Coronary artery disease is considered the primary cause of disability and death, and leads to many chronic diseases. Its appearance is due to insufficient blood flow, which leads to starvation of the organ, and also does not allow the supply of oxygen to other tissues to the full.
Most often, the development of ischemia is provoked by atherosclerosis of the coronary arteries, when, due to cholesterol plaques, the lumen in them narrows, reducing blood flow. In the second place of the appearance of the disease are thrombosis, spasm, arterial embolism, then congenital pathologies.
Anatomy
To supply the body with oxygen and nutrients at all times, the heart must receive enough energy to pump blood. Every minute a muscle organ requires much more oxygen for its work than others.
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The intensive regimen requires uninterrupted operation of the right and left coronary arteries, which, due to their functional characteristics, are capable of doing this. The anterior interventricular and circumflex are the branches into which the left artery is divided.
To supply the left and partially right ventricles, blood flows through the anterior interventricular branch. The branching of the vessels that extend from it feed the interventricular septum by 2/3.
The left atrium, the anterior and posterior walls of the left ventricle, and the sinus section are supplied with blood due to the circumflex branch of the left coronary artery.
Other parts of the organ are supplied with blood by the right artery. Due to individual differences due to the location of the arteries, myocardial blood flow can be carried out in different ways.
Therefore, the blood supply to the heart can be:
- uniform;
- left-handed;
- right-winged.
When uniform, both arteries perform their work equally, the blood supply is stable and without deviations. This type of blood supply is considered the most common. The other two types are due to the dominance of one of the large vessels.
The functional significance of the left coronary artery predominates over the right one; it most often provides most of the organ with blood. The blood supply to the heart muscle is provided by a branched network of sinuses, capillaries, vessels; blood outflow occurs through the veins.
Anatomically, the coronary arteries originate from the orifice of the aorta, due to which they are dominated by increased pressure, which promotes blood flow. Even when a person is in a calm state, the heart is able to extract up to 75% of oxygen from the blood, which becomes energy for him, enabling him to work.
In pathology, an important role for coronary supply is assigned to the formation of intercoronary anastomoses, the number of which exceeds 10–20% of the normal course of processes. Their formation, quantity and size are influenced not by the age of a person, but by the presence of coronary atherosclerosis or valvular disease.
Norms
To provide coronary blood flow that will meet the needs of the heart muscle, good arterial capacity is required. In a healthy person, the level of blood flow can increase by 5-6 times with intense exercise compared with a calm state.
When the load on the heart increases, blood flow in the coronary arteries increases due to:
- the pressure that is created in them;
- due to the expansion of the coronary arteries, which reduces the resistance to blood flow;
- increased heart rate.
The development of myocardial pathology and the occurrence of ischemic heart disease in any healthy person is influenced by the presence of reasons that can cause it, but also by the anatomical structure - vascular and arterial tortuosity, high pressure that is created in them.
In comparison with other parts of the cardiovascular system, the occurrence of atherosclerosis is observed here most often.
With ischemia, only a small percentage of people do not experience changes in the coronary arteries; most people have their atherosclerosis.
Fundamentals of the pathogenesis of ischemic heart disease
Ischemia of the heart muscle causes a number of events:
- decrease in pressure in the coronary arteries;
- metabolism without the use of oxygen (anaerobic metabolism);
- mechanical changes in the myocardium, when its diastolic function and contractility are disturbed;
- changes in the electrocardiogram;
- pain manifestations.
When blood flow is restored and ischemia disappears, postischemic depression of metabolic processes and functions of the heart muscle is observed for a long time, up to several days.
The ischemic cascade ends with clinical manifestations precisely at subsequent stages, which can lead to ventricular fibrillation. The functional state of the myocardium is not able to quickly recover, metabolic disorders do not disappear, even if the pain syndrome is stopped.
The pathogenesis of ischemic heart disease is significantly influenced by the number of arteries affected by atherosclerosis and the degree of narrowing of the lumens in them. Important factors that affect the course of the disease are:
| Atherosclerotic plaques | The location of the plaques in the vessels is also important. Most of the dying people have a 75% degree of damage to the main arteries. Most often, atherosclerosis affects:
The most dangerous for health is the localization of plaques in the trunk of the left artery, which leads to severe angina pectoris and sudden death. But intense loads are also significant in the case of damage to small vessels extending from the coronary arteries. The development of soft atherosclerotic plaques with a thin lining, which do not cause significant vasoconstriction, leads to their rapid growth and rupture due to structural features. Blood enters the formed microcracks, increasing the size of the plaque. Its contents are thrown out along with the bloodstream into the artery, which rather leads to thrombosis, stenoses the artery, provoking angina pectoris, heart attack, and sudden death. But events may unfold in a different way. The coating of the plaque becomes denser, its volume decreases, which increases blood flow. At the same time, the likelihood of the occurrence of pathology decreases. IHD can be characterized as a monotonous process in which exacerbation phases are replaced by stabilization. |
| Vascular spasms |
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| Blood clots |
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Three main factors, depending on the individual characteristics of a person and the stage of the course of the disease, can cause the progression of IHD, and can lead to tolerable chronic pathology. But the process of plaque formation is basic and most important.
Clinical forms
The diagnosis of ischemic heart disease is established using its clinical form, adopted according to the WHO classification. In most patients, the disease occurs suddenly, without a previous clinic, in a smaller number of people, the development occurs gradually, when the symptoms increase over time.
Clinical manifestations suggest that the patient has:
| Sudden coronary death |
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| Angina pectoris |
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| Myocardial infarction |
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|
|
| Heart rhythm disorders | Arrhythmia can occur against the background of various diseases, sometimes not associated with the functions of the heart, but most often it accompanies atherosclerotic pathology. |
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Ischemia occurs due to lack of oxygen due to inadequate perfusion. The etiology of coronary heart disease is very diverse. Common to various forms of coronary heart disease is a disruption in the work of the heart muscle due to a mismatch between the supply of oxygen to the myocardium and the need for it.
Ischemic Heart Disease (IHD): Etiology and Pathophysiology
The most common cause of myocardial ischemia is atherosclerotic changes in the epicardial coronary arteries, which lead to narrowing of these arteries, which leads to a decrease in myocardial perfusion at rest or limiting the possibility of an adequate increase in myocardial perfusion when there is a need for its increase. Coronary blood flow also decreases in the presence of blood clots in the coronary arteries, when a spasm occurs in them, sometimes - when the coronary arteries are embolized, narrowed by syphilitic gums. Congenital coronary artery anomalies, such as abnormal separation of the left anterior descending coronary artery from the pulmonary trunk, can cause myocardial ischemia and even infarction in children, but they rarely cause myocardial ischemia in adults. Myocardial ischemia can also occur with a significant increase in myocardial oxygen demand, as, for example, with severe left ventricular hypertrophy due to hypertension or stenosis of the aortic opening. In the latter case, angina attacks may occur, which cannot be distinguished from angina attacks that occur with atherosclerosis of the coronary arteries. Rarely, myocardial ischemia can occur when the blood's ability to carry oxygen is reduced, for example, when anemia is unusually severe or when carboxyhemoglobin is present in the blood. Often, myocardial ischemia can be caused by two or more reasons, for example, an increase in oxygen demand due to left ventricular hypertrophy and a decrease in myocardial oxygen supply due to atherosclerosis of the coronary arteries.
Normally, coronary circulation is regulated and controlled by myocardial oxygen demand. This occurs as a result of significantly changing coronary resistance and hence blood flow. At the same time, the amount of oxygen extracted by the myocardium from the blood is relatively constant and large enough. Normally, intramyocardial resistive arteries have a very significant ability to expand. The change in oxygen demand that occurs during physical and emotional stress affects coronary resistance and thus regulates the supply of blood and oxygen (metabolic regulation). The same vessels adapt to physiological changes in blood pressure and thereby maintain coronary blood flow at a level corresponding to the needs of the myocardium (autoregulation). The large epicardial coronary arteries, although capable of narrowing and dilating, in healthy individuals serve as a reservoir and are considered only as conducting vessels. At the same time, the intramyocardial arteries normally can significantly change their tone and therefore are considered as resistive vessels.
Coronary atherosclerosis. Atherosclerotic changes are localized mainly in the epicardial coronary arteries. Subintimal deposits of pathological fats, cells and decay products, i.e., atherosclerotic plaques, are distributed unevenly in different segments of the epicardial coronary network. An increase in the size of these plaques leads to a narrowing of the vessel lumen. There is a relationship between pulsating blood flow and the size of the stenosis. Experimental studies have shown that when the degree of stenosis reaches 75% of the total area of the vessel lumen, the maximum increase in blood flow in response to the increasing myocardial oxygen demand is no longer possible. If the degree of stenosis is more than 80%, then a decrease in blood flow is possible at rest. A further, even very small increase in the degree of stenosis leads to a significant restriction of coronary blood flow and the appearance of myocardial ischemia.
