RU2487361C1 - Method for evaluating degree of cardiomyocyte cytolysis accompanying infectious myocardial injury - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method for evaluating a degree of cardiomyocyte cytolysis accompanying infectious myocardial injuries consists in examining patient's blood plasma for activities of cardiospecific MB fraction of creatine phosphokinase, α-hydroxybutyrate dehydrogenase or the first and second fractions of lactate dehydrogenase, aspartate transaminase and alanine transaminase. A cardiomyocyte cytolysis index is calculated by formula: CCI=(MB-CPK/MB-CPKN·(α-HBDG/α-HBDGm)·(0.66 (AST/ALT)). The cardiomyocyte cytolysis index is used to evaluate the degree of cardiomyocyte cytolysis accompanying infectious myocardial injuries.

EFFECT: method enables describing the nature of enzymes, evaluating the degree of the change manifestations that is needed to specify the approach to the patient.

2 tbl, 4 ex

Description

The invention relates to medicine, namely to laboratory diagnosis of complications of infectious diseases, can be used to assess the severity of cytolysis of cardiomyocytes in myocardial lesions, developing against a background of various acute infectious diseases.

To date, it has been proven that myocardial damage can develop with any infectious disease. In almost 80% of patients, one or another deviation in cardiovascular activity is detected. Most of them are functional changes and can independently end with the subsidence of the clinical symptoms of the underlying disease in the absence of any special treatment. However, approximately 5% of patients may develop infectious myocarditis with a possible prolonged course, the formation of foci of cardiosclerosis, rhythm disturbances, sometimes of a life-threatening nature, and heart failure.

Due to the complexity of the diagnosis of myocarditis, the need to use a complex of additional biochemical, electrocardiographic and ultrasound methods, the possibility of developing complications a few weeks after the acute phase of an infectious disease, the WHO expert committee proposed using the working term “inflammatory cardiomyopathy”. It is recommended to include all cases of acute and chronic myocardial lesions developing against the background of infectious diseases, including myocarditis and dilated cardiomyopathy.

Adequate determination of the volume and therapy, the selection of the optimal rehabilitation program is impossible without a correct assessment of the severity of violations. To date, severity levels have been proposed only for myocarditis. They are generally based on the intensity of the manifestations of heart failure, including clinical and ultrasound symptoms. However, such violations can be associated not only with the acute process, but also with pre-existing dystrophic and sclerotic processes. This is of particular importance for patients with previous carditis, heart defects, myocardial infarction, in which signs of heart failure are constantly present to one degree or another. Electrocardiographic (ECG) disorders also do not allow us to adequately assess the severity of changes, both due to the possible multifactorial nature of the process and as a result of pre-existing deviations.

It seems possible to draw the most objective conclusion about the degree of cardiomyopathy by the level of activity of cardiospecific serum enzymes released during the breakdown of cardiomyocyte structures. These include the MV fraction of creatine phosphokinase (MV-KFK, or MV-KK), α-hydroxybutyrate dehydrogenase (α-HBDH or an analogue of the 1st and 2nd fractions of total lactate dehydrogenase - LDH). Less specific is aspartic transaminase (ACT). To clarify the reasons for the increase, it is recommended to use the de Ritis coefficient: the ratio of ACT activity to the level of alanine transaminase (ALT), which with a value of more than 1.5 may indicate myocardial genesis of enzyme. However, against the background of an acute infectious disease, the interpretation of laboratory changes can be difficult due to the regular fermentemia that develops against the background of activation of the sympathoadrenal link.

A known method for the early diagnosis of toxic toxic cardiopathy in infants, based on the simultaneous determination of the activity of MV-CPK in serum of venous blood, succinate dehydrogenase (SDH) and glycerophosphate dehydrogenase (GFDH) in capillary blood lymphocytes. With an increase in MV-KFK activity from 9.0 to 16 IU / L and a decrease in LDH from 7.6 to 5.2 g / lymph., GFDG from 6.5 to 4.8 g / lymph. diagnose infectious toxic cardiopathy (RF Patent No. 2200322, IPC G01N 33/573, publ. 03/10/2003) /

The disadvantage of this method is the non-specificity of the lymphocytic reaction and the lack of characteristics of the degrees of severity.

