Method for predicting lethal result of large-focal myocardial infarction

IPC classes for russian patent Method for predicting lethal result of large-focal myocardial infarction (RU 2246114):

G01N33/53 - Immunoassay; Biospecific binding assay; Materials therefor (medicinal preparations containing antigens or antibodies A61K; haptens in general, see the relevant places in class C07; peptides, e.g. proteins, in general C07K)

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In peripheral blood one should detect the level of CD95(+) and CD16(+) neutrophilic granulocytes and at combination of increased level of CD95(+) neutrophilic granulocytes by 4 times and more and CD16(+) neutrophilic granulocytes by 0.6 times against the norm with ECG signs of myocardial infarction one should predict lethal result of large-focal myocardial infarction.

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FIELD: medicine, cardiology.

SUBSTANCE: in peripheral blood one should detect the level of CD95(+) and CD16(+) neutrophilic granulocytes and at combination of increased level of CD95(+) neutrophilic granulocytes by 4 times and more and CD16(+) neutrophilic granulocytes by 0.6 times against the norm with ECG signs of myocardial infarction one should predict lethal result of large-focal myocardial infarction.

EFFECT: higher accuracy of prediction.

The alleged invention relates to medicine and can be used in cardiology for the treatment of patients with myocardial infarction.

The frequency of myocardial infarction (mi) varies widely, has a tendency to grow and is, according to the who, from 8.5 to 30.0 per 10 thousand people. Due to heavy current, high disability and mortality (total mortality in the acute, acute and subacute periods of THEM is about 30%) timely diagnosis of this disease is one of the urgent problems of modern cardiology. It was compounded by the fact that, until very recently, none of the known methods do not guarantee a reliable diagnosis.

In 1971, the who has developed diagnostic criteria for AMI, widely used by cardiologists all over the world, which include both clinical and instrumental diagnostic criteria in combination with detection of laboratory parameters: clinical picture (typical or atypical chest pain for a period of not less than 30 minutes); ECG changes (monophasic rise of the ST segment and the subsequent pathological Q wave); the Increased activity of the MB fraction of creatine phosphokinase [CPK-MB] and in the early stages and the first fraction LDG at a later date after the attack. (A.L. Syrkin myocardial infarction. 2nd ed. revised and enlarged extra - M.: OOO “Medical information is e Agency.”, 1998. - S).

The disadvantage of this method is that it does not guarantee reliable diagnosis and requires additional clarification of the diagnosis.

Known auxiliary methods of diagnostics of THEM:

Definition total number of blood leukocytes with the determination of total leukocyte blood. The method is as follows. Capillary blood draw in capillary Sali to mark and transferred into a test tube with 3% acetic acid. Suspension of leukocytes fill the camera Goriaev and count nucleated cells in 25 large squares. The resulting figure is multiplied by 50. From whole blood prepared smear and stained by Romanovsky. Count the individual number of different kinds of cells among the total number of propagating cells (100), finding, thus, their percentage.

One of the indirect signs of THEM is early neutrophilic leukocytosis with an increase in the number of band neutrophils.

The main disadvantage of this method is the low specificity, because the changes of these indicators are associated with nonspecific stress reaction, in which leukocytosis may be absent. In addition, these methods do not allow to diagnose the possibility of lethal to THEM (Nvestiga, Nwholesale, Gaudiana, Maskeliya. The complex is securewave study system neutrophilic granulocytes with a possible diagnosis of immunodeficiency in various pathologies. - Method. recommendation No. 96/11. - Krasnodar, 1996. - p.4-5).

There are also known ways to diagnose THEM, which include determining the level of troponin. (Staikova A.A., Staikov D.A. Cardiospecific troponin T in the diagnosis of lesions of myocardial infarction. Cardiology. - 1997. - V.37., No. 6. - P.53-57) the Method is as follows. The level of troponin I and T (ctrt) determine enzyme-linked immunosorbent assay in the serum of patients THEY obtained by centrifugation. Prognostic criteria outcome is an increase in the level of troponin I in the blood higher than the 0.2-0.5 μg/L. the number ctrt increases in proportion to the vastness and depth of the lesion of the cardiac muscle. The disadvantage of this method is that its sensitivity is 100%, only 10 hours later.

For the prototype accepted way to diagnose THEM, which includes evaluation of clinical data and ECG data, blood enzymes (ck-MB fraction, ACT_CINand ALT_CIN) (A.L. Syrkin myocardial infarction. 2nd ed. revised and enlarged extra - M.: OOO “Medical news Agency.”, 1998. - S). Evaluation of clinical data is based on the collection of anamnesis and conducting physical examinations, ECG analysis. The study carried out by reading out electric potential in standard leads, identify enzymes syvorotkina in the dynamics. Diagnostic and prognostic signs are: change of the QRS complex of the ECG, as well as changes of ST segment and excess levels of blood enzymes above normal values.

The disadvantages of this method is that the diagnosis may not be accurate, if at least one of the above criteria are missing. Therefore, there is a need to perform additional diagnostic methods for predicting the course and outcome of THEM. The latter increases the time of examination of the patient, sometimes leading to the most serious consequences due to the untimely adequate intervention in the correction of the patient's condition.