Segmental atherosclerotic narrowing of the epicardial coronary arteries is more often caused by the formed plaques, in the area of which cracks, hemorrhages, and blood clots can occur. Any of these complications can lead to a temporary increase in the degree of obstruction and a decrease in coronary blood flow and cause clinical manifestations of myocardial ischemia. The area of ischemic myocardium and the severity of clinical manifestations depend on the localization of the stenosis. The narrowing of the coronary artery, which is the cause of myocardial ischemia, often contributes to the development of collateral vessels, especially in cases where this narrowing develops gradually. If the collateral vessels are well developed, they can provide sufficient blood flow to maintain normal myocardial function at rest, but not with increased myocardial oxygen demand.
As soon as the severity of stenosis of the proximal part of the epicardial artery reaches 70% or more, distally located resistive vessels dilate, their resistance decreases, and thereby maintenance of adequate coronary blood flow is ensured. This leads to the appearance of a pressure gradient in the area of proximal stenosis: post-stenotic pressure drops, with maximum expansion of resistive vessels, myocardial blood flow becomes dependent on pressure in that part of the coronary artery, which is located distal to the site of obstruction. After the resistive vessels have expanded as much as possible, disturbances in myocardial oxygen supply can be caused by changes in myocardial oxygen demand, as well as a change in the caliber of the stenotic coronary artery due to physiological fluctuations in its tone, pathological spasm of the coronary artery, and the formation of small platelet plugs. All this can adversely affect the relationship between oxygen delivery to the myocardium and the myocardial demand for it and cause the appearance of myocardial ischemia.
Consequences of ischemia. Inadequate oxygen supply to the heart muscle caused by coronary atherosclerosis can lead to disruption of the mechanical, biochemical and electrical functions of the myocardium. The sudden development of ischemia usually affects the function of the left ventricular myocardium, which leads to a violation of the processes of relaxation and contraction. Due to the fact that the subendocardial parts of the myocardium are poorly supplied with blood, ischemia of these areas develops in the first place. Ischemia, involving large segments of the left ventricle, leads to the development of transient insufficiency of the latter. If ischemia also affects the area of the papillary muscles, then it can be complicated by the insufficiency of the left atrioventricular valve. If ischemia is transient, it is manifested by the occurrence of an attack of angina pectoris. With prolonged ischemia, myocardial necrosis may occur, which may or may not be accompanied by the clinical picture of acute myocardial infarction. Coronary atherosclerosis is a local process that can cause ischemia of varying degrees. Focal impairments of left ventricular contractility resulting from ischemia cause segmental bulging or dyskinesia and can significantly reduce the pumping function of the myocardium.
The aforementioned mechanical disorders are based on a wide range of changes in cell metabolism, their function and structure. In the presence of oxygen, the normal myocardium metabolizes fatty acids and glucose into carbon dioxide and water. In conditions of oxygen deficiency, fatty acids cannot be oxidized, and glucose is converted into lactate; The pH inside the cell decreases. In the myocardium, the reserves of high-energy phosphates, adenosine triphosphate (ATP) and creatine phosphate decrease. Dysfunction of cell membranes leads to a lack of K ions and the absorption of Na ions by myocytes. Whether these changes are reversible or they lead to the development of myocardial necrosis depends on the degree and duration of the imbalance between the supply of oxygen to the myocardium and the need for it.
With ischemia, the electrical properties of the heart are also impaired. The most characteristic early electrocardiographic changes are repolarization disorders, which are T wave inversion, and later - ST segment displacement. Transient ST-segment depression often reflects subendocardial ischemia, while transient ST-segment elevation is thought to be a consequence of more severe transmural ischemia. In addition, due to myocardial ischemia, its electrical instability occurs, which can lead to the development of ventricular tachycardia or ventricular fibrillation.
In most cases, the sudden death of patients with coronary heart disease is explained precisely by the occurrence of severe rhythm disturbances due to myocardial ischemia.
Coronary artery disease (CAD): Clinical manifestations of ischemia
Asymptomatic course of coronary heart disease and its course, accompanied by clinical manifestations.
Posthumous studies of victims of accidents and those killed in wartime have shown that atherosclerotic changes in the coronary arteries usually occur before the age of 20. These changes occur in adults who did not have clinical manifestations of the disease during their lifetime. With the help of an exercise test in persons without clinical manifestations of coronary heart disease, it is sometimes possible to identify the so-called "silent" myocardial ischemia, ie, the presence of ECG changes characteristic of myocardial ischemia, not accompanied by an attack of angina pectoris. In such patients, coronary angiography often reveals obstructive changes in the coronary arteries. Postmortem examinations of individuals with obstructive changes in the coronary arteries who did not show signs of myocardial ischemia during life often reveal macroscopic scarring, which is evidence of myocardial infarction, in the areas of blood supply to the affected coronary artery. In addition, population studies have shown that approximately 25% of patients with acute myocardial infarction are ignored by doctors due to the atypical clinical picture of the disease. The prognosis of life in such patients and the likelihood of complications in them are the same as in patients with a classical clinical picture. Sudden death is always unexpected and is usually the result of coronary heart disease. In patients who do not have clinical manifestations of ischemia before the development of heart failure, the first manifestations of coronary heart disease may be cardiomegaly or heart failure, which developed as a result of ischemic damage to the left ventricular myocardium. This condition is classified as ischemic cardiomyopathy. In contrast to the asymptomatic course of coronary heart disease, the clinically expressed form of the disease is manifested by chest pain due to angina pectoris or myocardial infarction. After the first appearance of clinical signs, the disease can proceed stably, or progress, or again take an asymptomatic form, or end in sudden death.Ischemic heart disease (IHD) is a disease that develops when there is insufficient oxygen supply to the heart muscle through the coronary arteries. The most common cause of this is atherosclerosis of the coronary arteries with plaque formation and narrowing of their lumen. It can be acute and chronic (long-term). The manifestations of ischemic heart disease can be: angina pectoris, myocardial infarction, cardiac arrhythmias, as well as sudden cardiac death.
Prevalence
In developed countries, coronary heart disease has become the most common cause of death and disability, accounting for about 30 percent of deaths. It is far ahead of other diseases as a cause of sudden death and occurs in one in three women and half of men. This difference is due to the fact that female sex hormones are one of the means of protection against atherosclerotic vascular lesions. Due to the change in hormonal levels during menopause, the likelihood of a heart attack in women after menopause increases significantly.
Forms
Depending on how pronounced the oxygen deprivation of the heart, how long it lasts, and how quickly it arose, several forms of coronary heart disease are distinguished.
- Asymptomatic, or "mute" form of ischemic heart disease- does not cause complaints from the patient.
- Exertional angina- a chronic form, manifested by shortness of breath and pain behind the sternum during physical exertion and stress, with the action of some other factors.
- Unstable angina- any attack of angina pectoris, markedly superior in strength to the previous ones or accompanied by new symptoms. Such intensifying attacks indicate a worsening of the course of the disease and can be harbingers of myocardial infarction.
- Arrhythmic form- is manifested by cardiac arrhythmias, most often atrial fibrillation. It occurs acutely and can become chronic.
- Myocardial infarction- an acute form, the death of a portion of the heart muscle, caused most often by the detachment of a plaque from the wall of the coronary artery or a thrombus and a complete blockage of its lumen.
- Sudden cardiac death- cardiac arrest, in most cases, caused by a sharp decrease in the amount of blood supplied to it as a result of complete blockage of a large artery.
These shapes can be combined and superimposed on one another. For example, arrhythmia is often associated with angina pectoris, and then a heart attack occurs.
Causes and mechanism of development
Despite the fact that the heart pumps blood in the body, it itself needs a blood supply. The heart muscle (myocardium) receives blood through two arteries that extend from the root of the aorta and are called coronary(due to the fact that they go around the heart like a crown). Further, these arteries are divided into several smaller branches, each of which feeds its own part of the heart.
There are no more arteries that bring blood to the heart. Therefore, with a narrowing of the lumen or blockage of one of them, the area of the heart muscle lacks oxygen and nutrients, and the disease develops.
The main cause of coronary artery disease is currently considered atherosclerosis of the coronary arteries with the deposition of cholesterol plaques in them and narrowing of the lumen of the artery (coronary disease). As a result, blood cannot flow to the heart in sufficient volume.