A known method for the diagnosis of acute myocarditis by calculating the coefficients of the ratio of the activity of cardiospecific enzymes in the blood serum (RF Patent No. 2245554, IPC G01N 33/573, publ. 01.27.2005, prototype).

The essence of the method is to determine the relative increase in cardiospecific fractions of enzymes using the formulas:

Kksf-1 = (General LDH - MV-KK) / (General LDH + MV-KK);

Kksf-2 = (LDH total - α-GBDG) / (LDH total + α-GBDG);

Kksf-3 = (general QC - MV-KK) / (general QC + MV-KK).

When Kksf-1≤0.9; Kksf-2≤0.61; Kksf-3≤0.5 diagnose acute myocarditis.

The disadvantage of this method is the lack of interpretation of the severity of violations, which complicates the choice of treatment tactics by a practitioner, does not solve the question of the need and urgency of an additional examination. In addition, the calculation of the coefficient does not take into account the possibility of infectious hyperfermentemia with a characteristic “phenomenon of dissociation”: multidirectional changes in the activity of enzymes that do not require additional cardiotropic treatment.

Thus, when analyzing the results of laboratory tests, it is not always possible to correctly assess the degree of myocardial damage, especially with an uneven increase in indicators.

At present, there are no methods for assessing the degree of hyperenzymemia, and no integrated indicators have been developed to assess the degree of cytolysis, taking into account all available deviations.

The technical problem to which the invention is directed is to determine the degree of cytolysis of cardiomyocytes to assess the degree of myocardial damage in acute infectious diseases, which will ensure the correct choice of treatment tactics and prognosis of the disease.

The stated technical problem is solved by the fact that in the method for assessing the degree of cardiomyocyte cytolysis in infectious myocardial infections, the levels of activity of the cardiospecific MV fraction of creatine phosphokinase, α-hydroxybutyrate dehydrogenase, or the first and second fractions of lactate dehydrogenase and common aspartic amine transamine are determined the degree of hyperfermentemia according to the index of cytolysis of cardiomyocytes, which is determined from the ratio of indicators of levels a ciency for cardiac creatine kinase MB fraction, α-hydroxybutyrate, or the first and second fractions of lactate dehydrogenase, aspartic transaminase and alanine transaminase in the blood serum of the patient of the patient to the corresponding limit values of healthy humans:

ICC = (MV-KFK / MV-KFK _N ) · (α-HBDG / α-GBDG _N ) · (0.66 (AST / ALT)),

where ILC is the index of cytolysis of cardiomyocytes,

MV-KFK - the value of the activity indicator MB (cardiospecific fraction) of creatine phosphokinase in the patient's blood serum,

MV-KFK _N is the limiting value of the activity of MB (cardiospecific fraction) creatine phosphokinase for a healthy person.

α-HBDH is the value of the activity of α-hydroxybutyrate dehydrogenase or the first and second fractions of lactate dehydrogenase in the patient's blood serum.

α-HBDH _N - the limiting value of the activity of α-hydroxybutyrate dehydrogenase or the first and second fractions of lactate dehydrogenase for a healthy person

ACT - the value of the activity of aspartic transaminase in the patient's blood serum.

ALT is the value of the activity of alanine transaminase in the patient's blood serum.

The value of the cardiomyocyte cytolysis index assesses the degree of cardiomyocyte cytolysis in infectious myocardial lesions.

In addition, when the values of the index of cytolysis of cardiomyocytes in the range from 0.01 to 1 evaluate the result as normal and diagnose the absence of cytolysis of cardiomyocytes,

when the value of the index of cytolysis of cardiomyocytes in the range from 1 to 3 is evaluated as the first degree of cytolysis of cardiomyocytes and diagnosed with a mild form of cardiomyopathy;

when the value of the index of cytolysis of cardiomyocytes in the range from 3 to 6 is evaluated as the second degree of cytolysis of cardiomyocytes and diagnosed with a moderate-severe form of cardiomyopathy;

when the value of the cardiomyocyte cytolysis index is more than 6, it is evaluated as the third degree of cardiomyocyte cytolysis and a severe form of cardiomyopathy is diagnosed.