Tasks:

1. Ensuring rapid diagnosis of death to THEM.

2. To increase the reliability of diagnosing THEM.

The technical essence of the method is the following: in the peripheral blood of the patient determine the level of CD95(+) and CD16(+) neutrophilic granulocytes (NG) and increasing the relative amount of CD95(+) neutrophilic granulocytes in 4 or more times the norm and deviation from the norm of the absolute number of CD16(+) neutrophils ±0.6 times, predict fatal myocardial infarction.

The method is as follows. Conducting clinical research, ECG diagnosis and determination of the level of the blood serum enzyme (ck-MB fraction, ACT_CINand ALT_CIN) as well as the determination of the level of blood leukocytes and leukocyte formula. Additionally, survey the level of CD16(+) CD95(+) NG in the peripheral blood using a panel of monoclonal antibodies by chemiluminescence analysis method proposed Avifileopen (Filatov A.V., Bachurin P.F. et al. The study subpopulation composition of human cells using a panel of monoclonal antibodies. // Hematol. and Transfusiology. - 1990. - T.35. No. 4. - p.16-19). When combined increase the level of CD95(+) NG 4 or more times and raising the level of CD16(+)NG 0.6 times with ECG signs THEY predict fatal to THEM. The method was tested on 100 patients to THEM, while in the target group of THEM ended in death in 25% of patients in whom the levels of CD16(+) CD95(+) NG match the specified values. The reliability of the method was 100%.

Examples

1) Dulski YU. (IB No. 1011), 60 years old, was admitted to the intensive care unit 07.05.02 at 13 h 30 min with complaints pressing pain in the chest, radiating to the right hand, which appeared 2 hours ago and have not stopped taking 3 tablets of nitroglycerin. On the ECG: the rise of the ST segment with the subsequent emergence of pathological .Q. in leads V₁-V₄Laboratory indicators of the level of ck-MB, AST_CINand ALT_CINin the limit of the norms the total number of leukocytes 9,4×10⁹/l, blood formula: e-1, P-7, Segm - 74, LF - 14, MES - 4, ESR - 7 mm/h the Level of CD 16 (+) NG - 25% (healthy control - 15%), CD95 (+) NG - 27% (healthy controls 10%) (07.05.02 14.00) Diagnosis: coronary artery disease: Primary from 07.05.02 rear myocardial infarction with paddle Q. cos 2 (Killip). Hypertension 3 tbsp., reasonable, with the defeat of target organs: heart, CHF 1 FKl

2) Fat V.M., 65, entered 09.05.01 at 11 h 30 min with complaints of burning pain in the chest, radiating to the left arm and shoulder, which appeared 4 hours ago, and nausea. ECG: signs of transmural myocardial infarction, anterior localization (ST segment above contours in 1 lead pathological Q wave) Laboratory values 09.05.01 12.30: lake 11,0×10⁹/l, P-8, Segm - 79, LF - 12, Mon-1, ESR - 3 mm/h, AST_CIN- ALT_CINwithin normal limits. CD 16 (+) NG - 20% (healthy controls and 15%, i.e. 0.6 times), CD95 (+) NG - 40% (healthy controls 10% - 4 times). The time of death 19.00 09.05.01. Post-mortem diagnosis: coronary artery disease: Primary from 09.05.01-wave myocardial infarction anterolateral localization, core 2 (Killip). A complication of the underlying disease: Rupture of the myocardium of the anterior wall of the left ventricle in a heart attack. Hemotympanum pericardium (400). Cardiogenic shock.

Example

Ryleev B.C., 63, entered 28.06.01 at 23.30 with complaints of intense pressing pain in region of heart, radiating under the collarbone, which is wound two hours ago.

ECG: signs of transmural myocardial infarction, posterior localization (elevation of ST segment, with the appearance of pathological Q wave).

Blood biochemical parameters: ck-MB, Atkin, Atkin - normal. The total number of cells 12×10⁹/L. blood Formula: e-1, P-4, Segm - 60, LF - 30, Mon - 5. The level of CD16(+) NG - 5% (in the healthy control - 15%), D95(+)NG -30% (healthy controls 10%) (29.06.01 - 24 h 10 min).

Diagnosis: coronary artery disease: Primary, from 28.06.01 back to THEM with a tooth Q. OSP - 3 (Killip). AG - 2 tbsp., reasonable, with the defeat of target organs: heart, HSN - 2 FCL Complication of the underlying disease: Break infarction posterior wall of the ventricle. Hemotympanum pericardium (350). Cardiogenic shock.

The method is tested on 100 patients and can improve the accuracy of identifying possible adverse outcome of myocardial infarction, to reduce mortality in acute myocardial infarction, to reduce the period of stay of patients in hospital when conducting adequate and timely diagnosis of the complications of this disease.

A method for predicting fatal outcome krupnovesovogo myocardial infarction, including a blood test and ECG diagnosis, characterized in that in the peripheral blood to determine the level of CD95(+) and CD16(+) neutrophils and when combined increase the level D95(+) neutrophilic granulocytes in 4 or more times and CD16(+) it is rofiling granulocytes 0.6 times the norm with ECG signs of myocardial infarction predict fatal outcome krupnovesovogo myocardial infarction.