High altitude heart disease

Introduction to high altitude heart disease High altitude heart disease refers to normal people who migrate to the plateau from low altitudes or live in the plateau for a long time. Due to chronic hypoxia, pulmonary vasoconstriction, thickening of the wall muscle layer, increased pulmonary circulation resistance, pulmonary hypertension and myocardial deficiency Oxygen, a heart disease that eventually leads to right ventricular hypertrophy and heart failure. basic knowledge The proportion of illness: 0.001%-0.003% Susceptible people: no specific population Mode of infection: non-infectious Complications: high blood pressure

Causes of high altitude heart disease

Causes:

Plateau heart disease occurs mostly in the plains who migrate to the plateau or from moderate to higher altitudes. The incidence increases with altitude. Hypoxia is the causative factor of this disease. Hypoxic pulmonary hypertension It is the main manifestation of this disease. Plateau hypoxia causes erythrocytosis, increased blood viscosity, increased total blood volume and pulmonary blood volume, and direct damage to the myocardium by hypoxia. Cold, smoking, overwork, and upper respiratory tract infections are predisposing factors for this disease.

Pathogenesis:

Hypertensive disease is mainly caused by chronic hypoxia caused by impaired right heart function, whether the left ventricle is also affected, or how the degree of involvement is unclear. Hypobaric hypoxia is the root of high-grade heart disease, and hypoxic pulmonary hypertension and pulmonary arteriolar wall The thickening or remodeling is the central link or basic feature of the pathogenesis.

1. Pulmonary hypertension was studied by clinical and animal models. The pulmonary arterial pressure of chronic high altitude disease, especially high heart disease, was abnormally elevated. Hultgren reported 16 cases of Monge disease hemodynamic changes in Peru (4206m), with an average pulmonary artery pressure of 44.47. mmHg, the average pulmonary vascular resistance is 531sce-cm2; Yang et al reported in Qinghai (3950m) that the average pulmonary artery pressure of mixed chronic high altitude disease is 30.7mmHg, long-term persistent hypoxic pulmonary vasoconstriction and pulmonary hypertension, making the right heart The post-load gradually worsens and the right ventricular compensatory hypertrophy occurs. When the disease course continues to develop, the reserve capacity of the heart further decreases. At the same time, hypoxia can damage the myocardial cells, weaken the contractility of the heart muscle, reduce the cardiac output, and eventually lead to right heart failure. Regarding the mechanism of hypoxic pulmonary vasoconstriction, although many studies have been carried out, the exact mechanism is still unclear. The current accepted view is:

(1) The role of vasoactive substances: The lung has a unique role in the regulation and regulation of vasoactive substances. Pulmonary vascular endothelial cells are important sites for the secretion and synthesis of vasoactive substances, and can synthesize and release two types of vasopressors. Substance, which plays an important role in regulating vascular tone. The most important aspects of diastolic blood vessels are prostaglandin (PG) and nitric oxide (NO), also known as endothelium relaxing factor (EDRF); Endothelin (ET) and angiotensin II (angiiotensin II) are involved in contracting blood vessels.

PG is widely distributed in various tissues and body fluids of mammals, and its lung tissue is the highest. Prostaglandins are converted into PGE2, PGF2, PGD2, PGI2 and thromboxane A2 by the action of prostacyclin syhthetase (PGI3). TXA2), TXB2, etc., PG's physiological function is very complex, can participate in a variety of tissues and organs physiological and biochemical processes, but its role is selective, PG and its precursors, intermediates and metabolites have very much on the pulmonary blood vessels Strong relaxation effect, in which PGI2 and TXA2 maintain balance in the blood plays an important role in the regulation of pulmonary circulation. PGI2 is synthesized by vascular endothelial cells and smooth muscle cells, which has diastolic pulmonary vasculature, reduces vascular resistance, and inhibits proliferation of smooth muscle cells. While TXA2 is synthesized by platelets, its effect is opposite to that of PGI2. Studies have confirmed that hypoxia causes a decrease in the level of 6-keto-PGF1 (oxide of PGF1) in the blood, while TXB2 (degradation product of TXA2) increases, and Li Ruirui measures The levels of plasma 6-keto-PGF1 and TXB2 in healthy people in plains and highlands were found to be significantly increased in the plateau group 6-ketone PGF1, while TXB2 was decreased, T/P ratio increased, 2 times higher than plain people. It is suggested that plateau hypoxia may damage pulmonary vascular endothelial cells, which reduces the synthesis of PGI2 and increases the release of TXA2. Recently, Geraci (1999) and other genes that use the specific surfactant apolipoprotein-C to transcribe mice, ie transgene (Tg+) And non-transgenic (Tg-) mice, exposed to simulated 5180m elevation for 5 weeks, found that Tg + murine plasma 6-keto PGF1 content was twice as high as Tg-mouse, and pulmonary arterial pressure was normal, no morphological changes, In Tg-mouse, pulmonary hypertension and pulmonary vascular wall thickening indicate that transgene can increase PGIS cDNA synthesis, increase blood PGI2 content, resist hypoxic pulmonary vasoconstriction and inhibit smooth muscle cell proliferation, and prevent hypoxic pulmonary artery. High-pressure and pulmonary vascular reconstruction, recently, PGIS transgenic therapy for primary pulmonary hypertension and other vascular diseases has achieved good results.

