What is the pericardium and its function. How does pericarditis affect heart health. What are the symptoms of pericardial problems. How are pericardial disorders diagnosed and treated.

The Pericardium: The Protective Sac Around Your Heart

The pericardium is a crucial component of the cardiovascular system, yet many people are unaware of its existence and importance. This membranous sac envelops the heart, playing a vital role in its function and protection. Understanding the pericardium and its associated disorders is essential for maintaining optimal heart health.

The pericardium serves several important functions:

• It anchors the heart within the chest cavity
• It provides a frictionless environment for the heart to beat efficiently
• It acts as a barrier against infection and inflammation
• It limits excessive dilation of the heart during sudden increases in blood volume

When the pericardium becomes inflamed or damaged, it can lead to various pericardial disorders, with pericarditis being the most common.

Pericarditis: Inflammation of the Heart’s Protective Layer

Pericarditis is the inflammation of the pericardium, which can occur due to various factors. This condition can be acute (short-term) or chronic (long-term), and its severity can range from mild to life-threatening.

Causes of Pericarditis

Pericarditis can be triggered by several factors, including:

• Viral infections (most common cause)
• Bacterial or fungal infections
• Heart attacks
• Autoimmune disorders
• Chest injuries
• Certain medications
• Radiation therapy
• Kidney failure

In some cases, the exact cause of pericarditis remains unknown, a condition referred to as idiopathic pericarditis.

Recognizing the Symptoms of Pericardial Problems

Identifying pericardial issues early is crucial for prompt treatment and prevention of complications. The symptoms of pericardial problems can vary depending on the specific condition and its severity.

Common Symptoms of Pericarditis

• Sharp, stabbing chest pain, often worsening when lying down or breathing deeply
• Rapid heartbeat (tachycardia)
• Difficulty breathing or shortness of breath
• Fever (especially in acute pericarditis)
• Fatigue and weakness
• Dry cough
• Swelling in the legs or abdomen

Are these symptoms always indicative of pericarditis? While these symptoms are common in pericardial disorders, they can also be present in other heart conditions. Therefore, it’s essential to consult a healthcare professional for an accurate diagnosis.

Pericardial Effusion: When Fluid Accumulates in the Pericardial Sac

Pericardial effusion is a condition characterized by an abnormal accumulation of fluid in the pericardial space. This buildup can occur gradually or suddenly and may be caused by various factors, including:

• Inflammation (pericarditis)
• Infection
• Cancer
• Kidney failure
• Hypothyroidism
• Trauma

The severity of pericardial effusion depends on the amount of fluid accumulated and how quickly it develops. In some cases, it can lead to a life-threatening condition called cardiac tamponade.

Cardiac Tamponade: A Medical Emergency

Cardiac tamponade occurs when the fluid buildup in the pericardial sac puts pressure on the heart, preventing it from filling properly. This can lead to a dramatic drop in blood pressure and potentially fatal consequences if not treated promptly.

Symptoms of cardiac tamponade include:

• Chest pain
• Difficulty breathing or rapid breathing
• Dizziness or fainting
• Weak or absent pulse
• Bluish skin color

How is cardiac tamponade treated? Immediate medical attention is crucial. Treatment typically involves draining the excess fluid through a procedure called pericardiocentesis, which can provide rapid relief and prevent further complications.

Diagnosing Pericardial Disorders: From Physical Exams to Advanced Imaging

Accurate diagnosis of pericardial disorders is essential for appropriate treatment. Healthcare providers employ various diagnostic tools and techniques to identify and assess pericardial problems.

Physical Examination

The initial step in diagnosing pericardial disorders often involves a thorough physical examination. During this exam, the doctor may:

• Listen to heart sounds using a stethoscope
• Check for signs of fluid retention in the legs or abdomen
• Assess breathing patterns and lung sounds
• Evaluate overall appearance and vital signs

Diagnostic Tests

To confirm a diagnosis and determine the severity of the condition, various tests may be ordered:

1. Electrocardiogram (ECG): This test records the heart’s electrical activity and can reveal changes indicative of pericarditis.
2. Chest X-ray: It can show an enlarged heart silhouette, suggesting fluid accumulation in the pericardium.
3. Echocardiogram: This ultrasound of the heart can visualize pericardial effusion and assess its impact on heart function.
4. CT scan or MRI: These imaging techniques provide detailed views of the heart and pericardium, helping to identify inflammation, thickening, or fluid accumulation.
5. Blood tests: These can detect signs of inflammation, infection, or other underlying conditions that may be causing pericardial problems.

