RU2117948C1 - Method of diagnosis and myocardium infarction size estimation - Google Patents

Abstract

FIELD: medicine, cardiology. SUBSTANCE: method involves determination of blood sphingomyelin content in patient on the 2-d day of disease. Myocardium infarction is diagnosed at the level of sphingomyelin above 1900 mcmole phosphorus/1 l blood. Infarction myocardium size is determined by the formula: M = 0.054 x C - 99.1 where M - necrosis size expressed as percent of aortic ventricle of heart mass; C - content of blood sphingomyelins (as mcmoles/1 l blood). EFFECT: high precision of assay in one's lifetime. 4 ex, 1 tbl

Description

 The invention relates to medicine and can be used in clinical practice to diagnose myocardial infarction and determine its size by a biochemical method.

 Of the biochemical methods for diagnosing and determining the size of myocardial infarction, the most widely used is the method of a serial study of CPK in blood serum, which implies regular (every 2 or 3 hours) blood sampling from the patient from the moment he enters the hospital to normalize the enzyme content (analogue). The obtained data on the dynamics of the enzyme in the blood allows us to calculate the size of cardiac muscle necrosis, to get an idea of the dynamics of the process, the severity of the disease and the effectiveness of treatment measures. However, the method is not without drawbacks, among which it is necessary to note the need to postpone various therapeutic interventions for 6-7 hours to collect data on the dynamics of CPK in the blood. In addition, the accuracy of the method decreases with extensive myocardial lesions and the localization of a heart attack in the lower wall or septum.

 A known method of biochemical diagnosis of myocardial infarction based on the determination of the level of phosphatidylinositis in the blood. The conclusion about the presence of myocardial infarction is made when the content of phosphoinositides is higher than 880 μmol of phosphorus / l of blood (prototype). The method requires a single blood sampling, is characterized by ease of execution and high diagnostic accuracy (95.5%), but does not provide information about the size of myocardial infarction, which are very important from a clinical point of view.

 The aim of the invention is to improve the accuracy of diagnosis of myocardial infarction and intravital determination of its size.

 The method is as follows.

On the second day of the disease, 0.1 ml of blood is taken from the patient’s finger and placed in a test tube with 3.75 ml of a mixture of chloroform-methanol (1: 2 by volume). Then it is filtered and the filter cake is washed three times with 0.5 ml of a mixture of chloroform-methanol 2: 1. 0.4 ml of 0.02% CaCl _{2 was} added to the filtrate, then stirred for 1-2 minutes. After a clear separation, the upper phase is sucked into the extract three times washed from non-lipid impurities with a mixture of chloroform-methanol - 0.02% CaCl ₂ (3: 48: 47), adding 0.4 ml each, then it is evaporated and dissolved in 5- 10 μl of a mixture of chloroform-methanol 2: 1. After that, the test samples are applied to a chromatographic plate.

Silica gel is applied to the plates by precipitation from dilute aqueous suspensions containing 2.5% salt of K ₂ CO ₃ . Sphingomyelins are isolated by horizontal flow chromatography in a chloroform-methanol-7 n system. ammonia (13: 7: 1). Identification of sphingomyelins is carried out using the values, color tests and witness sphingomyelins firm "Sigma", USA. The quantitative content of the sphingomyelin fraction having Rf = 0.28 is determined by phosphorus, after the chromatograms are manifested by sulfuric acid and calculated in micromoles of sphingomyelin phosphorus per 1 liter of blood.

The conclusion about the presence of a myocardial infarction in a patient is made when the level of sphingomyelins in the blood exceeds 1900 μmol of phosphorus / l. The sizes of necrosis are calculated by the formula:
M = 0.054 • C - 99.1 ± 2.5
Where
M is the size of the necrosis, expressed as a percentage of the mass of the left ventricular myocardium; C is the level of sphingomyelins in the blood in micromoles of phosphorus / l of blood.

 The basis of the proposed method is the data obtained during the examination of 110 patients with coronary heart disease and 50 healthy individuals (control). The average level of sphingomyelins in the control group was 1510 ± 65 μmol of phosphorus / l, in patients with angina pectoris (40 people) - 1788 ± 30, in patients with myocardial infarction - 2050 ± 96 (all p <0.005). Statistical analysis using the non-parametric Fisher test revealed significant (p <0.05) differences in the distribution of patients with various forms of coronary heart disease when using as a boundary value the level of blood sphingomyelins equal to 1900 μmol of phosphorus / l of blood (see table). The accuracy of the diagnosis of myocardial infarction when using the proposed method is 95.7%.

 Correlation analysis showed the presence of a close (r = 0.90, p <0.01) correlation between the level of blood sphingomyelins on the 2-3 day of the disease and the size of the heart attack, determined by the QRS ECG complex assessment system after the tenth day of the disease. Based on the obtained data, a regression equation was derived that allows calculating the size of necrosis based on the level of sphingomyelins in the blood. The average error in determining the size of a heart attack was 2.5%.