ET is synthesized and secreted by vascular endothelial cells. There are three kinds of ET in human body, namely ET-1, ET-2 and ET-3. Among them, ET-1 is recognized as the strongest pulmonary vasoconstrictor, a polypeptide consisting of 21 amino acids. Modern studies have shown that both acute and chronic hypoxia can stimulate endothelial cell synthesis and release ET, which causes the pulmonary blood vessels to contract strongly. The increase of plasma ET-1 concentration is related to the degree of tissue hypoxia. Goerre et al. When the plateau reached 4559 m, the plasma ET-1 concentration was twice as high as that of the plain, and the increase of ET-1 was negatively correlated with PaO2 (r=-0.45, P<0.01), but positively correlated with pulmonary artery pressure (r=0.52, P < 0.02), it was reported that plasma ET-1 concentration peaked when exposed to 10% oxygen for 10 min, and peaked within 10 min of exposure to 5% oxygen. In addition to ET-1 increase in hypoxia In addition, plasma atrial natriuretic factor (ANF) and arginine vasopressin (AVP) levels were also significantly increased, suggesting that these peptides have very different physiological effects, but regulate There is an inherent interrelationship in the pulmonary circulation. Some people think that AVP can stimulate blood. Endothelial cells secrete ET-1; while the increase of ET-1 in plasma can promote pulmonary vasoconstriction, pulmonary hypertension and right atrial involvement, which causes ANP secretion and release, so ET-1 is one of the factors released by ANP, plateau Residents, especially those with high redness, have a significant increase in ANP. ANP can dilate blood vessels, reduce venous return, and prevent pulmonary hypertension. Under chronic hypoxia, ET-1 can promote pulmonary arteriolar smooth muscle hypertrophy and thus further Increased pulmonary artery pressure, in addition, the level of angiotensin-converting enzyme (ACE) in patients with high altitude pulmonary edema and hyperredness is 3-4 times higher than that of normal people in the high altitude, indicating that acute and chronic hypoxia can promote pulmonary vascular endothelial cell synthesis. ACE, and accelerate the conversion of angiotensin I to angiotensin II and degrade vasodilators to cause pulmonary vasoconstriction.

(2) Cell membrane ion channel function: It is known that the change of cell membrane ion permeability and the resulting ion transmembrane potential play an important role in pulmonary vasomotor, and the level of blood oxygen partial pressure in the body can regulate the ion channel. Activity; changes in ions have different effects on pulmonary vessels. For example, an increase in intracellular K+ concentration can relax blood vessels; while an increase in Ca2 concentration can contract blood vessels, and extracellular K+ and Ca2 have competitive inhibition on smooth muscle cell membrane; hypoxia It can inhibit K+ influx of pulmonary artery smooth muscle cell membrane, depolarization of cell membrane resting potential and acceleration of Ca2 flow, resulting in increased intracellular free Ca2 concentration, which promotes pulmonary vascular smooth muscle contraction, increased pulmonary artery pressure, and calcium antagonist that inhibits Ca2 influx ( Verapamil can effectively treat pulmonary hypertension, indicating that Ca2 has a certain relationship with the occurrence of pulmonary hypertension.