In some cases, a procedure called pericardiocentesis may be performed for both diagnostic and therapeutic purposes. This involves inserting a needle into the pericardial space to remove fluid for analysis and relieve pressure on the heart.

Treatment Approaches for Pericardial Disorders

The treatment of pericardial disorders varies depending on the underlying cause, severity, and specific condition. The primary goals of treatment are to relieve symptoms, reduce inflammation, and prevent complications.

Medications

Common medications used in treating pericardial disorders include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs): These are often the first-line treatment for acute pericarditis to reduce pain and inflammation.
• Colchicine: This medication can be used in combination with NSAIDs to treat acute pericarditis and prevent recurrence.
• Corticosteroids: In cases where NSAIDs and colchicine are ineffective or contraindicated, corticosteroids may be prescribed to reduce inflammation.
• Antibiotics: If a bacterial infection is the cause, appropriate antibiotics will be prescribed.

Pericardiocentesis

For pericardial effusion or cardiac tamponade, pericardiocentesis may be necessary to drain excess fluid from the pericardial sac. This procedure can provide immediate relief and prevent further complications.

Pericardiectomy

In cases of recurrent or chronic pericarditis that doesn’t respond to other treatments, a surgical procedure called pericardiectomy may be recommended. This involves removing part or all of the pericardium to alleviate symptoms and prevent further complications.

What factors influence the choice of treatment? The selection of treatment depends on various factors, including the underlying cause, severity of symptoms, presence of complications, and the patient’s overall health status. A personalized treatment plan is essential for optimal outcomes.

Living with Pericardial Disorders: Lifestyle Modifications and Long-term Management

While many cases of pericarditis resolve with appropriate treatment, some individuals may experience recurrent or chronic pericardial disorders. In such cases, long-term management and lifestyle modifications are crucial for maintaining heart health and quality of life.

Lifestyle Recommendations

• Follow a heart-healthy diet rich in fruits, vegetables, whole grains, and lean proteins
• Engage in regular, moderate exercise as recommended by your healthcare provider
• Manage stress through relaxation techniques, meditation, or counseling
• Avoid smoking and limit alcohol consumption
• Get adequate rest and sleep
• Attend regular follow-up appointments with your cardiologist

Monitoring and Prevention

Individuals with a history of pericardial disorders should be vigilant about their heart health and take steps to prevent recurrence or complications:

• Be aware of symptoms and seek prompt medical attention if they recur
• Adhere to prescribed medication regimens
• Complete the full course of any prescribed antibiotics
• Consider getting vaccinated against influenza and pneumococcal infections, as these can trigger pericarditis in susceptible individuals

Can pericardial disorders be prevented entirely? While not all cases of pericardial disorders can be prevented, maintaining overall heart health and promptly addressing any underlying conditions can reduce the risk of developing these problems.

Emerging Research and Future Directions in Pericardial Disorder Management

The field of cardiology continues to evolve, with ongoing research aimed at improving our understanding and treatment of pericardial disorders. Several areas of investigation show promise for enhancing patient care and outcomes.

Immunotherapy

Researchers are exploring the use of targeted immunotherapies for treating recurrent and chronic pericarditis. These treatments aim to modulate the immune response and reduce inflammation more effectively than traditional medications.

Genetic Studies

Investigations into genetic factors that may predispose individuals to pericardial disorders are ongoing. This research could lead to more personalized approaches to prevention and treatment.

Advanced Imaging Techniques

The development of more sophisticated imaging technologies may allow for earlier and more accurate diagnosis of pericardial disorders, potentially improving treatment outcomes.