A coefficient of 0.66 before the ratio of ACT and ALT was added to bring the normal ratio of these fractions to 1.

Normal values are entered into the formula in order to be applicable to data obtained in various laboratory conditions.

The method is as follows: in a patient with suspected myocardial infection, blood is taken from an empty stomach vein in a volume of 2 ml, centrifuged at a speed of 1500 rpm for 15 minutes and serum is obtained to determine the levels of MV-CPK, α-GBDH, ACT and ALT using a biochemical semi-automatic photometer and standard sets of reagents for photometric quantitative analysis.

Based on the analysis of the obtained values in accordance with clinical symptoms, data of electrocardiographic and ultrasound examinations, the results of observation in dynamics, the results are interpreted as follows:

up to 1 - normal value, significant cytolysis is absent;

from 1 to 3 - the 1st degree of cytolysis, corresponds to a mild form of cardiomyopathy (acute myocarditis);

from 3 to 6 - the 2nd degree of cytolysis, corresponds to moderate-severe cardiomyopathy (acute myocarditis);

over 6 - 3rd degree of cytolysis, corresponds to severe cardiomyopathy (acute myocarditis).

Examples of specific performance of the method.

Example 1. Patient B., 5 years 1 month.

Hospitalized by an ambulance team with complaints, according to the mother, of vomiting 4 times a day, loose stools without impurities 8 times a day, a rare cough, fever up to 39 ° C.

From the anamnesis of the disease: she became acutely ill when, after breakfast, vomiting appeared after each meal or liquid, frequent liquefied stools. At home she was treated with paracetamol, rehydron. Due to the ineffectiveness of therapy, she was hospitalized.

From the anamnesis of life: regularly observed by the local pediatrician at the place of residence, was not registered in the dispensary. Vaccinated by age.

Upon receipt, a moderate condition. Lethargy. Body temperature 39 ° C. The skin is pale. No swelling. During auscultation: in the lungs, puerile breathing, no wheezing, heart sounds are muffled, arrhythmic, medium-intensity systolic murmur with a maximum at the apex, amplifies in an upright position. Heart rate - 120-140 beats. per minute. Blood pressure - 100/60 mm Hg The stomach is soft. The liver is increased by 1.5 cm. There are no focal neurological and meningeal symptoms.

Clinical diagnosis: acute infectious gastroenteritis. In connection with the first identified clinical symptoms of myocardial pathology, an additional examination was prescribed: a blood test for MV-KFK, α-GBDH, ACT, ALT; ECG examination.

According to the results of a blood test: MV-KFK - 83.7 U / l; α-GBDG - 266.9 U / L; ACT - 60 U / L; ALT - 100 U / L.

CRI = (83.7 / 24) · (266.9 / 182) · (0.66 (60/100)) = 2.05, which corresponds to the 1st degree of cytolysis of cardiomyocytes, mild myocarditis (or cardiomyopathy).

The diagnosis was confirmed by ECG results: sinus tachycardia, decrease in the amplitude of the QRS complex to 7 mm in all standard leads, left ventricular hypertrophy. According to ECHO cardiographic examination: mitral regurgitation of the 2nd degree, slight eccentric left ventricular hypertrophy, ejection fraction within normal limits.

In addition to the basic therapy indicated for the underlying disease, metabolic drugs are prescribed: riboxin 200 mg per day. and asparc 1.5 tablets per day

After 10 days, on the background of recovery from the underlying disease, persistently normal body temperature, the patient was discharged home. On the day of discharge, the condition is satisfactory, heart sounds are audible, systolic murmur is weak, is heard in the projection of the apex. The metabolic therapy was continued on an outpatient basis, the restriction of physical activity was recommended.

After 1 month from the onset of the underlying disease: no complaints. The condition is satisfactory, the skin is without features. Heart sounds are loud, no noise. In the biochemical analysis of blood: MV-KFK - 36 U / l; α-GBDG - 245 U / L; ACT - 48 U / L; ALT - 38 units / liter. CPI = (36/24) · (245/182) · (0.66 (48/38)) = 1.68. On the ECG, a decrease in the amplitude of the QRS complex is preserved, there are no signs of hypertrophy. According to the results of ECHO-cardiography - a positive trend, all indicators are within the age norm. Metabolic therapy continued.