2. Pulmonary vascular structural reconstruction Animal experiments and clinical data confirmed that long-term severe hypoxia caused morphological changes in pulmonary vasculature, which was mainly characterized by the thickening of the pulmonary arterioles and the muscles of small arteries (diameter <100 m) without smooth muscle. Hypoxic vasoconstriction is the initial mechanism leading to pulmonary arteriosus; thickening of the muscular layer can further promote the increase of resistance of pulmonary arterioles, increase contractility, and increase pulmonary artery pressure. Li et al found in autopsy of high heart disease. The pulmonary arteriolar wall is obviously thickened, especially the middle smooth muscle is increased, and the thickness of the blood vessel wall is increased as a percentage of the outer diameter of the blood vessel. In addition, the pulmonary vascular endothelial cells are swollen, protruding circularly to the lumen, or vertically aligned with the tube wall. It has been found that the thickness of the pulmonary arterioles of the rats that migrated to the plateau accounted for 27.2% of the outer diameter of the blood vessels, while the native plateau pikas only accounted for 9.2%, and the thickening of the vessel wall was positively correlated with the mean pressure of the pulmonary arteries (r=0.769). Reconstruction of pulmonary vasculature often occurs in primary pulmonary hypertension, chronic cardiopulmonary disease, etc., but morphological changes differ in some respects from hypercardiac disease caused by hypoxia alone, such as pulmonary vessels. The thickening is mainly caused by intimal proliferation and adventitial fibrosis. Pulmonary vascular remodeling caused by chronic alveolar hypoxia is mainly manifested in the proliferation or migration of vascular smooth muscle cells, but There are different opinions and theories about its mechanism. It is known that the relaxation of the arterial ring of acetylcholine depends on the integrity of the vascular endothelium, indicating that there is a close relationship between endothelial cells and adjacent smooth muscle. It is believed that hypoxia can directly damage endothelial cells. Reduce the synthesis of endogenous vasodilators (PGI2, NO, etc.) and release certain growth factors to promote vascular smooth muscle cell proliferation and hypertrophy, including ET-1, ACE, platelet derived growth factor (PDGF), Insulin-like growth factor (IGF), etc., growth factors are polypeptide glycoproteins that are synthesized and released by specific cells and signaled to adjacent cells for replication or phenotype ( Phenotype) changes, their main function is to change the cells through cell chemotaxis, division, phagocytosis and degradation. As such as a skeletal arrangement of cells, cell shape and shrinkage, thereby producing cells proliferation and extracellular matrix proteins and the like, pulmonary vascular remodeling now associated with the growth factor directly to a brief introduction.

(1) VEGF can be synthesized by alveolar macrophages, vascular smooth muscle cells and endothelial cells. It has two specific receptors, Flk-1 and Flt-1, which are present in endothelial cells. The activity of VEGF depends on HlF- 1, chronic hypoxia increased the synthesis of HlF-l, which in turn promoted VEGF gene transcription, accelerated VEGF synthesis and release, the author used immunohistochemical staining, pulmonary artery arteriolar smooth muscle cells VEGF-Flt positive, and blood vessels The thicker the wall, the stronger the immune response. Tuder and Christon found that in the animal model of chronic hypoxic pulmonary hypertension, the VEGF-Flk receptor mRNA was significantly increased, and the VEGF-Flt-1 in the smooth muscle cells of the pulmonary arterioles was strong. Positive, suggesting that VEGF can participate in the process of hypoxic pulmonary revascularization.

(2) Transforming growth factor-1 (TGF-1): is a multifunctional growth factor. There are three types of TGF: TGF-1, TGF-2 and TGF-3; TGF-1 is a dimerization with molecular weight of 25KD. Body, it exists in various tissues such as platelets and lungs; it has strong proliferation and fibrosis effects on pulmonary vascular smooth muscle, endothelium and interstitial lung, and migrates to the pulmonary arterioles and bronchioles of plateau rats. Monocytes, macrophages and neutrophils were strongly positive against TGF-1 antibody, but no such reaction was found in plateau pikas. In addition, pulmonary vascular smooth muscle cells in patients with primary pulmonary hypertension and pulmonary heart disease were associated with TGF. -1 also appears positive, TGF-1 may be secreted by a variety of cells, such as mast cells, endothelial cells, neutrophils and alveolar macrophages, etc., its activity depends on the presence of other cytokines.

(3) Mast cell tryptase: Early studies confirmed that the density of mast cells around the perivascular vessels of rats inhaled with hypoxic gas increased and degranulation appeared. It is believed that mast cells release certain media such as group. Amine and other pulmonary vasoconstriction, along with the development of immunohistochemistry and molecular bioassay techniques, found that mast cells, in addition to releasing vasomotor mediators, also synthesize and release many growth factors, of which Tryptase and chymase (chymase) are At present, the familiar polypeptide growth factor secreted by mast cells, Tryptase was first purified from human lung tissue mast cells in 1981, and its molecular weight is 110-140KD. It is a large molecular weight complex, asthma patients and smokers. The content of Tryptase in alveolar lavage fluid is extremely high. Recently, cell culture of lung tissue found that Tryptase can stimulate new blood vessel growth, which is considered to be a newly discovered angiogenic factor. Some people used monoclonal antibody immunohistochemical staining and found The tryptase of mast cells around the pulmonary arterioles of the plateau rats was strongly positive, while the plateau pikas were not seen. He positive reaction, also found that lung emphysema and pulmonary heart disease patients with chronic emphysema surgery (Lung-volume reduction surgery) pulmonary vascular, small bronchial and interstitial lung mast cells increased density, Tryptase immune response Positive, the density of mast cells around the pulmonary arterioles was positively correlated with the thickness of the vessel wall (r = 0.87). Heath et al found that there were a large number of small arteries around the plateau in the human lung tissue of Bolivia. Mast cells accumulate and suggest that the effect of mast cells on vascular remodeling seems to be more important than the role of vasoconstrictors.