Minimally Invasive Procedures

Researchers are working on refining minimally invasive techniques for treating pericardial disorders, aiming to reduce recovery time and improve patient comfort.

How might these advancements impact patient care in the future? As research progresses, we can anticipate more targeted and effective treatments, improved diagnostic capabilities, and potentially even preventive strategies for individuals at high risk of pericardial disorders.

Understanding the pericardium and its associated disorders is crucial for maintaining heart health. By recognizing the symptoms, seeking prompt medical attention, and following appropriate treatment plans, individuals can effectively manage pericardial disorders and maintain a healthy, active lifestyle. As research continues to advance our knowledge in this field, we can look forward to even better outcomes for those affected by these conditions.

Pericarditis | Pericardial Disorders | MedlinePlus

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The pericardium is a membrane, or sac, that surrounds your heart. It holds the heart in place and helps it work properly. Problems with the pericardium include:

• Pericarditis – an inflammation of the sac. It can be from a virus or other infection, a heart attack, heart surgery, other medical conditions, injuries, and certain medicines.
• Pericardial effusion – the buildup of fluid in the sac
• Cardiac tamponade – a serious problem in which buildup of fluid in the sac causes problems with the function of the heart

Symptoms of pericardial problems include chest pain, rapid heartbeat, and difficulty breathing. Fever is a common symptom of acute pericarditis. Your doctor may use a physical exam, imaging tests, and heart tests to make a diagnosis. Treatment depends on the cause.

NIH: National Heart, Lung, and Blood Institute

• Heart Inflammation

  (National Heart, Lung, and Blood Institute)

• Myocarditis and Pericarditis after mRNA COVID-19 Vaccination

  (Centers for Disease Control and Prevention)

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• Acute Pericarditis

  (Merck & Co. , Inc.)

  Also in Spanish

• Chronic Pericarditis

  (Merck & Co., Inc.)

  Also in Spanish

• Dressler Syndrome

  (Mayo Foundation for Medical Education and Research)

  Also in Spanish

• Pericardial Effusion

  (Mayo Foundation for Medical Education and Research)

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• Pericarditis

  (Mayo Foundation for Medical Education and Research)

• Pericarditis

  (Texas Heart Institute)

  Also in Spanish

• ClinicalTrials. gov: Pericardial Effusion

  (National Institutes of Health)

• ClinicalTrials.gov: Pericarditis

  (National Institutes of Health)

• Article: Cardiac tamponades related to interventional electrophysiology procedures are associated with higher. ..

• Article: Cardiovascular toxicity profiles of immune checkpoint inhibitors with or without angiogenesis…

• Article: Recurrent pericarditis.

• Pericardial Disorders — see more articles

• American Heart Association

• National Heart, Lung, and Blood Institute

Function, Role in the Body, and Associated Conditions

What is the pericardium?

The pericardium is a thin sac that surrounds your heart. It protects and lubricates your heart and keeps it in place within your chest.

Problems can occur when the pericardium becomes enflamed or fills with fluid. The swelling can damage your heart and affect its function.

The pericardium has a few important roles:

• It keeps your heart fixed in place within your chest cavity.
• It prevents your heart from stretching too much and overfilling with blood.
• It lubricates your heart to prevent friction with the tissues around it as it beats.
• It protects your heart from any infections that might spread from nearby organs like the lungs.

The pericardium has two layers:

• Fibrous pericardium is the outer layer. It’s made from thick connective tissue and is attached to your diaphragm. It holds your heart in place in the chest cavity and protects from infections.
• Serous pericardium is the inner layer. It’s further divided into two more layers: the visceral and parietal layers. The serous pericardium helps to lubricate your heart.

In between these two layers is the fluid-filled pericardial cavity. It lubricates the heart and protects it from injury.

Pericardial effusion is the buildup of too much fluid between the pericardium and your heart. This can happen from damage or disease in the pericardium. Fluid can also build up if there’s bleeding in your pericardium after an injury.