After 3 months from the onset of the underlying disease: no complaints. The condition is satisfactory. With auscultation - without pathology. In the blood test: MV-KFK - 21 units / l; α-GBDG - 118 U / l; ACT - 19 U / L; ALT - 15 units / liter. CPI = (21/24) · (118/182) · (0.66 (19/15)) = 0.45. ECG - a slight decrease in the QRS voltage to 9 mm. ECHO cardiography - without pathology. The treatment is completed.

Conclusion: The use of an integral indicator of the index of cytolysis of cardiomyocytes in this patient allowed us to adequately assess the degree of myocardial damage, choose the tactics of therapy, as well as outpatient treatment and follow-up dynamics.

Example 2. Patient 3., 1 year 6 months.

Hospitalized by an ambulance team with complaints, according to the mother, of repeated vomiting, loose stools up to 8 times a day, fever.

From the anamnesis of the disease: he became ill acutely the day before, when these complaints appeared. I did not receive treatment at home.

From the anamnesis of life: regularly observed by the district pediatrician, is not a member of the dispensary. Vaccinated by age.

On examination: moderate severity. Body temperature - 38.6 ° C. No swelling. There are no wheezing in the lungs. Heart sounds are sonorous, medium intensity systolic murmur with a maximum at the apex, amplifies in a vertical position. Heart rate - 135 beats. per minute. Blood pressure - 90/50 mm Hg The abdomen is soft, the liver is enlarged by 1 cm.

Clinical diagnosis: acute infectious gastroenteritis, moderate form. In connection with the first detected signs of heart pathology, an additional examination was prescribed: a biochemical blood test for MV-KFK, α-GBDH, ACT, ALT; ECG; ECHO cardiography.

In the blood test, MV-KFK - 34 U / l; α-GBDG - 136 U / L; ACT - 34 U / L; ALT - 32 units / liter. CRI = (34/24) · (136/182) · (0.66 (34/32)) = 0.75, which indicates the absence of significant cytolysis and the presence of infectious hyperfermentemia. The result is confirmed by other examinations. On an ECG: sinus tachyarrhythmia. ECHO-cardiographic examination: abnormally located chord of the left ventricle. Additional cardiotropic treatment is not indicated.

1 month after the onset of the underlying disease. There are no complaints. The condition is satisfactory. In the lungs with auscultation - without pathology. Heart sounds are sonorous, a slight systolic murmur at the apex. Heart rate is 105 per minute. In the blood test, MV-KFK - 12 units / l; α-GBDG - 142 U / L; ACT - 28 U / L; ALT - 23 units / liter. CPI = (12/24) · (142/182) · (0.66 (28/23)) = 0.31. ECG - within the age norm. ECHO-cardiographic examination - without dynamics.

Conclusion: The use of an integral indicator of the index of cytolysis of cardiomyocytes in this patient made it possible to ascertain the absence of acute myocardial damage, the presence of regular infectious hyperfermentemia with a previously not diagnosed small heart development abnormality.

Example 3. Patient E., 42 years old. She complained of shortness of breath during physical exertion, discomfort in the heart, fever up to 38 ° C.

From the anamnesis of the disease: I became ill sharply, 3 weeks ago, when a sore throat appeared, an increase in body temperature to 38.5 ° C. The therapist prescribed treatment with local antiseptics (hexoral, strepsils). On the 4th day in connection with the preservation of symptoms, amoxiclav 1000 mg 2 times a day., Zirtec, Linex were added to the treatment. On the 3rd day of antibiotic therapy, there was a decrease in sore throat, a decrease in body temperature to normal values in the morning and to 37.4 ° C in the evening. On the 13th day from the onset of the disease, amoxiclav is replaced by sumamed 250 mg per day. On the 15th day, normalization of body temperature was noted. However, after completing the 5-day course, weakness, sweating, pain in the heart area, shortness of breath with small physical exertion, and an increase in body temperature appeared.