There are very few pathological reports on autopsy of high heart disease. Only 5 cases are reported in foreign literature. The main features of pathology are increased heart volume and weight; right atrium, right ventricular dilatation hypertrophy, right ventricular weight accounting for 67% of the whole heart (normally 30) %), middle layer thickening of pulmonary arterioles, endometrial fibrosis in some patients, extensive obstructive thrombosis in small and medium pulmonary arteries, hepatic congestion and swelling, domestic Tibetan scholars reported autopsy of 20 adults and 57 children with high heart disease, and found changes in the heart Similar to the foreign report, under the light microscope, the myocardium, especially the right ventricular papillary muscle and the right ventricular wall, have severe muscle fiber degeneration, necrosis, calcium salt deposition and scar formation. Electron microscopy shows myofibril dissolution, destruction, mitochondrial swelling and cavitation. Visible dense particles, endoplasmic reticulum dilatation and reduction of glycogen granules, pulmonary vascular changes, manifested in the middle layer of pulmonary arterioles and small arteries without smooth muscle (diameter <100m) muscle, thickened in addition to the middle smooth muscle Cell proliferation, proliferation of the intima and outer fibrous tissue; some small arterial endothelial cells are swollen, and the lumen of the lumen causes the lumen of the lumen to narrow or even Plug.

Plateau heart disease prevention

prevention:

1. Before entering the plateau, you must do the necessary preparations to prevent factors that may induce high altitude heart disease, especially to control upper respiratory tract infections.

2. Take spironolactone 20mg, 3 times / d or acetazolamide 0.25g, 3 times / d 3 days before entering the plateau, can reduce the incidence of this disease.

3. At the beginning of the plateau, pay attention to rest, prevent overwork, and rest in bed or take oxygen if necessary.

High altitude heart disease complications Complications

Acute high altitude heart disease can progress rapidly with acute left heart failure, followed by right heart failure. Chronic high altitude heart disease can have complications such as hypertension and right heart failure.

Symptoms of high altitude heart disease Common symptoms Difficulty of breathing, loss of appetite, restlessness, nose, fan, right heart failure, shortness of breath, bradycardia, palpitations, lips, palpitations

Symptom

The clinical manifestations of children with adult hypertensive disease are different. The incidence of children is earlier, the disease progresses rapidly, the adult is slow, and the symptoms appear later. The early symptoms of children are irritability, sleepless nights, loss of appetite, cough, and cyanosis. , sweating, followed by apathetic, shortness of breath, rapid heart rate, increased cyanosis, edema, oliguria, digestive tract dysfunction; if there is respiratory infection, the body temperature rises, cough increases, eventually develops right heart failure, adult The onset is slow and the symptoms gradually worsen. In the early stage, only chronic altitude sickness and mild pulmonary hypertension, such as headache, fatigue, sleep disturbance, loss of appetite, etc., with further development of the disease, palpitations, chest tightness, difficulty breathing, neck Intravenous filling, hepatomegaly, lower extremity edema and other manifestations of right ventricular dysfunction.

2. Signs

Pediatric development is generally poor, shortness of breath, nose flapping, lip cyanosis, heart rate increase, heart expansion; most children in the anterior or tricuspid valve area can be heard and II-III systolic hairy murmur, pulmonary artery The second sound is hyperactive or split, and the lungs may have dry and wet voices, which are related to pulmonary infection. When right heart failure occurs, the liver enlarges, the lower extremity edema, the jugular vein engorgement, and the jugular vein regurgitation sign is positive. Patients with severe pulmonary infection often have pulmonary edema. Adults often have signs of compensatory emphysema. Some patients have clubbing, lips, nail bed, and blood pressure are normal. The heart is slightly enlarged, heart rate is increased, and a few The patient has bradycardia, the apex of the apex and the systolic murmur of the second grade, and the individual patient has a diastolic rumbling murmur; the second sound of the pulmonary artery is hyperthyroidism, splitting, and the right heart dysfunction may have hepatomegaly, often tenderness, lower limbs. Edema.