Possible causes of pericardial effusion include:

• diseases that cause inflammation, such as lupus or rheumatoid arthritis
• severe underactive thyroid (hypothyroidism)
• infections
• recent heart surgery
• cancer that has spread to your pericardium
• kidney failure

Symptoms of pericardial effusion include:

• chest pressure or pain
• shortness of breath
• difficulty breathing when you lie down
• nausea
• a feeling of fullness in your chest
• trouble swallowing

The excess fluid from pericardial effusion can cause intense pressure on your heart and damage it.

A pericardial cyst is a noncancerous, fluid-filled growth in the pericardium. This type of cyst is very rare, affecting only 1 in 100,000 people.

Most people who have pericardial cysts are born with them, but they often aren’t diagnosed until they reach their 20s or 30s.

Pericardial cysts are usually found during a chest X-ray that’s done for another reason since these cysts don’t cause symptoms on their own.

Symptoms may only appear when the cyst presses on nearby organs or structures, and can include:

• pain in your right shoulder that radiates to your left shoulder
• shortness of breath
• rapid, strong heart rate (palpitations)
• a feeling of fullness in your chest

Pericardial cysts aren’t dangerous themselves. However, if they press on your lungs or other structures in your chest, they can cause complications like inflammation or severe bleeding. Rarely, a pericardial cyst can lead to heart failure.

A few other conditions and complications can also affect the pericardium.

Pericarditis

Pericarditis is swelling of the pericardium. Possible causes include:

• infection with a virus, bacteria, or fungus
• autoimmune disorders such as lupus, rheumatoid arthritis, and scleroderma
• heart attack
• heart surgery
• injuries, such as from a car accident
• kidney failure
• tuberculosis
• medications such as phenytoin (Dilantin), warfarin (Coumadin), and procainamide

Acute pericarditis starts suddenly and lasts only a few weeks. Chronic pericarditis develops more slowly and can last longer.

Usually pericarditis is mild and heals over time. Sometimes it will improve with plenty of rest. More severe pericarditis may need to be treated with medication or surgery to prevent it from damaging your heart.

Cardiac tamponade

Cardiac tamponade is a condition that’s caused by a buildup of fluid, blood, gas, or a tumor in your pericardial cavity. This buildup places pressure on your heart, which prevents it from filling and emptying properly.

Cardiac tamponade is not the same as pericardial effusion, though it can be a complication of fluid buildup from pericardial effusion.

One sign of cardiac tamponade is a large drop in blood pressure. Cardiac tamponade is a medical emergency. It can be life threatening if it isn’t treated quickly.

The pericardium anchors and protects your heart and allows it to move easily within your chest. When fluid or other substances build up in the pericardium, they can put pressure on your heart and affect its ability to pump blood.

Some conditions that affect the pericardium aren’t serious and will improve on their own. Others can damage your heart and are considered medical emergencies.

If you have symptoms such as chest pain, shortness of breath, and a feeling of fullness in your chest, see your doctor right away. They can perform tests to find the cause of the problem and advise you about treatments to prevent heart damage.

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On the question of the histogenesis of cardiac myxoma

Attempts to determine the biological nature and sources of growth of cardiac myxoma (MC) were made by many researchers throughout the entire period of its study. And if the neoplastic nature of MS is not in doubt by now, then the sources of growth of this tumor still remain unclear and require further clarification and embryological correspondence.

Immunohistochemical and ultrastructural studies revealed signs of endothelial, smooth muscle cells, cardiomyocytes and fibroblasts in MS. Taking into account the localization of MS and the nature of their connection with the endocardium, supporters of the pluripotent concept believe that the source of tumor growth is undifferentiated pluripotent (reserve, cambial, stem) cells, endocardial or subendocardial cells, which are probably capable of differentiating into several mature cell types – fibroblast, endothelial, smooth muscle and myocardial cells [1–4]. Some researchers allow cartilaginous, epithelial, and even neuroendocrine differentiation of myxoma cells [5].

There is another point of view, the proponents of which believe that immature pluripotent subendocardial cells, being the source of MS growth, differentiate only in one direction, towards the vascular endothelium [6–10]. At the same time, some authors [11, 12] assumed the formation of vessels of the fetal type in MS and assumed its hamartomatous origin. Due to the lack of clear ideas about the sources of growth, MS is classified in the International Classification of 2004 as benign tumors from the pluripotent mesenchyme [13].