At first, the lack of oxygen manifests itself only during increased stress, for example, when running or walking fast with a load. The pains behind the breastbone that appear at the same time are called exertional angina. As the lumen of the coronary arteries narrows and the metabolism of the heart muscle worsens, pain begins to appear at an ever lower load, and eventually at rest.
Simultaneously with angina pectoris, chronic heart failure may develop, manifested by edema and shortness of breath.
With a sudden rupture of the plaque, complete occlusion of the arterial lumen, myocardial infarction, cardiac arrest, and death can occur. The degree of damage to the heart muscle in this case depends on in which artery or branch the blockage occurred - the larger the artery, the worse the consequences.
In order for myocardial infarction to develop, the lumen of the artery must decrease by at least 75%. The slower and more gradual this happens, the easier it is for the heart to adapt. A severe blockage is most dangerous and often fatal.
Symptoms
Depending on the form of the disease:
- Asymptomatic form- there are no manifestations of the disease, it is detected only during examination.
- Exertional angina- pain behind the sternum of a pressing nature (as if a brick was laid), given to the left arm, neck. Shortness of breath when walking, climbing stairs.
- Arrhythmic form- shortness of breath, palpitations, interruptions in the work of the heart.
- Myocardial infarction- severe pain behind the breastbone, reminiscent of an attack of angina pectoris, but more intense and not relieved by conventional means.
Course and prognosis
The course of coronary heart disease is irreversible. This means that there are no remedies to completely cure it. All modern methods of treatment allow one or another to control the course of the disease and slow down its development, but they cannot reverse the process.
The defeat of the heart goes on continuously and in parallel with other organs: kidneys, brain, pancreas. This process is called the "cardiovascular continuum" and includes diseases such as coronary artery disease, atherosclerosis, hypertension, stroke, atrial fibrillation, metabolic syndrome and others. All these diseases are interrelated and due to common causes.
Briefly, the main stages of the cardiovascular continuum can be described as follows.
- Asymptomatic stage- risk factors have a negative effect, cholesterol deposits appear in the vessels of the heart, but their lumen is still wide enough.
- The appearance of the first harbingers- high blood pressure, blood sugar, cholesterol. At this stage, cholesterol plaques in the vessels grow and can already close up to 50% of the lumen. In the heart muscle, remodeling processes begin, that is, changes in its structure, which lead to heart failure.
- The onset and increase of symptoms- shortness of breath, interruptions in the work of the heart, chest pain. On ultrasound of the heart, by this time, the expansion of the cavities of the heart, thinning of the heart muscle, becomes visible. The lumen of the arteries is even more narrowed.
- Final stage- the appearance of congestive heart failure, a sharp deterioration in the work of the heart, the appearance of edema, congestion in the lungs, a sharp increase in pressure, atrial fibrillation. Pain behind the sternum at the slightest exertion and even at rest.
At any of these stages, but usually in the third or fourth stage, myocardial infarction or sudden cardiac arrest may occur. A heart attack does not necessarily lead to death, but after it ischemic disease always accelerates its course.
Good day, dear readers!
In today's article we will consider with you such a disease as ischemic heart disease (IHD), as well as its symptoms, causes, classification, diagnosis, treatment, folk remedies and prevention of ischemic heart disease. So…
What is coronary artery disease?
Coronary artery disease (CHD)- a pathological condition characterized by insufficient blood supply and, accordingly, oxygen to the heart muscle (myocardium).
Synonyms for ischemic heart disease- Coronary heart disease (CHD).
The main and most common cause of coronary artery disease is the appearance and development of atherosclerotic plaques in the coronary arteries, which narrow and sometimes block blood vessels, thereby disrupting the normal blood flow in them.
Now let's move on to the development of the ischemic heart disease itself.
The heart, as we all know, is a human "motor", one of the main functions of which is to pump blood throughout the body. However, like a car engine, without enough fuel, the heart stops functioning normally and can stop.
The function of fuel in the human body is performed by blood. Blood delivers oxygen, nutrients and other substances necessary for normal functioning and life to all organs and parts of the body of a living organism.
The blood supply to the myocardium (heart muscle) occurs via 2 coronary vessels that branch off from the aorta. The coronary vessels, which are divided into a large number of small vessels, bend around the entire heart muscle, feeding each part of it.
If there is a decrease in the lumen or blockage of one of the branches of the coronary vessels, that part of the heart muscle remains without food and oxygen, the development of coronary heart disease begins, or as it is also called, coronary heart disease (CHD). The larger the artery is blocked, the worse the consequences of the disease.
The onset of the disease usually manifests itself in the form of strong physical exertion (running and others), but over time, if no action is taken, pain and other signs of coronary artery disease begin to haunt the person even during rest. Some signs of coronary artery disease are also - shortness of breath, swelling, dizziness.
Of course, the above model of the development of coronary heart disease is very superficial, but it reflects the very essence of the pathology.
IHD - ICD
ICD-10: I20-I25;
ICD-9: 410-414.
The first signs of ischemic heart disease are:
- Increased blood sugar;
- High cholesterol levels;
The main signs of ischemic heart disease, depending on the form of the disease, are:
- Exertional angina- characterized by pressing pain behind the sternum (capable of giving to the left side of the neck, left shoulder blade or arm), shortness of breath during physical exertion (brisk walking, running, climbing stairs) or emotional stress (stress), increased blood pressure;
- Arrhythmic form- accompanied by shortness of breath, cardiac asthma, pulmonary edema;
- - a person develops an attack of severe pain behind the breastbone, which cannot be relieved by conventional pain medications;
- Asymptomatic form- the person has no obvious signs indicating the development of coronary artery disease.
- , malaise;
- Swelling, mostly
- , clouding of consciousness;
- sometimes with seizures;
- Heavy sweating;
- Feelings of fear, anxiety, panic;
- If nitroglycerin is taken during painful attacks, the pain subsides.
The main and most frequent reason for the development of ischemic heart disease is, the mechanism of which we spoke about at the beginning of the article, in the paragraph "Development of ischemic heart disease". In short, the essence lies in the presence of atherosclerotic plaques in the coronary blood vessels, narrowing or completely blocking the access of blood to one or another part of the heart muscle (myocardium).
Other causes of coronary artery disease include:
- Eating - fast foods, soft drinks, alcoholic beverages, etc.;
- Hyperlipidemia (increased levels of lipids and lipoproteins in the blood);
- Thrombosis and thromboembolism of the coronary arteries;
- Spasms of the coronary arteries;
- Dysfunction of the endothelium (the inner wall of blood vessels);
- Increased activity of the blood coagulation system;
- Damage to blood vessels - herpes virus, chlamydia;
- Hormonal imbalance (with the onset of menopause, and other conditions);
- Metabolic disorders;
- Hereditary factor.
The following people are at increased risk of developing coronary artery disease:
- Age - the older the person, the higher the risk of developing coronary artery disease;
- Bad habits - smoking, drugs;
- Poor quality food;
- Sedentary lifestyle;
- Frequent exposure;
- Male;
IHD classification
The classification of coronary artery disease occurs in the form:
1. :
- Exertional angina pectoris:
- - Primary;
- - Stable, indicating the functional class
- Unstable angina (Braunwald classification)
- Vasospastic angina;
2. Arrhythmic form (characterized by a violation of the heart rhythm);
3. Myocardial infarction;
4. Postinfarction;
5. Heart failure;
6. Sudden coronary death (primary cardiac arrest):
- Sudden coronary death with successful resuscitation;
- Sudden coronary death with a fatal outcome;
7. Asymptomatic form of ischemic heart disease.
Diagnosis of ischemic heart disease
Diagnosis of coronary heart disease is carried out using the following examination methods:
- Anamnesis;
- Physical research;
- Echocardiography (EchoECG);
- Angiography and CT angiography of the coronary arteries;
How is coronary heart disease treated? Treatment of ischemic heart disease is carried out only after a thorough diagnosis of the disease and determination of its form, because the method of therapy and the means necessary for it depend on the form of ischemic heart disease.
Treatment for coronary artery disease usually includes the following therapies:
1. Restriction of physical activity;
2. Drug treatment:
2.1. Anti-atherosclerotic therapy;
2.2. Supportive therapy;
3. Diet;
4. Surgical treatment.
1. Restriction of physical activity
As we already know, dear readers, the main point of ischemic heart disease is insufficient blood supply to the heart. In connection with an insufficient amount of blood, of course, the heart does not receive enough oxygen, along with various substances necessary for its normal functioning and life. At the same time, you need to understand that with physical exertion on the body, the load on the heart muscle increases in parallel, which at one time wants to receive an additional portion of blood and oxygen. Naturally, since with coronary artery disease, blood is already insufficient, then under load this insufficiency becomes even more critical, which contributes to a worsening of the course of the disease in the form of intensified symptoms, up to a sharp cardiac arrest.