In our opinion, the following pathogenetic mechanism is the basis of the dependence of the level of sphingomyelins in the blood on the size of myocardial infarction. The decrease in the propulsive ability of the heart, due to the loss of the contractile ability of the necrotic area of the myocardium, leads to a decrease in blood flow in peripheral tissues, whose oxygen demand is not changed or even increased, due to the activation of the sympathoadrenal system. Under these conditions, tissue oxygen extraction increases and PO _{2 of} venous blood decreases. Blood as a tissue itself appears under hypoxia conditions, which leads to impaired glucose utilization by its cellular elements and, therefore, to block the formation of ceramide from the amino alcohol sphingosine. In this case, due to the activation of specific transferases, an increased amount of sphingomyelin, which serves as a hyperlipogenetic source of energy depot, can form.

 Thus, the level of venous blood oligomyelin reflects, in our opinion, hemocirculatory disorders, the severity of which, in turn, depends on the size of myocardial infarction.

 Clinical examples.

 1. Patient T-s D.A., 64 years old. The medical history N 2291. He is being treated in the cardiology department of the emergency hospital in Tver from 03/31/91 to 05/05/91 with a diagnosis of IHD. Common transmural antero-lateral myocardial infarction.

 He was hospitalized with complaints of intense breaking chest pains that appeared 1.5 to 2 hours before admission to the hospital. He took several tablets of nitroglycerin, which worsened the condition: there was a sharp weakness, profuse cold sweat, suffocation.

 A history of bouts of sternal pain during a year during brisk walking. I did not seek medical help.

 The condition at admission is serious. Acrocyanosis, orthopnosis, shortness of breath up to 30 in 1 min. Rigid breathing in the lungs, wheezing is not heard. Heart sounds are muffled, arrhythmic due to frequent extrasystoles. Heart rate 102 in 1 min; pulse 76 in 1 min; blood pressure 90/60 mmHg. Art. The abdomen is soft, the liver and spleen are not enlarged.

 On the ECG, sinus tachycardia, frequent ventricular extrasystole, sometimes group. Damage zone in the anterior-lateral wall of the left ventricle.

In blood tests: Hb 132 g / l, red blood cells 3.6 • 10 ¹² / l, white blood cells 8.1 • 10 ⁹ / l, white blood cell count unchanged, ESR 8 mm / h, AST 2.1 mmol / l, ALT 1.96 mmol / L (the norm for AST and ALT is 0.06-0.4 mmol / L).

 During the first days of the disease, ventricular fibrillation developed 6 times, interrupted by electrical defibrillation, increased manifestations of left ventricular failure.

 The level of sphingomyelins in the blood on the second day of the disease was 2374 μmol of phosphorus / l, which, along with other clinical and laboratory data, confirmed the diagnosis of myocardial infarction and made it possible to estimate its size in 29.1% of the mass of the left ventricular myocardium.

 During the first week of the disease, the patient's condition remained severe: various rhythm disturbances up to ventricular tachycardia were noted, manifestations of heart failure were expressed. By the end of the first week, the condition stabilized and gradually began to improve.

 On the tenth day of the disease, an ECG analysis was performed to determine the size of necrosis, which amounted to 27.5% of the mass of the left ventricular myocardium.

 The further course of the disease without complications. Discharged on the 34th day of the disease in satisfactory condition.

 2. Patient R-th MA, 56 years old. The medical history N 287. He was treated in the cardiology department of the emergency hospital in Tver from 01/12/92 to 02/05/92 with a diagnosis of IHD. Progressive angina pectoris. A protracted attack with the formation of foci of myocardial dystrophy. Postinfarction cardiosclerosis in the anterior-lateral wall of the left ventricle.

 An SMP was hospitalized with complaints of pressing chest pains arising from the slightest physical exertion.

 In 1989, he suffered an extensive transmural antero-lateral infarction. Since then, he has been hospitalized many times with the clinical picture of progressive angina pectoris. This deterioration over three days: there was a sharp decrease in exercise tolerance, the appearance of chest pains at rest, a decrease in the effect of taking nitroglycerin. The reason for the call for emergency help was an attack of chest pain, lasting more than an hour.

 Condition upon receipt of moderate severity. The skin is warm, dry, moderate acrodianosis. NPV 12 in 1 min, vesicular breathing, inconstant crepitating rales in the lower parts of the lungs. The tones are muffled, rhythmic, heart rate 96 in 1 min, blood pressure 110/80 mm RT. Art. Liver on the edge of the costal arch.

On the ECG, the sinus rhythm, focal changes in the anterolateral wall: Q wave from V ₁ to V ₅ , ST segment elevation to 1.5-2 mm in the same leads.