The purpose of this work is to study the morphological and phenotypic features of MS, search for the sources of its growth, and discuss issues of tumor histogenesis.

Material and methods

Samples of 176 MS (biopsy and autopsy material of patients aged 3.5 to 86 years) obtained from various hospitals in Moscow, including sporadic (162 cases) and family variants (14), were studied. In the chambers of the heart, tumors were located as follows: in the left atrium, 76.1% (of which, in the region of the oval fossa, 57.9%), in the right atrium 17.6% (in the area of ​​the oval fossa 8.8%), the biatral location was detected in 2.3%, in the left ventricle — in 23%, in the right ventricle — 1.7%.

For histological examination, tissue samples were fixed in 10% neutral formalin or Carnoy’s fluid, embedded in paraffin. Sections 5 µm thick were stained with hematoxylin and eosin, picrofuchsin, resorcinol fuchsin, toluidine blue, and alcian blue. The PAS reaction, the reactions of Brachet, Feulgen, Perls, von Koss, and the azocarmine method of Heidenhain were used. Lipids were detected using Sudan III.

For electron microscopy, 54 MS samples were examined from various sites, including the tumor pedicle. The material was fixed in 2.5% glutaraldehyde and 1% buffered osmium tetroxide, dehydrated, and embedded in a mixture of epon and araldite. Ultrathin sections were counterstained with uranyl acetate and lead citrate and examined under JEM-100B and JEM-100C electron microscopes. Semi-thin sections after resin removal were stained with Harris’ hematoxylin and eosin, methylene blue and azure II.

Immunohistochemical studies were carried out in 37 samples of M.S. Paraffin blocks were used (after formalin fixation), from which sections were previously obtained for histological studies. We studied various parts of the tumors, including their surface and legs. Serial sections 4–5 µm thick were deparaffinized according to the standard scheme. Studies were performed using mono- and polyclonal antibodies: vimentin (V9, 1:50, DAKO), cytokeratins (AE1/AE3, DAKO), Ki-67 (B 56, 1:10, BD Bioscienses), α-fetoprotein -Re (2B 8, 1:250, DAKO), type IV collagen (CIY 22.1, DAKO), von Willebrand factor (rabbit, DAKO), VEGF (sc-7269b 1:100, Santa Crus), CD-31 (JC/70A, 1:40, DAKO), α-actin (a-SM-1, 1:250, Novocastra). When using antibodies to CD-31, Ki-67, broad-spectrum cytokeratins, and vascular endothelial growth factor, sections were pretreated in microwave mode (MW-processing). To increase the sensitivity of the method and enhance specific staining, sections with applied primary antibodies were incubated for 20 min at room temperature, then 18 h at 4°C. When using antibodies to type IV collagen and factor VIII, the sections were pretreated with a trypsin solution (SIGMA) for 30 min at room temperature. A standard KIT (DAKO Strept AB Complex/HRP Duet, Mouse/Rabbit) was used as secondary biotinized antibodies of the avidin–horseradish peroxidase system. Diaminobenzidine solution DAB 9 was used as a developing system.0077 + (DAKO). The nuclei were then stained with Mayer’s hematoxylin. The intensity of the peroxidase label was assessed by a semi-quantitative method (weak staining +, moderate ++, intense +++). The proliferative activity index of myxoma cells (Ki-67) was calculated as the average value of cells whose nuclei were stained with the marker per 100 tumor cells. At the same time, at least 500 cells were counted in each preparation.