Physical activity is necessary, but already at the stage of rehabilitation after the acute stage of the disease, and only as directed by the attending physician.
2. Drug treatment (drugs for coronary artery disease)
Important! Before using medications, be sure to consult with your doctor!
2.1. Anti-atherosclerotic therapy
Recently, for the treatment of ischemic heart disease, many doctors have been using the following 3 groups of drugs - antiplatelet agents, β-blockers and cholesterol-lowering (cholesterol-lowering) drugs:
Antiplatelet agents. By preventing the aggregation of erythrocytes and platelets, antiplatelet agents minimize their adhesion and settling on the inner walls of blood vessels (endothelium), improve blood flow.
Among antiplatelet agents, the following drugs can be distinguished: acetylsalicylic acid ("Aspirin", "Acecardol", "Thrombol"), "Clopidogrel".
β-blockers. Beta-blockers help to lower the heart rate (HR), thereby reducing the load on the heart. In addition, with a decrease in heart rate, oxygen consumption also decreases, due to the lack of which ischemic heart disease mainly develops. Doctors note that with the regular use of β-blockers, the quality and life expectancy of the patient improves, because this group of drugs relieves many symptoms of coronary artery disease. However, you should be aware that contraindications to the use of β-blockers are the presence of such concomitant diseases as -, pulmonary pathologies and chronic obstructive pulmonary disease (COPD).
Among the β-blockers, the following drugs can be distinguished: bisoprolol (Biprol, Cordinorm, Niperten), carvedilol (Dilatrend, Coriol, (Talliton), metoprolol (Betalok, Vasokardin, Metocard "," Egilok ").
Statins and fibrates- cholesterol-lowering (cholesterol-lowering) drugs. These groups of drugs lower the amount of "bad" cholesterol in the blood, reduce the number of atherosclerotic plaques on the walls of blood vessels, and also prevent the appearance of new plaques. The combined use of statins and fibrates is the most effective way to combat cholesterol deposits.
Fibrates increase the amount of high density lipoproteins (HDL), which actually counteract low density lipoproteins (LDL), and as we all know, it is LDL that forms atherosclerotic plaques. In addition, fibrates are used in the treatment of dyslipidemia (IIa, IIb, III, IV, V), lowering triglyceride levels and, most importantly, minimizing the percentage of deaths from coronary artery disease.
Among the fibrates, the following drugs can be distinguished - "Fenofibrate".
Statins, in contrast to fibrates, have a direct effect on LDL, lowering its amount in the blood.
Among statins, the following drugs can be distinguished - "Atorvastin", "Lovastatin", "Rosuvastin", "Simvastatin".
The level of cholesterol in the blood in IHD should be - 2.5 mmol / l.
2.2. Supportive therapy
Nitrates. They are used to reduce the preload on the work of the heart by expanding the blood vessels of the venous bed and depositing blood, thereby stopping one of the main symptoms of coronary heart disease - angina pectoris, manifested in the form of shortness of breath, heaviness and pressing pain behind the sternum. Especially for the relief of severe attacks of angina pectoris, intravenous drip of nitroglycerin has recently been successfully used.
Among the nitrates, the following drugs can be distinguished: "Nitroglycerin", "Isosorbide mononitrate".
Contraindications to the use of nitrates are below 100/60 mm Hg. Art. Of the side effects, a decrease in blood pressure can also be noted.
Anticoagulants. They prevent the formation of blood clots, slow down the development of existing blood clots, inhibit the formation of fibrin filaments.
Among anticoagulants, the following drugs can be distinguished: "Heparin".
Diuretics (diuretics). Promote the accelerated elimination of excess fluid from the body, due to a decrease in the volume of circulating blood, thereby reducing the load on the heart muscle. Among the diuretics, 2 groups of drugs can be distinguished - loop and thiazide.
Loop diuretics are used in emergency situations when fluid from the body needs to be removed as quickly as possible. A group of loop diuretics reduce the reabsorption of Na +, K +, Cl- in the thick part of Henle's loop.
Among loop diuretics, the following drugs can be distinguished - "Furosemide".
Thiazide diuretics reduce the reabsorption of Na +, Cl- in the thick part of the loop of Henle and the initial section of the distal tubule of the nephron, as well as the reabsorption of urine, and retain it in the body. Thiazide diuretics, in the presence of hypertension, minimize the development of coronary heart disease complications from the cardiovascular system.
Among thiazide diuretics, the following drugs can be distinguished - "Hypothiazide", "Indapamide".
Antiarrhythmic drugs. They contribute to the normalization of the heart rate (HR), thereby improving the respiratory function, facilitating the course of ischemic heart disease.
Among antiarrhythmic drugs, the following drugs can be distinguished: "Aimalin", "Amiodarone", "Lidocaine", "Novocainamide".
Angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors, by blocking the conversion of angiotensin II from angiotensin I, prevent blood vessel spasms. ACE inhibitors also normalize, protect the heart and kidneys from pathological processes.
Among the ACE inhibitors, the following drugs can be distinguished: "Captopril", "Lisinopril", "Enalapril".
Sedatives. They are used as a means of calming the nervous system when the cause of an increase in the heart rate is emotional experiences, stress.
Among the sedatives are: "Valerian", "Persen", "Tenoten".
The diet for ischemic heart disease is aimed at reducing the load on the heart muscle (myocardium). To do this, limit the amount of water and salt in the diet. Also, products that contribute to the development of atherosclerosis are excluded from the daily diet, which can be found in the article -.
Of the main points of the diet for ischemic heart disease, one can single out:
- Calorie content of food - by 10-15%, and with obesity by 20% less than your daily diet;
- The amount of fat - no more than 60-80 g / day;
- The amount of proteins - no more than 1.5 g per 1 kg of human body weight / day;
- The amount of carbohydrates - no more than 350-400 g / day;
- The amount of table salt is no more than 8 g / day.
What not to eat with coronary artery disease
- Fatty, fried, smoked, spicy and salty foods - sausages, sausages, ham, fatty dairy products, mayonnaises, sauces, ketchups, etc.;
- Animal fats, which are found in large quantities in lard, fatty meats (pork, domestic duck, goose, carp and others), butter, margarine;
- High-calorie foods, as well as foods rich in easily digestible carbohydrates - chocolate, cakes, pastry, sweets, marshmallows, marmalade, preserves and jams.
What can you eat with ischemic heart disease
- Food of animal origin - lean meats (lean chicken, turkey, fish), low-fat cottage cheese, egg white;
- Groats - buckwheat, oatmeal;
- Vegetables and fruits - predominantly green vegetables and orange fruits;
- Bakery products - rye or bran bread;
- Drinking - mineral waters, low-fat milk or kefir, unsweetened tea, and juices.
In addition, the diet for ischemic heart disease should be aimed at eliminating an excessive amount of extra pounds (), if present.
For the treatment of coronary heart disease, M.I. Pevzner developed a therapeutic food system - diet No. 10c (table No. 10c). These vitamins, especially C and P, strengthen the walls of blood vessels and prevent cholesterol deposits in them, i.e. the formation of atherosclerotic plaques.
Ascorbic acid also promotes the rapid breakdown of "bad" cholesterol and its excretion from the body.
Horseradish, carrots and honey. Grate the horseradish root to make 2 tbsp. spoons and fill it with a glass of boiled water. After, mix the horseradish infusion with 1 cup of freshly squeezed carrot juice and 1 cup of honey, mix everything thoroughly. You need to drink the product in 1 tbsp. spoon, 3 times a day, 60 minutes before meals.
18849 0
IHD is a discrepancy between coronary blood flow and metabolic needs of the myocardium, i.e. the volume of oxygen consumption by the myocardium (PMO 2). (Fig. 1).
Rice. 1. Diagram of the balance of supplied and consumed energy and the factors that determine their levels
The equivalent of the efficiency of the heart as a pump is the PMO level 2, the delivery of which is provided by the coronary blood flow (Qcor). The amount of coronary blood flow is regulated by the tonic state of the coronary vessels and the pressure difference in the ascending aorta and the left ventricular cavity, which corresponds to the intramyocardial pressure (tension):
P 1 - pressure in the ascending aorta,
Р 2 - pressure in the left ventricle (intramyocardial tension),
R cor is the resistance of the coronary vessels.
The energy supply of the pumping function of the heart in a wide range of its activity - from the state of rest to the level of maximum load, occurs due to the coronary reserve. Coronary reserve - the ability of the coronary vascular bed to increase the coronary blood flow many times in proportion to the PMO 2 level, due to the dilatation of the coronary vessels. (Fig. 2).