From the history of life: acute respiratory infections 6-8 times a year, acute bronchitis 1-2 times a year, osteochondrosis of the spine, connective tissue dysplasia, mitral valve prolapse, degree 2, from 30 years old - cardiopathy with nonspecific ECG changes.

On examination: moderate severity. Body temperature - 38 ° C. The skin is pale, cyanosis of the lips. No swelling. Lymph nodes are enlarged in the anterior cervical, posterior cervical and axillary groups. The pharynx is loose, the tonsils are hypertrophied (to the 2nd degree). In the lungs, vesicular breathing, no wheezing. Heart sounds are muffled, 110 beats per minute, slight systolic murmur with a maximum at the apex. Blood pressure 85/60 mm Hg The stomach is soft. In a clinical blood test - white blood cells - 10.2; lymphocytes - 52%, ESR - 5 mm / h.

In connection with a suspicion of a heart pathology, an additional examination was prescribed: a blood test for MV-KFK, α-GBDG, ACT, ALT; ECG; ECHO cardiography.

In the blood test: MV-KFK - 38 U / l; α-GBDG - 195 U / l; ACT - 54 U / L; ALT - 16 units / liter. CRI = (38/24) · (195/182) · (0.66 (54/16) = 3.77, which corresponds to the 2nd degree of cytolysis (moderate severity of myocarditis or cardiomyopathy).

On the ECG - sinus tachycardia, compared with previous ECGs, a decrease in the voltage of the QRS complex in standard leads and the appearance of shallow (2.5 mm) negative T waves in the anterior chest leads. With ECHO cardiography, the ejection fraction was 58%, type 1 diastolic dysfunction, focal contractility disorders were not detected, mitral valve prolapse, grade 2. Prescribed treatment: isoprinosine, viferon, elkar, panangin, thromboass, prestarium, coraxan. Against the background of treatment, normalization of body temperature on the 3rd day was noted, a marked improvement in condition.

After 2 months, the patient does not complain, she tolerates household physical activity without deterioration. The condition is satisfactory. The skin is without features. Zev - without pathology. Lymph nodes are not enlarged. Heart sounds are sonorous, no noise. The heart rate is 58 per minute. Blood pressure - 115/70 mm Hg In the blood test, MV-KFK - 16 units / l; α-GBDG - 154 U / L; ACT - 25 U / L; ALT - 22 units / liter. CRI = (16/24) · (154/182) · (0.66 (25/22)) = 0.43, which means the absence of cytolysis. On the ECG - positive dynamics with the normalization of the T waves and an increase in the voltage of the QRS complex. ECHO cardiography also showed positive dynamics with normalization of the diastolic function and an increase in the ejection fraction to 66%.

Conclusion: the use of the integral index of cytolysis of cardiomyocytes made it possible to identify and determine the degree of the newly emerged acute myocardial infectious lesion against the background of previously present changes in the heart muscle with nonspecific ECG changes. Taking into account the 2nd degree of cytolysis, a complex of cardiotropic drugs was prescribed that contributes to the normalization of the state of the myocardium.

Example 4. The use of the index of cytolysis of cardiomyocytes in clinical trials.

Experimentally, 180 complex biochemical studies of the blood serum of patients were carried out with the determination of MV-CPK, α-GBDH, ACT and ALT and the calculation of the cytolysis index of cardiomyocytes.

The results of complex biochemical studies of the blood serum of patients with subsequent calculation of the de Ritis coefficient and the cytolysis index of cardiomyocytes are shown in tables 1 and 2.