Results

Sporadic MS did not differ in their morphological characteristics from familial tumors and had a homogeneous histological picture (in the absence of inflammatory changes). In the loose myxomatous matrix, few oval or elongated cells were found, located singly or in small groups. Myxomous cells had light vacuolated cytoplasm. Due to pronounced vacuolization, tumor cells sometimes acquired a pseudo-process or stellate appearance. Oval monomorphic nuclei were characterized by moderate hyperchromia. Mitoses were not found in them. Myxoma cells largely resembled endotheliocytes (Fig. 1, a, Fig. 1. Histological characteristics of cardiac myxoma. a — typical structure of cardiac myxoma, ×200; b — surface of cardiac myxoma is lined with cells that make up tumor tissue, ×200; c — wide tubular embryonic-type vessels in the myxoma of the heart, ×160; d — vessels in the tumor, represented only by myxoma cells, ×240; e — vessel in the tumor, represented only by myxoma cells, the surrounding matrix is ​​rich in glycosaminoglycans, ×400; f — vessel represented by only myxoma cells, basement membrane is not detected, ×400 g — fragment of a large vessel, represented only by myxoma cells, ×400 h — accumulation of acid glycosaminoglycans around myxoma cells Stained with toluidine blue, ×400 a—g — stained with hematoxylin and eosin b). Small groups of compactly arranged cells formed vascular fissures and wide tubular structures resembling embryonic protocapillaries (see Fig. 1c, d). Large vessels in the tumor were formed by only a few layers of myxoma cells. The basement membrane, smooth muscle and adventitial membranes were not found in them (see Fig. 1, e, g). In the myxomatous matrix and, mainly, around the myxoma cells and the primitive vessels formed by them, a wide layer of the basophilic matrix, represented by acidic glycosaminoglycans and glycoproteins, was constantly detected (see Fig. 1h). The accumulation of these substances in the intercellular matrix gives MS a characteristic consistency that determined the name of the tumor. The structural features of myxoma vessels determined their slight vulnerability during traction in the turbulent blood flow of the contracting chambers of the heart. Around the myxoma vessels containing erythrocytes, regardless of the diameter of their lumen, diapedetic and focal hemorrhages, hemosiderin deposits were constantly detected.

It should be noted the structural features of the tumor stem, part of which contained the structures of the original mature endocardium with the presence of connective tissue fibers and mature vessels. Such vessels, located closer to the base of the tumor and in the adjacent sclerosed endocardium, had a closing type of structure with narrow lumens. MS do not have capsules. Their surface is lined with a thin layer of myxoma (endothelial-like) cells similar to those found in the tumor tissue and its vessels (see Fig. 1b). During inflammation, masses of fibrin are deposited on the surface of the tumor. Organized fibrin formed a false capsule and mimicked multifocal tumor attachment to the parietal or valvular endocardium. Inflammatory changes in MS are a very common condition. In this case, the tumor tissue acquires an uneven density and contains inflammatory infiltrates of varying intensity, prevalence and maturity. In MS, hematogenous elements, areas of connective tissue, siderofibrous nodules, foci of cartilaginous and bone metaplasia, and lime deposits can be detected.

Electron microscopic examination of MS tissue revealed a number of features of the ultrastructure of this tumor. Low proliferative activity of myxoma cells was noted: shallow invaginations of the nuclear surface, chromatin condensation at the inner leaf of the karyolemma, eccentric arrangement of nucleoli, and the absence of mitotic figures. Rare small oval mitochondria with few cristae indicated a low energy supply of metabolic processes in these cells. The morphological immaturity of myxoma cells was characterized by the absence of any well-defined structures in their cytoplasm that determined the specific function of differentiated cells; microtubules were not identified; free ribosomes did not form polygonal structures. Microfilaments are unevenly distributed and randomly located. Intermediate filaments are single, thin, short, without clear tissue differentiation. The Golgi apparatus is not developed and is represented only by a few flattened cisterns and single sacs. The transport function is performed mainly by dilated tubules of the smooth endoplasmic reticulum. These ultrastructural characteristics did not allow identifying myxoma cells with any of the mature cell types (fibroblasts, smooth muscle cells, and endotheliocytes).