The magnitude of the coronary reserve (I), depending on the pressure in the coronary vessels, is between the straight line corresponding to the coronary blood flow with maximally dilated vessels (A, B) and the curve of the magnitude of the coronary blood flow with normal vascular tone (the area of autoregulation). Under normal conditions, with intact coronary arteries, the heart is in a “superperfusion” situation, ie. delivery of О 2 slightly exceeds the level of PMO 2.
Rice. 2. Diagram of the coronary reserve and its dynamics depending on various pathological conditions of the CVS.
The diagram shows that the coronary reserve can change in the direction of increase or decrease depending on the physiological conditions or pathology from the coronary vessels, blood, myocardial mass. In a person at rest, the coronary blood flow in the heart muscle is 80-100 ml / 100 g / min, and about 10 ml / 100 g / min of O 2 is absorbed.
When the coronary arteries are damaged by atherosclerosis or as a result of inflammatory changes in the vascular wall, the ability of the latter to maximize dilatation (expansion) is sharply reduced, which entails a decrease in the coronary reserve.
Conversely, with an increase in the mass of the myocardium (left ventricular hypertrophy - AH, hypertrophic cardiomyopathy) or a decrease in the level of hemoglobin, a carrier of O 2, for adequate provision of PMO 2, an increase in coronary blood flow in the autoregulation area (movement of the autoregulation curve upward) is necessary, which leads to a decrease coronary reserve (II), especially in atherosclerotic lesions of the coronary vessels (B - decrease in the straight line, which characterizes the dilatation ability). In general terms, the coronary reserve diagram gives an idea of the mechanisms that ensure the correspondence between the changing levels of PMO 2, depending on the intensity of cardiac activity and the amount of O 2 delivery.
Acute coronary insufficiency is an acute discrepancy between the delivery of O 2, determined by the amount of coronary blood flow, and the level of PMO 2. (Fig. 3).
This discrepancy can be due to various reasons:
1 - a sharp drop in coronary blood flow as a result of thrombus formation, spasm (complete or partial occlusion) of the coronary arteries against the background of normal PMO 2;
2 - exothermic increase in PMO 2, exceeding the value of the coronary reserve;
3 - limited coronary reserve with a physiological increase in the level of PMO 2;
4 - multidirectional changes in the magnitude of coronary blood flow (decrease) and the level of PMO 2 (increase).
Rice. 3. Diagram of the ratio of the values of oxygen consumption by the myocardium (PMO 2) and the volume of coronary blood flow (Q)
At the beginning of the development of acute coronary insufficiency, it is possible to identify factors that affect the level of PMO 2 and the amount of coronary blood flow; by etiology - coronary, myocardial, extracardiac factors.
Of course, such a division is conditional, since in the conditions of an integral organism, to one degree or another, all factors are involved.
Animal studies have shown that ischemic or hypertrophied myocardium is more sensitive than the myocardium of a healthy heart, even to a slight decrease in hemoglobin levels. This negative effect of anemia on heart function has also been noted in patient studies. At the same time, a decrease in hemoglobin levels is accompanied by a decrease in blood oxygenation in the lung, which also contributes to a decrease in oxygen delivery to the myocardium.
Clinical observations indicate that with a reduced coronary reserve, ischemic, chronic myocardial dysfunction (systolic-diastolic) can form even against the background of a normal volume of coronary blood flow at rest.
More recently, the generally accepted clinical forms of ischemic heart disease included:
1 - angina pectoris of rest and tension,
2 - unstable angina,
3 - acute coronary syndrome (pre-infarction state),
4 - myocardial infarction; which, from the standpoint of today's understanding of pathological processes in an ischemic attack, cannot explain a number of conditions that general practitioners, cardiologists and, in particular, cardiac surgeons encounter in the clinic.
At present, based on the data obtained during pathophysiological studies in experiment and clinical observations, from the standpoint of cellular - subcellular and molecular mechanisms of the functioning of cardiomyocytes, a modern understanding of "new ischemic syndromes" has been formulated - "stunned myocardium" ("Muosadil Stunning"), "hibernating - asleep myocardium "(" Muosadil Hybernatin ")," preconditioning "," preconditioning - the second window of protection "(" Second Window Of Protection - SWOP ").
For the first time, the term "new ischemic syndromes", combining the above described conditions of the myocardium after various episodes of ischemia, reflecting adaptive-maladaptive changes in metabolism and contractile state of cardiomyocytes, was proposed by the South African cardiologist L.H. Opie in 1996 at a meeting of the International Society of Cardiology in Cape Town, sponsored by the Council for Molecular and Cellular Cardiology.
L.H. Opie emphasizes that - “in patients with coronary artery disease, the clinical picture of the disease is often characterized by 9-10 clinical syndromes, which are due to heterogeneity of causes and a variety of adaptive mechanisms.
Taking into account the heterogeneity of the manifestation of the ischemic episode, the unpredictability of the development and functioning of collateral circulation in the myocardium, as the first stage of myocardial protection, when the blood circulation in the coronary region is stopped, it can be assumed that even two identical patients cannot exist, in which the pathophysiology and clinical course of the disease would be absolutely the same. In one and the same patient, various adaptive mechanisms of "new ischemic syndromes" can be combined and formed.
In 1996, RW. Hochachka and colleagues suggested that the viability of the myocardium under ischemic conditions is provided by adaptation to hypoxia, which can be divided into two stages depending on the duration of the ischemic "attack" - a short-term defense reaction and a "survival" phase.
From the point of view of modern understanding of pathophysiological processes, it looks like this. During the transition to anaerobic glycolysis, at the stage of a short-term adaptation period, the reserves of high-energy phosphates (ATP, KrF) in the myocardium are depleted, which are always not large. This is accompanied, first of all, by a violation of the diastolic phase of relaxation of the cardiomyocyte and, as a consequence, a decrease in the contractile function of the myocardium in the area of ischemia.
Under physiological conditions, 10% ATP is formed during oxidative phosphorylation in mitochondria due to aerobic glycolysis (the breakdown of glucose to pyruvate). This amount of ATP, formed as a result of aerobic glycolysis, is not enough to ensure the functioning of the ionic calcium, sodium and potassium channels of the sarcolemma and, in particular, the calcium pump of the sarcoplasmic reticulum (SRS).
Replenishment of the rest of the amount of energy for the functioning of the cardiomyocyte with normal oxygen supply occurs due to the oxidation of free fatty acids (FFA), the breakdown of which during oxidative phosphorylation provides up to 80% of ATP. However, FFA, in comparison with glucose, is a less effective source of ATP - "fuel" for the heart - pump, since when they are oxidized, about 10% more oxygen is required to produce the same amount of ATP. A pronounced imbalance between the oxygen demand during the oxidation of glucose and FFA towards the latter leads to the fact that during ischemia (a sharp drop in oxygen delivery), a large number of under-oxidized active forms of fatty acids accumulate in the mitochondria of cardiomyocytes, which further aggravates the uncoupling of oxidative phosphorylation. (Fig. 4).
Underoxidized active forms of fatty acids, in particular - acylcarnitine, acylCoA, as metabolites, block the transport of ATP from the place of synthesis in mitochondria to the place of their consumption inside the cell. In addition, the increased concentration of these two metabolites in mitochondria has a destructive effect on the membrane of the latter, which further leads to a deficiency of energy necessary for the vital activity of the cardiomyocyte. In parallel, an excessive amount of protons (Na +, H +) accumulates in the cell against the background of anaerobic metabolism, i.e. its "acidification" occurs.
Further, Na +, H + are exchanged for other cations (mainly Ca ++), which results in an overload of Ca ++ myocytes, which is involved in the formation of contracture contraction. An excessive amount of Ca ++, a decrease in the functional capacity of the calcium pump SPR (energy deficit) lead to impaired diastolic relaxation of the cardiomyocyte and the development of myocardial contracture.
Thus, the transition to the anaerobic oxidative process is accompanied by the activation of FAs (long-chain cetylcarnitine and acylCoA), which contribute to the uncoupling of oxidative phosphorylation, the accumulation of excess Ca ++ in the cytosol, a decrease in myocardial contractility and the development of contracture with "adiastolic". (Fig. 5).
Rice. 4. Diagram of energy balance distribution in cardiomyocyte during anaerobic metabolism
Rice. 5. Diagram of Ca cardiomyocyte overload during restoration of coronary blood flow.
The survival phase is the stage of myocardial self-preservation in conditions of prolonged ischemia. The most significant adaptive reactions of the myocardium in response to ischemia include the so-called "new ischemic syndromes": hibernation, stunnedness, preconditioning, preconditioning are the second window of protection.