Examination of high altitude heart disease

Laboratory inspection :

1. Blood routine erythrocytosis, generally more than 0.6 × 1012 / L, hemoglobin often exceeds 200g / L, hematocrit is more than 0.60. White blood cells are basically normal.

2. A small amount of protein can appear in urine, and red blood cells can also be seen.

3. Liver function may be impaired in liver function and elevated transaminase.

4. Arterial oxygen saturation decreased to varying degrees, and there were significant differences due to altitude differences. For example, the normal person was 90.27% at 3658m and the adult patient was 84.26%.

Other auxiliary inspections:

1. X-ray examination of X-ray manifestations of high altitude heart disease, mainly pulmonary artery bulge, and some may be aneurysmal-like bulge, pulsation enhanced, right lower pulmonary artery dilatation, central pulmonary artery expansion and peripheral branch suddenly changed Fine, so it is cut off or changes in the roots. The hilar shadow is enlarged, the lung pattern is increased, thickened or reticulated. Heart enlargers accounted for 66.3% to 95%, mainly with right heart, apex upturned or rounded, but also with heart-centered enlargement of the right heart, and few left heart enlargement. Children often have a spherical shape and their pulsation is weakened. The superior vena cava shadow is widened.

2. The main characteristic of ECG is that the electric axis is right-biased, extremely clockwise (V5R/S1), P-wave is high-pointed, and it is lung-type P wave, right ventricular hypertrophy with strain and complete or incomplete right bundle branch conduction. Blocking, only a few cases showed bilateral ventricular hypertrophy. A small number of patients have SI, SII, SIII patterns, reflecting right ventricular hypertrophy, the left axis of the electric axis is rare, a few are left bundle branch block pattern, or the left ventricle is dominant, the ST segment of the precordial lead is down and the T wave is low. Flat, bidirectional and inverted.

3. Echocardiography is mainly a change in pulmonary hypertension and right heart involvement. The commonly used index of pulmonary hypertension is pulmonary valve a wave <2mm; BC slope is increased, it is reported that the plateau heart disease group is (289.10±45.93) mm/s, while the control group is (228.76±49.32) mm/s; RPEP ( Prolonged right ventricular ejection) and increased ratio of RPEI/RVET (right ventricular ejection time). These indicators are more meaningful and support the diagnosis of high altitude heart disease.

4. Cardiac catheterization showed a significant increase in pulmonary artery pressure, and pulmonary hypertension was inversely proportional to the patient's age and proportional to altitude and hypoxia. Therefore, the younger the age, the higher the altitude of the children, the higher the incidence of children.

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Diagnosis and diagnosis of high altitude heart disease

Diagnostic criteria

1. Generally, migrants who are above 3,500 m above sea level are prone to morbidity, and individual seizures who are susceptible to hypoxia may also suffer.

2. The clinical manifestations are mainly pulmonary hypertension, right ventricular hypertrophy and right heart failure, irritability in children, no sleep at night, difficulty breathing, cyanosis, second sound of pulmonary artery, enlargement of the liver, edema of lower limbs, etc. Adults have heart palpitations and fatigue. Inability, cough, difficulty breathing, pulmonary artery second tone hyperthyroidism or division, severe cases of liver enlargement, lower extremity edema, oliguria and so on.

3. X-ray, electrocardiogram, echocardiography, etc. showed signs of significant pulmonary hypertension and right ventricular hypertrophy.

4. Right heart catheterization, the average pulmonary artery pressure > 25mmHg.

5. Exclude other cardiovascular diseases, especially pulmonary heart disease.

6. When the patient moves to the plain or low altitude, the condition is relieved, the pulmonary artery pressure drops, and the heart function returns to normal.

Differential diagnosis

1. Congenital heart disease: The prevalence of congenital heart disease, especially patent ductus arteriosus in high altitude areas is high, and it is easy to be confused with pediatric hypertensive disease, but the systolic murmur of patent ductus arteriosus is rough and conduction, X-ray examination mostly The lung door dance.

2. Pulmonary heart disease: Pulmonary heart disease and high heart disease are very similar in some aspects, there are certain difficulties in identification, but the former has a history of chronic cough, lung ventilation function is significantly abnormal, and the latter's lung function is basically normal.

3. Primary pulmonary hypertension: This disease is rare, the disease progresses progressively, and the disease is not relieved from the plateau environment.

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