An important feature of myxoma cells was their ability to synthesize glycoproteins and acidic glycosaminoglycans characterized by high electron density, which is not characteristic of the definitive cells of the noted mesenchyme derivatives (Fig. 2, a, Fig. 2. Ultrastructural characteristic of the myxoma of the heart. a — secretory electron-dense granules in in the cytoplasm of myxoma cells, the matrix surrounding the cell does not contain fibrillar structures, × 5000 b — large secretory granules near the luminal surface of the myxoma cell, × 15 000 c — formation of the vascular cavity by myxoma cells Micropinocytic vesicles, cytoplasmic processes, slit-like junctions and desmosomes. fibrillar structures are not detected in the perifocal flocculent matrix, ×5000 d — interdigitations, slit-like junctions and desmosomes Micropinocytic vesicles near the luminal surface of cells, ×5000 e — multiple finger-like protrusions of neighboring cells, ×25000; f — slit-like junctions and desmosomes between adjacent cells myxoma cells, ×10,000 b). Upon completion of exocytosis, the emptied cisterns of the endoplasmic reticulum created not only an ultrastructural, but also a histological picture of vacuolization, multi-layered or stellate cells. Condensation of these substances in the form of flocculent material around single cells, vascular-like slit-like structures or in their lumen was noted. The secretion of such substances is characteristic of a number of closely related derivatives of the mesenchyme at the early stages of their differentiation, including immature endotheliocytes. The secretion of glycosaminoglycans and glycoproteins in myxoma cells is directed, probably, to the construction of the basal layer. At the same time, myxoma cells did not synthesize any fibrillar structures and were not found around them.

Further ultrastructural analysis revealed signs of incomplete endothelial differentiation in myxoma cells, primarily features of vasoformation and features of intercellular contacts: narrow spaces with the formation of finger-like protrusions, interdigitations, simple and complex gap junctions, desmosomes were detected in neighboring closely spaced cells (see Fig. 2c, f). Similar intercellular contacts of the lateral surfaces of mature endotheliocytes, but expressed to a greater extent, are a characteristic feature that unites individual cells into a tissue. The signs of endothelial differentiation of myxoma cells also include the formation of micropinocytic vesicles that appear near the luminal surface of the cytolemma (see Fig. 2c, d).

To clarify the tissue affiliation of myxoma cells, immunohistochemical studies were performed using specific antibodies. The results obtained are shown in the table. Results of immunohistochemical studies

Oncofetal protein α-fetoprotein is an analogue of adult albumin. It is considered a universal tumor marker and is used to diagnose malignant neoplasms. It is not expressed on the receptors of benign tumors. At the same time, α-fetoprotein receptors are expressed on the membranes of not only proliferating, but also all embryonic cells. In our observations, the total intense reaction of myxoma cells with antibodies to α-fetoprotein receptors was evaluated as evidence of the embryonic status of MS cells (Fig. 3a). Rice. 3. Immunohistochemical characterization of cardiac myxoma. a — expression of receptor α-fetoprotein by myxoma cells, ×200; b — expression of vimentin by myxoma cells, ×200; c — expression of CD-31 by myxoma cells, ×400; d — expression of factor VIII by myxoma cells, ×200; e — lack of expression of type IV collagen in the myxoma vessel, ×400; f — lack of expression of type IV collagen in myxoma cells forming the vessel, ×400; g — no expression of A1/A3 cytokeratins by myxoma cells, ×160; h — lack of expression of smooth muscle actin by myxoma cells, ×100. The mesenchymal origin of myxoma cells was shown with the help of vimentin, a positive reaction with which was intense in all observations (see Fig. 3b). Expression of the endothelial CD-31 marker was noted in all cases. Myxoma cells with intense staining amounted to 56% (see Fig. 3c). Expression of factor VIII, which is also a specific marker of endothelial cells, was detected in all cases (see Fig. 3d). At the same time, moderate and intense staining was noted only in the vascular structures formed by myxoma cells. Vascular endothelial growth factor (VEGF) was detected in our observations both in vascular structures and in separately located cells. However, the expression intensity of this factor was uneven, ranging from moderate to weak, and was observed in 66–88% of cells.

The results of the reaction with a specific marker of type IV collagen involved in the construction of the basement membrane of blood vessels turned out to be of fundamental importance. In all our observations, a negative result was obtained (see Fig. 3, e, f).

The results of immunohistochemical reactions with cytokeratins A1/A3 and smooth muscle actin turned out to be very significant. In all observations, a negative result of these reactions was revealed (see Fig. 3, g, h).