In blood tests: Hb 144 g / l, red blood cells 4.5 • 10 ¹² / l, white blood cells 6.6 • 10 ⁹ / l, formula unchanged, ESR 12 mm / h, AST 0.74 mmol / l, ALT 0 66 mmol / L. The level of blood sphingomyelins on the second day of the disease is 1880 μmol of phosphorus / l.

 On admission, a diagnosis of acute myocardial infarction was made, but on the basis of a set of instrumental and laboratory studies, this diagnosis was removed.

 During his stay in the hospital, the patient's condition improved significantly. Discharged with a clinic of stable angina of exertion of the 2nd functional class.

 3. Patient And. A.A., 54 years old. Case history 1903. He was treated in the cardiology department of the Tver Emergency Hospital from 03/13/92 to 04/11/92 with a diagnosis of CHD. Large-focal non-penetrating myocardial infarction of the lower wall of the left ventricle.

 Hospitalized in the direction of the local doctor; no complaints at admission.

 Two days before admission to the hospital, for the first time in my life there were burning chest pains radiating to the left hand. The pain persisted for more than an hour, gradually subsided. On this day, the patient did not seek medical help, but the next day he called the local doctor at home. A sick leave was issued, an ECG study was prescribed. After registering the ECG, the patient was sent to a hospital.

 Condition at admission is satisfactory. The skin is of normal color. In the lungs, vesicular breathing. Heart sounds are muffled, rhythmic, heart rate 72 in 1 min, blood pressure 120/70 mm RT. Art. The abdomen is painful, the liver and spleen are not palpable.

 On admission ECG: sinus rhythm, correct direction of the electrical axis of the heart. Pathological Q wave in II, III and VI leads. In the same leads, the ST rise is 1-1.5 mm, the inversion of the T wave.

In blood tests: Hb 144 g / l, red blood cells 4.6 • 10 ¹² / l, white blood cells 6.5 • 10 ⁹ / l, the formula is not changed, ESR 18 mm / h, AST 0.55 mmol / l, AL 0 4 mmol / l.

 The level of blood sphingomyelins on the day of admission (the third day of the disease) is 1980 μmol / L, the estimated mass of necrosis is 7.8%. The sizes of necrosis, estimated by ECG on the tenth day of the disease, amounted to 5% of the mass of the left ventricular myocardium.

4. Patient K. s. F. F., 63 years. Case history No. 1715. He was treated in the cardiology department of the Tver emergency hospital from 03/11/92 to 04/10/92 with a diagnosis of coronary heart disease. Large focal myocardial infarction, asthmatic variant. Complete blockade of the left bundle branch block. Arterial hypertension. H _PA Art.

 Ambulance hospitalized with complaints of suffocation.

 Over 20 years suffering from arterial hypertension. In 1990, a complete blockade of the left bundle branch block was revealed. Over the past year, shortness of breath during normal physical exertion has been bothering. Real deterioration developed suddenly, about 1.5 hours ago: for no apparent reason shortness of breath appeared, quickly developed into suffocation, heaviness in the chest, distance wheezing.

 The condition at admission is serious. Orthopnosis. Severe acrocyanosis. NPV 36 in 1 min. The lungs have hard breathing, a large number of moist rales in all departments. Tones are muffled, rhythmic, heart rate 120 in 1 min. HELL 220/120 mm RT. Art. The liver is 1.5 cm below the costal arch, the feet are slightly pasty.

 On the ECG, sinus tachycardia, complete blockade of the left bundle branch.

In blood tests: Hb 141 g / l, red blood cells 4.4 • 10 ¹² / l, white blood cells 7.9 • 10 ⁹ / l, white blood cell count unchanged, ESR 16 mm / h, AST 1.91 mmol / l, ALT 1.6 mmol / L.

 The level of sphingomyelins on the second day of the disease is 2220 μmol / L of blood, the estimated value of necrosis is 20.8% of the mass of the left ventricular myocardium.

 The acute period of the disease was characterized by recurrent attacks of acute left ventricular failure. In the future, the condition improved slightly, no attacks of cardiac asthma were noted, but shortness of breath with minimal physical exertion remained.

Discharged on the 30th day of the disease with the clinic XHK _PA Art.

 Using the proposed method provides the following advantages compared with existing: the ability to diagnose with greater accuracy (95.7%) myocardial infarction and determine its size with a single study of the level of sphingomyelins in the blood; no need to use expensive equipment, simplicity of execution, the ability to play in any clinical and biochemical laboratory.

Claims (1)

A method for diagnosing and determining the size of myocardial infarction, characterized in that the method of thin layer chromatography determines the level of sphingomyelins in the patient’s whole blood on the second day of the disease and, with a value of the latter above 1900 μmol / l, diagnoses myocardial infarction, the size of which is determined taking into account the level of blood sphingomyelins, myocardial mass left ventricle, necrosis size and calculated by the formula
M = 0.054 • C - 99.1,
where M is the size of the necrosis,% of the mass of the left ventricular myocardium; C is the level of blood sphingomyelins, μmol of phosphorus / l of blood.

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