Table 1. The levels of activity of MV-CPK and α-HBDH in children with acute intestinal infections. Cardiospecific Enzymes Cardiac Specific Enzyme Activity Levels Children with clinical symptoms of heart pathology with acute renal failure, n = 150 Children without clinical symptoms of heart pathology with AEI, n = 30 U / L % % MV-KFK Less than 24 (normal) 10 fifty 24-48 36 40 48-96 31 7 96-192 twenty 3 192-287.8 3 0 α-GBDG 72-182 fourteen 53 182-273 57 47 273-364 25 0 364-400.4 four 0

Table 2. The values of the de Ritis coefficient and the cytolysis index of cardiomyocytes in children with acute intestinal infections. Cardiospecific indicators The values of cardiospecific indicators Children with clinical symptoms of heart pathology with acute renal failure, n = 150 Children without clinical symptoms of heart pathology with AEI, n = 30 De Ritis Ratio Less than 1.5 39 70 1.5-3.0 41 thirty 3.0-6.0 eighteen 0 6.0-9.42 one 0 Cardiomyocyte Cytolysis Index (ILC) Less than 1 2 93 1 to 3 63 7 3 to 6 32 0 More than 6 12 0

As shown in tables 1 and 2, the activity levels of cardiospecific enzymes and the value of the de Ritis coefficient against acute intestinal infections are higher than normal in some patients who do not have other signs of myocardial pathology, which can be regarded as a natural reaction of the body to activation of the sympathoadrenal system in conditions infectious process. However, without taking into account the degree and characteristics of the enzyme, one can disregard developing cardiomyopathy with mild or inconsistent clinical symptoms in the initial stage. The lack of necessary therapy and regimen restrictions in such patients can lead to an unfavorable course of the process.

From table 2 it can be seen that the increase in the ILC is a more specific indicator for the diagnosis of infectious myocardial lesions. Its increase in isolated cases in the absence of characteristic clinical symptoms indicates the need for further examination and observation of these patients.

Thus, the determination of the index of cytolysis of cardiomyocytes allows us to assess the nature of the enzyme, to determine the severity of changes, which is necessary to determine the tactics of patient management.

Claims (2)

1. A method for assessing the degree of cytolysis of cardiomyocytes in infectious myocardial lesions, which consists in determining the levels of activity of a cardiospecific MV-fraction of creatine phosphokinase, α-hydroxybutyrate dehydrogenase, or the first and second fractions of lactate dehydrogenase, aspartic transaminase and alanine aneminose transaminases, in the blood serum of a sick patient cardiomyocyte cytolysis index, which is determined from the ratio of indicators of activity levels of cardiospecific MV- fractions of creatine phosphokinase, α-hydroxybutyrate dehydrogenase or the first and second fractions of lactate dehydrogenase, aspartic transaminase and alanine transaminase in the patient’s blood serum to the corresponding limit values of a healthy person according to the formula:
ICC = (MV-KFK / MV-KFK _N ) · (α-HBDG / α-GBDG _N ) · (0.66 (AST / ALT)),
where ICC - cytolysis index of cardiomyocytes;
MV-KFK - the value of the activity indicator MB (cardiospecific fraction) of creatine phosphokinase in the patient's blood serum;
MB-KFK _N - the limiting value of the activity of MB (cardiospecific fraction) creatine phosphokinase for a healthy person;
α-HBDH is the value of the activity of α-hydroxybutyrate dehydrogenase or the first and second fractions of lactate dehydrogenase in the patient's blood serum;
α-HBDH _N is the limiting value of the activity of α-hydroxybutyrate dehydrogenase or the first and second fractions of lactate dehydrogenase for a healthy person;
ACT - the value of the activity of aspartic transaminase in the blood serum of the patient;
ALT - the value of the activity of alanine transaminase in the blood serum of the patient,
the value of the cardiomyocyte cytolysis index assesses the degree of cardiomyocyte cytolysis in infectious myocardial lesions. 2. The method according to claim 1, characterized in that when the values of the index of cytolysis of cardiomyocytes from 0.01 to 1 evaluate the result as normal and diagnose the absence of cytolysis of cardiomyocytes,
when the value of the index of cytolysis of cardiomyocytes in the range from 1 to 3 is evaluated as the first degree of cytolysis of cardiomyocytes, and a mild form of cardiomyopathy is diagnosed;
when the value of the index of cytolysis of cardiomyocytes in the range from 3 to 6 is evaluated as the second degree of cytolysis of cardiomyocytes and diagnosed with a moderate-severe form of cardiomyopathy;
when the value of the cardiomyocyte cytolysis index is more than 6, it is evaluated as the third degree of cardiomyocyte cytolysis and a severe form of cardiomyopathy is diagnosed.