The term "stunnedness" of the myocardium was first introduced by G.R. Heidricx et al in 1975; the concept " hibernation»In 1985 described by S.H. Rahimatoola; " preconditioning"- CE. Murry and his staff proposed in 1986, and " pre-conditioning - second window"- at the same time M.S. Marber et al and T. Kuzuya et al in 1993.
Deafening(Stunning) of the myocardium - the phenomenon of postischemic dysfunction of the myocardium in the form of impaired relaxation-contraction processes, clinically manifested in the form of suppression of the pumping activity of the heart, and persisting after the restoration of coronary blood flow for several minutes or days.
In an experiment on animals, a short period of time of an ischemic attack (stopping blood flow) from 5 to 15 minutes does not lead to the development of myocardial necrosis, however, ischemia lasting at least 5 minutes (a typical anginal attack) leads to a decrease in contractile function over the next 3 hours , and an ischemic attack within 15 minutes (without necrosis of the heart muscle) lengthens the recovery period of contractile function to 6 hours or more (Fig. 6).
A similar state of the myocardium in response to ischemic episodes occurs in 4 situations:
1 - in the boundary layers with necrosis of the heart muscle;
2 - after a temporary increase in PMO 2 in areas supplied with blood by a partially stenotic coronary artery;
3 - after episodes of subendocardial ischemia during excessive physical activity in the presence of left ventricular myocardial hypertrophy (normal coronary arteries);
4 - situation - "ischemia-reperfusion" (hypoxia of the heart muscle followed by reoxygenation).
Rice. 6. Schedule of recovery of myocardial contractility depending on the duration of ischemia.
Duration of coronary artery occlusion at least 1 hour is accompanied by " severe damage(maimed) myocardium" or " chronic stunnedness", Which is manifested by the restoration of the pumping function of the heart after 3-4 weeks.
A typical clinical manifestation of myocardial stunnedness is a feeling of "heavy, stone heart", which is based on impaired left ventricular diastole - "ineffective diastole".
At present, two theories of pathophysiological processes dominate in the formation of this phenomenon: A - the formation of an excess amount of free oxygen radicals during reperfusion, with the activation of lipid peroxidation; B - uncontrolled entry of Ca ++ and its excessive accumulation in the cardiomyocyte, as a result of damage to the sarcolemma by lipid peroxidation after reperfusion.
G.I. Sidorenko, summarizing the results of clinical observations, distinguishes 4 clinical variants of myocardial stunnedness, depending on the root cause of the violation of the correspondence of PM0 2 to the value of coronary blood flow (Q to p # PMO 2): atrial - posttachycardiomyopathic, microvascular and non-restored blood flow syndrome - "reflow" ...
Atrial stunning occurs in the period after cardioversion, posttachycardiomyopathy is a condition accompanied by a decrease in the pumping function of the heart after the restoration of normosystole; microvascular dysfunction is a reduced competence of microcirculation due to ineffective (incomplete) coronary recanalization; reflow syndrome - non-restoration of blood flow at the level of microcirculation (DIC stage I - thrombotic).
The mechanism of myocardial “stunning” development is not fully understood: the leading factors in the “Stunning” pathogenesis are at least three factors: the formation of an excessive amount of ROS, postperfusion calcium overload of cardiomyocytes, and a decrease in the sensitivity of myofibrils to calcium.
It has been shown that in approximately 80% of cases the formation of the phenomenon of "myocardial hibernation" is due to the action of ROS, in 20% - calcium overload, which is realized through the sequential inclusion of Na + / H + and Na + / Ca ++ exchangers. ROS may participate in the formation of calcium overload through damage to proteins involved in the intracellular kinetics (transport) of Ca ++. In turn, the calcium overload of the myoplasm can activate calpins - enzymes that cause proteolysis of myofibrils. The need for resynthesis of new myofillas is one of the factors determining the duration of restoration of the contractile function of cardiomyocytes.
Reversible myocardial damage caused by the accumulation of free radicals in the myocardium, when the myocardium is stunned, is manifested either as a direct effect of free radicals on myofibrils with damage, or indirectly through the activation of proteases, followed by degradation of myofibril proteins.
Another mechanism of violations of the contractile function of cardiomyocytes in stunned myocardium is the accumulation of an excess amount of cytosolic Ca - an increase in the intracellular concentration of ionized calcium (Ca ++).
After the restoration of blood flow, there is an excess, not regulated by calcium channels, the flow of Ca through the damaged sarcolemma. Deficiency of macrophosphate energy does not ensure the work of the calcium pump of the sarcoplasmic reticulum (SRS), which regulates the cytoplasmic concentration of Ca. The lack of ATP in myofibrils manifests itself in two ways: persisting unopened connecting bridges between actin and mossin (incomplete diastole) reduce the number of possible interaction sites, which further limits the mutual movement of myofilaments in the sarcomere (contraction).
Thus, an excess amount of cytosolic calcium contributes to the development of incomplete diastole, the development of myocardial contracture.
Cell survival during a certain period of ischemia is possible due to the existence of a number of protective mechanisms aimed primarily at limiting the consumption of ATP in myofibrils. These mechanisms are realized through a decrease in the Ca ++ entry into the cardiomyocyte and a decrease in the sensitivity of the contractile apparatus to it.
Microvascular disorders, in most cases of a secondary nature, due to the aggregation of blood corpuscles (platelets, erythrocytes, leukocytes) against the background of myocardial contracture, also take part in maintaining the stunned myocardium.
"Myocardial hibernation"- adaptive decrease in intracellular energy metabolism, by inhibiting the contractile state of the cardiomyocyte, in response to a decrease in coronary blood flow.
Hibernation(Hybernatin) myocardium, as defined by Professor S.N. Rahimatoola (1999) - a rapidly emerging violation of local contractility of the left ventricle in response to a moderate decrease in coronary blood flow. The hibernating myocardium is characterized by a chronic decrease in the contractility of cardiomyocytes with their preserved viability. From the point of view of pathophysiological processes of adaptation to stressful situations, "hibernating myocardium" is "a self-regulation mechanism that adapts the functional activity of the myocardium to ischemic conditions", i.e. a kind of protective reaction of the "suffering heart" to an inadequate decrease in coronary blood flow to the level of PMO 2. This term, "hibernating (sleeping) myocardium" S.H. Rahimatoola was first proposed in 1984 at the IHD Workshop at the US National Heart, Lung, and Blood Institute.
The authors, using thallium scintigraphic technique, revealed from 31 to 49% of viable tissue in areas with irreversibly reduced contractile function of the left ventricular myocardium. That is, in places of reduced local blood flow, relatively normal metabolic activity remains - the myocardium is viable, but it cannot provide a normal regional ejection fraction. In this case, there are clinical symptoms of ischemia, but which do not end with the development of myocyte necrosis. In the clinic, similar situations can occur with stable and unstable angina pectoris, in patients with CHF.
According to E.V. Carlson et al, published in 1989, in patients undergoing effective coronary angioplasty, myocardial hibernation sites are detected in 75% of cases among patients with unstable angina pectoris and in 28% of cases with stable angina pectoris. The minimization of metabolic and energy processes in the heart muscle while maintaining the viability of myocytes allowed some researchers to call this situation either “Smart Heart”, or “Self-preservation Heart” or “Playing Heart” ... Italian researchers defined a similar condition of the heart muscle as "myocardial lethargy."
The mechanisms of hibernation are poorly understood. In clinical practice, against the background of a reduced coronary reserve, the gradual development of destructive changes in the hibernating myocardium is a consequence of cumulative shifts in energy exchange in response to periodic inotropic stimulation.
In conditions of limited blood flow, a positive inotropic response is achieved due to the depletion of the metabolic status of the cardiomyocyte. Thus, gradually accumulating metabolic changes can cause disorganization of the intracellular structures of the heart muscle.
Preconditioning(Preconditioning) - metabolic adaptation to ischemia, after repeated short-term episodes of decreased coronary blood flow, manifested by increased resistance of the heart muscle to a subsequent, more prolonged ischemic attack.
Preconditioning is a favorable change in the myocardium caused by rapid adaptive processes during a short episode of ischemic attack on the myocardium, followed by rapid restoration of blood flow (reperfusion), which protect the myocardium from ischemic changes until the next episode of ischemia / reperfusion. This phenomenon is phylogenetically determined and is typical for all organs of the mammalian organism.
In 1986, in experimental conditions on dogs, CE. Murry et al. Have convincingly demonstrated that repeated short episodes of regional myocardial ischemia adapt the heart muscle to the next episodes of ischemic attacks, which is documented by the preservation of intracellular ATP at a sufficient level for cardiomyocyte functioning, with the absence of necrotic cell damage.