Discussion

The results of histological, ultrastructural and immunohistochemical studies made it possible to compare myxoma vessels with embryonic protocapillaries, and myxoma cells with primordial endothelium or protocapillary endothelium, which form the walls of the primary vascular network, which persists in humans during the period from 4 to 8 weeks of embryonic development. The same period coincides with the formation of the human heart, and the formation of the endocardium begins with the fusion of endothelial tubes represented by protocapillaries. The noted characteristics of myxoma cells, their ability to synthesize glycoproteins and acidic glycosaminoglycans, and the tendency to vasoformation coincide with the characteristics of the embryonic endothelium. Myxomal vessels, like the embryonic protocapillaries of the germinal mesenchyme, do not have a basement membrane. According to V.V. Kupriyanova et al. [14], the basement membrane around the vessels appears later in ontogeny, only during the formation of the secondary capillary bed. Large functioning myxoma vessels are represented by one or several layers of myxoma cells surrounded by condensed masses of acidic glycosaminoglycans and glycoproteins. Smooth muscle and adventitial membranes in myxoma vessels were also absent. Some assumptions about the origin of myxoma cells from the embryonic endothelium of the endocardium were reflected in our previous studies [15, 16].

Some molecular-biological (biochemical, but not structural) markers identified by a number of researchers, characteristic of fibroblasts, cardiomyocytes, and/or smooth muscle cells, only confirm our embryological ideas about the cross-properties of immature, closely related mesenchyme derivatives that still retain the features of their predecessors. This hypothesis is largely consistent with the results of genetic and molecular biological analysis carried out by A. Di Vito et al. [17].

Taking into account the noted features of MS, the cells and vessels of which correspond to embryonic structures that have not reached their final differentiation in the postnatal period, it can be assumed that the source of their growth is a tissue malformation of the embryonic endothelium of the parietal endocardium — tissue monohistioid hamartia [18]. The formation of such hamartia during the formation of the heart can be due to any damaging factor. Violation of the processes of maturation of the embryonic endothelium and its incompleteness in one or another area of ​​the parietal endocardium lead to long-term persistence (hamartia), including the postnatal period.

There are other variants of embryonic endothelial hamartia, in particular hamartia of the valvular endocardium. These include Lamble’s excretions, the giant variants of which are considered papillary fibroelastomas, Albini’s nodules and their sclerosed analogues of Arantia’s nodules, as well as myxomatosis (dysplasia) of the heart valves, including additional ones.

Embryonic hamartia tend to proliferate [18]. Proliferation of the persistent embryonic endothelium (delayed in its differentiation) of the parietal endocardium can lead to the formation of a benign hamartoma tumor. Such a hamartoma, a disembryogenetic benign tumor, is MS.

Hamartomas are usually detected in the postnatal period – childhood, adolescence or adulthood. Hamartias and tumors from them, hamartomas, can be familial, transmitted in an autosomal dominant pattern of inheritance, and accompanied by other developmental anomalies known as hamartomatous syndrome. Such, for example, are the Peutz-Jeghers-Tourene syndrome or the Bourneville syndrome. This fully applies to M.S. Myxomas of the heart are also transmitted in an autosomal dominant pattern of inheritance. According to our data, MS in 7.7% of cases had a familial character and was accompanied by hamartomatous syndrome (myxoma syndrome, SWISS syndrome, NAME syndrome, Karney syndrome). In our observations, myxoma syndrome was noted in 23.4% of cases, and its monosymptomatic variant — in 43.3%.

Conclusion

The results of our study give grounds to speak in favor of the hypothesis that the histogenesis of myxoma of the heart can be considered from the standpoint of a benign dysontogenetic tumor of hamartoma. The immature (embryonic) endothelium, monohistioid hamartia, can serve as a source for the development of myxoma of the heart. In essence, myxoma of the heart is an embryonic endothelioma of the endocardium. The results of our studies do not exclude the possibility of the origin of cardiac myxoma from a pluripotent mesenchymal source.

Author contributions:

Study concept and design — K.