in the

diagnosis of MI. Myocardial creatine kinase (CK-MB [MB=muscle, brain]) reaches its peak on day 1, aspartate aminotransferase (ASAT) on day 2, and myocardial lactate dehydrogenase (LDH1) on days three to five. Possible consequences of MI depend on site, extent, and scarring of the infarct. In addition to various arrhythmias, among them acutely life-threatening ventricular fibrillation, there is a risk of a number of morphological/mechanical complications: Tearing of the chordae tendineae resulting in acute mitral regurgitation; Perforation of the interventricular septum with left-to-right shunting; Fall in cardiac output that, together with stiffened parts of the ventricular wall (akinesia) due to scarring, will result in a high end-diastolic pressure. Still more harmful than a stiff infarct scar is a stretchable infarct area, because it will bulge outward during systole (dyskinesia), which will thereforeat comparably large scar areabe more likely to reduce cardiac output to dangerous levels (cardiogenic shock) than a stiff scar will; Finally, the ventricular wall at the site of the infarct can rupture to the outside so that acutely life-threatening pericardial tamponade occurs.

Consequences of MI

HEART FAILURE 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 cant pump into artery all blood, which comesby veins.

There are three pathophysiologic heart insufficiency variants:

1. 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.

2. Heart insufficiency because of myocardium damage. 3. 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).

4. 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.

Causes and Pathogenesis of Left Ventricular Failure

Stages of heart failure development Heart failure has three stages of development: the first emergency condition the second- stable adaptation (bouth these stages display the compensation) the third exhaustion (decompensation).

If the organism or some organs need more nutritious substances and O2 the heart work is increased in norm. 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). Compensatory mechanisms Compensatory mechanisms that are activated in heart failure include: increased ventricular preload, or the Frank-Starling mechanism, by ventricular dilatation and volume expansion; peripheral vasoconstriction, which initially maintains perfusion to vital organs; myocardial hypertrophy to preserve wall stress as the heart dilates; renal sodium and water retention to enhance ventricular preload; and initiation of the adrenergic nervous system, which raises heart rate and contractile function. These processes are controlled mainly by activation of various neurohormonal vasoconstrictor systems, including RAAS, the adrenergic nervous system, and non-osmotic release of arginine-vasopressin. These and other mechanisms contribute to the symptoms, signs, and poor natural history of heart failure. In particular, an increase in wall stress along with neurohormonal activation facilitates pathological ventricular remodelling; this process has been closely linked to heart failure disease progression. Management of chronic heart failure targets these mechanisms and, in some instances, results in reverse remodelling of the failing heart. 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 cardiomyocite functional units loading, therefore muscular and connective cells genes are activated. Consequently, in experimental animal over a little hours after constriction of aorta in heart cells appear the reinforcing signs of nuclear function, RNA synthesis augmentations and amount of ribosomes. This indicates on that albumens synthesis in myocardium cells mainly regulates by loading level. Also this process is controled by mechanisms of nevro-humoral regulation. Myocardium hypertrophy - adaptive phenomenon, directed on execution of raised work without essential loading rise of myocardium units mass. This is perfect adaptation. Consequently, sportsmens myocardium hypertrophy allows heart to execute great work. Nervous heart regulation also changes, that considerably broadens a diapason of itsadaptation and possibility to be tolerance to long time loadings. But also at the pathological processes in the heart hypertrophy can compensate the long timeviolations. An hypertrophic 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, that is attended with change of intracellularstructures correlation.

Myocardium hypertrophy

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 plays 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 fibrealso 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 than nuclear 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 violation and 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 have 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 structures 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 contents of norepinephrine inmyocardium 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 measuresof 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 cardiacmuscles causes of functions. The main reason is contractive function disorder in the result of insufficient energy synthesis by mitochondrias and also violation of energy using bycontractive fibres.

One of these pathological variants can prevail at different heart insufficiency types, for example, violation of using energy is main in case of long time heart hyperfunction. At the same time can appear contractive function depression common aggravation of muscle fibre 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 andsubstitute 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 whenreplacement by connecting tissue 20-0 % of heart mass is really. Dilatation of heart cavities can arises at distrophy of myocardium, it causes further decrease of cardiaccontraction 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 (Beinbriges 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, whichprovides 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 ofcreatinphosphate, intracellular potassium concentration decrease and sodium one increase, stimulation of glycolysis and lactate accumulation). This stage is characterized by thefast 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 couldnt 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 powercreating and contractiveelements 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. Chronic heart insufficiency

Chronic 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 time 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 contractivemyocardium 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 rteriole. But then a less stronger right ventricle is overloaden, that leads to its decompensation and development of the rightventricle 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 results 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, 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 a cardiomyocites 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 ofoxidative metabolism violation cardiomyocyte or antioxidant systems insufficiency. First functions of specific membrane pumps (Na+, +-P-ase, ++-P-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 - and 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. The number of working cardiomyocytes decreases and it leads to their overload, thus mechanisms of compensations are the same as earlier prescribed.

Heart Failure: Pathogenesis of Syndroms

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).