In other experiments, it was shown that preliminary intermittent 5-minute episodes of coronary artery occlusion followed by 5-minute intervals of reperfusion (ischemia / reperfusion) lead to a 75% decrease in the size of ischemic necrosis of the heart muscle (compared with a control group of dogs, which a kind of 5-minute training was not carried out - ischemia / reperfusion) in response to the cessation of blood circulation for 40 minutes.
Such a capradioprotective effect of short-term episodes of ischemia / reperfusion was defined as “ischemic preconditioning”, while the absence of the development of the phenomenon of “reperfusion syndrome” was noted. This protective phenomenon was later identified by R.A. Kloner and D. Yellon (1994) in clinical practice.
Previously, it was believed that the cardioprotective effect of ischemic preconditioning manifests itself immediately after short-term episodes of ischemia / reperfusion, and then loses its protective properties after 1-2 hours. In 1994 D. Yellon in collaboration with G.F. Baxter showed that the phenomenon of "post-ischemic preconditioning" can re-develop after 12-24 hours with a duration of up to 72 hours, but in a weakened form. A similar, distant phase of tolerance to ischemic myocardial injury was defined by the authors as "Second window of protection" (« S econd W indow O f P rotection - SWOP"), In contrast to the early" classical ischemic preconditioning ".
Clinical situations of “classical ischemic preconditioning” are the “warm-up Phenomen” or “Walk-Through-Angina” syndrome, which manifest itself in a gradual decrease in the frequency and intensity of anginal attacks during ongoing moderate physical or household activity.
The phenomenon of "pacing" is based on the rapid adaptation of the myocardium to the load against the background of a decrease in the ratio - Qcor / PMO 2 after the second episode of ischemia. G.I. Sidorenko notes that this syndrome is observed in almost 10% of patients with angina pectoris, and the ST segment on the standard ECG, elevated during the first attack, decreases to the isoline, despite the continued load. (Fig. 7).
A similar picture is observed in a number of cases during exercise testing, when stenocarditis pain and / or displacement of the ST segment appears at the height of the load, and when it continues, they disappear. Such situations made it possible to formulate such concepts as "primary hidden angina" (First Holeangina) or "angina pectoris of the first load" (First - Effort-Angina).
Rice. 7. Effect of "Preconditioning" - initial ECG (a), coronary artery spasm against the background of moderate exercise with ST elevation on the ECG (b) and ECG recovery (c) against the background of continuing moderate exercise
It is possible that ischemic preconditioning underlies the fact that patients with preinfarction angina tend to have a more favorable prognosis compared to those patients who developed myocardial infarction against the background of previous complete well-being.
It has been shown that attacks of angina pectoris (pre-infarction angina pectoris) preceding the development of myocardial infarction can have a protective effect on the myocardium (reduction of the affected area) if they occurred within 24-48 hours before the development of myocardial infarction. Such observations in clinical practice resemble the cardioprotective effect of long-term ischemic preconditioning ("second window of protection") in animal experiments.
Phenomenon "Lack of restoration of blood flow in intramural to subendocardial coronary arteries"(no-reflow) - a significant decrease in coronary blood flow in patients with coronary artery disease against the background of vascular lesions and reperfusion, despite the complete restoration of patency (recanalization) in the epicardial coronary arteries.
There is evidence that in clinical practice, preinfarction angina is able to reduce the "no-reflow" phenomenon, thereby protecting the myocardium from ischemia and reperfusion caused by microvascular lesions in the heart. This reduces the risk of developing myocardial infarction or its size, improves the restoration of the pumping function of the left ventricle in cases of its damage, and also significantly reduces the risk of in-hospital mortality.
The cardioprotective role of preinfarction angina can be explained by a number of mechanisms:
1 - protection of late postischemic preconditioning;
2 - disclosure of collateral circulation;
3 - increased sensitivity to thrombolysis.
The effect of ischemic preconditioning on the size of myocardial infarction and on the degree of preservation of its functional state (pumping function of the heart) after myocardial infarction depends on many factors, including the severity of collateral coronary blood flow, and the duration of the time interval between the onset of ischemia and treatment.
When carrying out myocardial revascularization using coronary artery bypass grafting using the activation of postischemic preconditioning (two cycles of 3-minute total cardiac ischemia using temporary clamping of the ascending aorta under cardiopulmonary bypass, followed by 2-minute periods of reperfusion, 10 minutes before global myocardial ischemia), a decrease in the severity of necrotic myocardial damage was noted.
In another study, when post-ischemic preconditioning was activated (clamping the aorta for 1 minute followed by reperfusion for 5 minutes before cardiac arrest), after CABG, it resulted in a significant increase in cardiac output (CI) and a decrease in the need for inotropic drugs to be administered to patients.
The formation of postischemic preconditioning is due to the inclusion of many complex adaptation mechanisms, of which two are currently more studied: A - a decrease in the accumulation of glycogen breakdown products and adenine nucleotides by cardiomyocytes, such as H +, NH3 ions, lactate, inorganic phosphates, adenosine; B - an increase in the activity or synthesis of enzyme systems that have a cardioprotective effect from ischemic damage.
Table 1 shows the most studied endogenous and exogenous mediators and mechanisms for the implementation of the action of ischemic preconditioning. In 2002, Y.R Wang and colleagues presented convincing evidence of a cardioprotective effect in the late preconditioning phase, an increase in NO production by stimulating the production of its synthase ( I nducible S yntase NO- iNOS).
It is known that the induced NO synthase isoform is found in many cells of the body, in particular, in cardiomyocytes, vascular smooth muscle cells, and macrophages. They are instantly activated under the influence of a number of pro-inflammatory factors such as the cytokines IL-1B, IL-2, IFN-g, TNF-b and others. Adenosine, acetylcholine, bradykinin, lipopolysaccharides, opioids, free radicals, and serotonin can take part as endogenous mediators that trigger the activation and synthesis of iNOS.
Restoration of coronary blood flow (reperfusion) is accompanied by the "washing out" of the products of anaerobic energy metabolism from the ischemic area of the myocardium, which restrain the contractile activity of cardiomyocytes, and the "surging" supply of oxygen causes a kind of "explosion" in the formation of reactive oxygen species - secondary free radicals (hydroxyl - HO - , lipoxyl - LO -).
Reperfusion removal of inhibition of contraction activation by "washing out" of adenosine, K +, H + is accompanied by a rapid recovery of myocardial contractile function, using the available reserves of CrF and ATP. The degree of further reduction depends on the state of mitochondria, which provide the synthesis of phosphate macroergs by oxidative phosphorylation. The resumption of aerobic resynthesis of ATP and its rate are determined by the degree of preservation of the electron transport chain and cycle enzymes
Table 1. Endogenous mediators of ischemic preconditioning mechanisms
|
Endogenous mediators of preconditioning |
|
|
Mediators |
Mechanisms of action |
|
Adenosine |
Via adenosine A and tyrosine kinase |
|
Acetylcholine |
Protein kinase activation |
|
Opioids (Morphine) |
S-opioid receptor activation |
|
Norepinephrine |
Activation - a - adrenergic receptor |
|
Serotonin |
Vasodilating effect? |
|
Activation of K-ATP-sensitive channels |
|
|
Cytokines IL-1B, IL-2 | |
|
By expressing iNOS stimulation |
|
|
Antioxidants - Effect on Reactive O 2 Species |
By expressing iNOS stimulation |
|
External incentives |
|
|
Lipopolysaccharides (bacterial endotoxin) |
Promotes the production of Heat Shok Protein 70i (hsp 70i) affecting the myocardium. |
|
Monophospholipid (MLA) |
INOS gene induction |
|
Pharmacological substances |
Increased expression of C-jun c-tos mRNA catalase and mn-containing dismutase |
|
K + -channel activators: dimacaine, cromacalin, nicorandil |
Are direct "openers of ATP-sensitive K + -channels |
Krebs in mitochondria. In the presence of damage to mitochondria, and therefore part of the oxidative phosphorylation chain, the rate of ATP synthesis may lag behind the needs of the contractile apparatus and the restoration of the contractile function will be inadequate.
The task - the initial restoration of myocardial energy reserves - has been the subject of study over the past two decades, which have shown that not ATP, but KrF is the main energy substrate that determines the level of contractile function, the consumption and recovery of which take place primarily after reperfusion.
For example, in the "hibernating myocardium" (against the background of a reduced functional state), the level of ATP is moderately reduced. Unlike ATP, the CRF level can be restored much faster, because the creatine required for its synthesis leaves the cell more slowly than adenosine, which is the basis of ATP. However, the restoration of the contractile function of the cardiomyocyte as a result of a rapid increase in the intracellular concentration of CRP is limited by the ATP molecules involved in the regulation of the ion transport of cardiomyocytes.
At present, based on the data of different-level studies, a hypothesis has been formulated about the mechanisms of the protective action of classical ischemic preconditioning, the essence of which is associated with modifications of intracellular metabolism - the maintenance of a sufficiently high level of ATP by limiting the utilization of high-energy phosphates.
Ischemic preconditioning is triggered by the interaction of endogenous factors (triggers) with their specific receptors.
Triggers - biological active substances released from cardiomyocytes during ischemic episodes and reperfusion (adenosine, bradykinin, prostanoids, catecholamines, endorphins, NO, ROS, etc.), realize their effects by different pathways of intracellular signaling (Fig. 8, 9).
Rice. eight. Energy exchange during a short attack of ischemia (A) and intracellular signaling pathways activated by adenosine during ischemic preconditioning (B): FLS - phospholipase, DAG - diacylglycerol, F - phosphate, PCS - protein kinase, IFZ - inositol triphosphate
Rice. nine. Intracellular signaling pathways activated by bradykinin during ischemic preconditioning: NO - nitrous oxide, PDE - phosphodiesterase, GTP - guanesine triphosphate, cGMP - cyclic guanesine monophosphate, cAMP - cyclic adenosine monophosphate
The hypothesis of the participation of the trigger system in the start of ischemic preconditioning is based on the following facts revealed in the experiments:
- Intracellular concentration of triggers increases with ischemia;
- Its introduction into the coronary bed or non-ischemic myocardium produces a protective effect similar to ischemic preconditioning;
- Administration of trigger inhibitors blocks the cardioprotective effect of ischemic preconditioning.
Based on the essence of the action of factors - natural limiters of the contractile function of the myocardium when the coronary blood flow is stopped, it can be assumed that the preservation of their influence after reperfusion should be accompanied by a more complete restoration of the pumping activity of the heart.
The above shows that in order to reduce myocardial damage during postischemic reperfusion, it is necessary to ensure the restoration of energy reserves to the initial level and to prevent excessive ROS formation.
Various modifications of reperfusion solutions with calcium antagonists (magnesium preparations), increased potassium concentration, with the addition of metabolites that contribute to the accelerated synthesis of adenine nucleotides, can improve the restoration of the pumping function of the heart after ischemia.
To solve another problem - to reduce the excessive formation of ROS - it is possible to use reperfusion solutions with antihypoxants and antioxidants (Actovegin).
Finally, the third approach is to mobilize one's own defense mechanisms that are activated during ischemic episodes (the basis of the “preconditioning effect”), when a series of periods of short ischemia (pain syndrome no more than 5 minutes) is combined with periods of blood flow restoration - pain relief with organic nitrates sublingually.
Recent studies have found the existence of a "second window of protection" or late ischemic preconditioning.
In contrast to classical ischemic preconditioning, the protective effects of which are manifested immediately after short-term episodes of ischemia / reperfusion, late ischemic preconditioning is detected in a day or more with a prolonged and less intense response. The mechanisms of this form of ischemic preconditioning are due to the inclusion of gene expression for the synthesis of "heat shock" proteins and cellular iNO synthase.
There are opinions that the protective effect of the “second window” of preconditioning is mediated precisely through an increase in the formation of primary ROS, in particular, NO, during prolonged ischemia, which is blocked by macrophage oxygen radical scavengers (scavenger receptors) and iNO synthase inhibitors.
Many different factors are involved in the mechanisms of the development of the protective effect of ischemic preconditioning, but, according to the latest data, the leading role is played by mitochondrial Ca ++ - activated K + - channels realized through their influence on changes in the electron transport chains of mitochondria. There is ample evidence that the pharmacological discovery of AFT-dependent K + channels fully reproduces the protective effect of ischemic preconditioning.
Mitochondrial ATP-dependent K + -channels are more sensitive than similar channels of the sarcolemma to opening and closing signals
It is believed that the energy-saving effect of ischemic preconditioning is due to a decrease in the activity of the proton mitochondrial F0 F1 ATPase, which dephosphorylates the main amount of ATP during ischemia. The activity of this enzyme is inhibited by the IF1 protein, which is synthesized in response to ischemia with an increase in its affinity for ATPase in acidosis. Other reasons may be a decrease in the activity of enzymes catalyzing ATP-dependent metabolic reactions, less use of ATP by myofibrillar ATPase as a result of "Stunning", a decrease in the activity of sarcolemmal Na +, K + - ATPase, Ca ++ - ATPase of the sarcoplasmic reticulum.
The consequence of less utilization and degradation of high-energy phosphates (CrP, ATP) during prolonged ischemia is a decrease in intracellular acidosis, since the main source of H + is the breakdown of ATP. With ischemic preconditioning, less accumulation of under-oxidized glycolysis products (pyruvates, phosphoglycerates, lactates, etc.) is recorded, which contributes to the maintenance of plasma osmolarity at an acceptable level and prevents intracellular edema of cardiomyocytes.
It was shown that within a short time of classical preconditioning, there is no activation of genes responsible for the resynthesis of intracellular proteins of cardiomyocytes. At the same time, the formation of "Heat shock" proteins, iNO synthase, superoxide dismutase and some key enzymes of energy metabolism are essential conditions for the manifestation of cardioprotective effects of the "second window".
It is assumed that, in addition to the formation of proteins, the mechanisms of action of the “second window” of preconditioning also include the generation of free radicals of oxygen and peroxynitrite, a product of the interaction between NO and O 2 - (ONOO -). This is supported by the fact that pre-administration of free radical scavengers before episodes of short ischemia block the protective effects of delayed preconditioning.
A new strategy in the pharmacological protection of the heart from ischemic and reperfusion injuries is the use of inhibitors of the Na + / H + transporter in the sarcolemma. Under normal conditions, the sarcolemmal Na + / H + - exchanger is not activated. During ischemia, in response to rapidly developing intracellular acidosis and, possibly, to other stimulating factors, its activity increases.
This leads to an increase in the intracellular concentration of Na + ions, which is also facilitated by the inhibition of Na + / K + - ATPase - the main mechanism of Na ++ excretion from the myocyte. In turn, with the accumulation of Na + ions, the entry of Ca ++ ions into the cell through the Na + / Ca ++ - exchanger increases, which contributes to the "Ca ++ - overload". (Fig. 5).
Inhibitors of Na + / H + - exchange exert their cardioprotective effect during ischemia, partially blocking this sequence of ion exchange during ischemia. Ischemic preconditioning is able to block the Na + / H + -exchanger for a long period of ischemia, reducing the overload of ischemic cardiomyocytes with Na + and Ca ++ ions at the stage of early reperfusion. To date, several groups of inhibitors have been synthesized with extremely high affinity for the Na + / H + - transporter and low - for the Na + / Ca ++ - exchanger and Na + / HCO 3? - to the symporter.
Using nuclear magnetic resonance and fluorescent dyes, it was shown that blocking the Na + / H + - carrier is accompanied by a decrease in the frequency of reperfusion arrhythmias and support of ionic hemostasis in the ischemic myocardium. At the same time, a decrease in the formation and release of inorganic phosphates into the interstitium - products of ATP degradation, a better preservation of the intracellular fund of high-energy phosphates, a lower accumulation of Ca ++ in the mitochondrial matrix and a decrease in damage to the ultrastructure of cardiomyocytes were recorded.
Nowadays, inhibition of the Na + / H + - carrier has become a method of protecting the heart, which is increasingly used in the clinic, these include 4-isopropyl-3-methylsulfonylbenzoylguanidine methanesulfonate(Cryporis, NOE 642).
In clinical practice, the protective effect of ischemic preconditioning is documented by a non-pharmacological decrease in the ST segment elevation on the ECG with continued test load.
Thus, myocardial ischemia is a failure of the delivery of blood oxygen to the myocardium to the requirements of aerobic synthesis of adenosine triphosphate in mitochondria to ensure normal heart function at a given heart rate, preload, afterload and contractile state of the heart muscle. With oxygen deficiency, the anaerobic pathway of ATP synthesis is activated through the splitting of glycogen stores with the accumulation of lactate, a decrease in the intracellular pH level and an overload of cardiomyocytes with calcium ions, manifested by diastolic-systolic dysfunction.
Periods of ischemic episodes are accompanied by successive stages of metabolic adaptation - the implementation of various pathways of intracellular metabolism ("ischemic preconditioning"), functional adaptation - a decrease in myocardial contractile function according to the level of energy phosphates ("myocardial hibernation"), followed by biological rehabilitation - restoration of contractile function ("myocardial stunnedness" ) or death of myocardial cells (apoptosis) (Fig. 10).
Rice. ten.
Myocardial infarction. A.M. Shilov
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