RU2147250C1 - Method for preventing reperfusion syndrome in acute phase of myocardial infarction period - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves applying laser radiation emitter placed on chest in 2-4 intercostal space 1-2 cm distant from the left edge of the sternum before administering fibrinolytic drugs. Laser radiation is applied at a dose of 3-5 J/cm². Wavelength is equal to 930.0 nm. EFFECT: simplified noninvasive method usable beginning from the first hour of myocardial infarction development. 2 tbl

Description

 The invention relates to medicine, namely to cardiology, in particular to methods for preventing reperfusion syndrome in the acute period of myocardial infarction.

 At present, it is known that when using fibrinolytics followed by lysis of a blood clot in the acute period of myocardial infarction (MI), according to a number of authors, development of reperfusion syndrome (MS) is observed in 20-50%, which is manifested by the expansion of the focus of MI, the appearance of reperfusion arrhythmias (RA) ) and less often - collapse, cardiac asthma [Golikov A.P., Pichurin V.V., Konorev E.A. et al. Limitation of myocardial damage during reperfusion of the coronary artery in dogs using dibunol and its combination with verapamil // Cardiology. - 1987. - N 7 / - S. 66 - 71; Golikov A.P., Polumiskov V.Yu., Berestov A.A. et al. The first experience with the use of the antioxidant dibunol in the acute period of myocardial infarction // Cardiology. - 1984. - N 1. - S. 15 - 18; Chazov E.I. Diseases of the heart and blood vessels. - M .: Medicine, 1992]. To prevent the development of MS in MI, various authors have proposed the use of beta-blockers, calcium antagonists, and antioxidants. However, these methods of treatment were more effective in the experiment than in the clinic [Golikov A.P., Polumiskov V.Yu., Berestov A.A et al. The first experience with the use of the antioxidant dibunol in the acute period of myocardial infarction. //Cardiology. - 1984. - N 1. - S. 15 - 18; Kracij A.M.M. van der Mostert L.H. G., van Etjk et al. Iron-load increase the septibility of Rat Heart to oxygen reperfusion domage. Protection by the antioxidant (1) -Cyani danol-3 and Deferoxamine / Circulation. - 1988. - Vol. 78 - N 2. - P. 442-449; Miyazawa K., Fukuyama H., Komatsu E., Yamagachi J. Effects of propranonol on myocardial damage resulting from coronary artery occlusion followed by reperfusion. // Amer. Heart J. - 1986. - Vol. 111, N 3. - P. 519 - 524]. In recent years, to prevent MS in the acute period of MI, it has been proposed to use laser radiation (LI), which is a prototype, in particular laser irradiation of venous blood (LOVC) with a wavelength of 632.8 nm, as well as irradiation of the myocardium with LI wavelength of 890.0 nm, with a power of 10–15 mW, respectively, the most effective being the use of TWO wavelength 632.8 nm [Olesin AI, Andryushchenko OM, Golub Ya. V. et al. The effect of laser irradiation of venous blood on the protein-synthetic function of cardiomyocytes in experimental myocardial infarction. // Physiological journal. THEM. Sechenov. - 1992. - N 2. - S. 75 - 80].

 The disadvantages are as follows.

 1. The use of LOVA with a wavelength of 632.8 and 890 nm is laborious, it takes 30 to 50 minutes to achieve the required therapeutic dose, which increases the time from the onset of MI to the introduction of fibrinolytics.

 2. When applying VLAF and irradiating myocardial radiation with a wavelength of 632.8 and 890.0 nm, respectively, to prevent MS in the acute MI period, the radiation dose is not taken into account.

 The objective of the invention is to develop a method that increases the effectiveness of the treatment of MS in the acute period of MI.

 The problem is solved in that for the prevention of MS in the acute period of MI they use irradiation of the myocardium LI with a wavelength of 930.0 nm.

The method is as follows. In the acute period of MI, the patient is irradiated with LI myocardium with a wavelength of 930.0 nm using a pulsed laser emitter with an angle of radiation divergence of 3-5 ^o and an average power of 30 - 40 mW. The laser emitter is superimposed on the chest in 2, 3, 4 intercostal space 1 - 2 cm from the left edge of the sternum. The total irradiation power should be from 3 to 5 J / cm ² before the introduction of fibrinolytics. On average, the exposure time of one patient is from 15 to 20 minutes.

 In recent years, when using fibrinolytics in the acute period of myocardial infarction, it was found that the risk of developing MS in the first 1 - 4 hours from the onset of myocardial infarction is 20-30%, while from 4 to 6 hours from the onset of myocardial infarction - 60 - 80%, and after 6 hours, fibrinolytics are either ineffective or when thrombus is lysed, the risk of developing MS is almost 100% [Chazov E.I. Diseases of the heart and blood vessels. - M .: Medicine, 1992.; Braunwald E. Myocardial reperfusion, limitation of infart size, reduction of left ventricular dysfunction and improved survival: should the paradigm be expanded. // Circulation. - 1989. - Vol. 79, N 2 - P. 441 - 444]. Therefore, the search for methods and ways to prevent MS in MI from 4 to 6 hours from the beginning of its development is an urgent problem in modern cardiology practice. It is now known that in experimental studies, OLI in the wavelength range of 780.0 - 960.0 nm has an antiarrhythmic effect, reduces the content of lipid peroxidation products (lipid peroxidation) in both blood and tissues, and also increases the protein-synthetic function of cardiomyocytes with IM [Olesin A.I., Andryushchenko O.M., Golub Y. V. et al. The effect of laser irradiation of venous blood on the protein-synthetic function of cardiomyocytes in experimental myocardial infarction. // Physiological journal. I.M.Sechenova. - 1992. - N 2. - S. 75 - 80]. The use of LI myocardium irradiation in these wavelength ranges and in adequate therapeutic doses [Olesin AI, Pavlova RN, Mazhara Yu.P. et al. A method for determining single and total doses of laser radiation during laser irradiation in the red and infrared ranges. - A positive decision on patent application N. 4773758/14. - 1989; Olesin A.I. , Pavlova R.N., Golub Y.V. et al. Clinical evaluation of the use of laser radiation in various wavelength ranges for the treatment of heart rhythm disturbances in patients with coronary artery disease. // Physical medicine. - 1994. - T. 4. N 1-2. - S. 57 - 58] reduces the activity of lipid peroxidation products in myocardiocytes, improves blood flow through the small arteries, increases hypoxia tolerance of ischemic myocardium, which generally reduces the risk of developing MS with the introduction of phobrinolytics in the acute period of myocardial infarction.

 Examples of specific performance.

Example 1 (prototype):
Patient P., 73 years old, and / b N 6353, was delivered to the cardiopulmonary resuscitation department of NIISP on 04.15.91 2 hours after the onset of anginal status, which developed for the first time. Immediately upon admission, irradiation of the precardial region with an infrared laser with a wavelength of 890.0 μm, a power of 15 mW for 40 min, and systemic thrombolysis with a celiac preparation of 2 million units (intravenous drip on saline for 30 minutes) was performed. On admission ECG - the most acute stage of MI with localization of the anterior wall of the left ventricle (total ST elevation - 8 mm). After 30 minutes, the ST rise is 10 mm, after 2 hours - 14.5 mm, after 24 hours - 7.5 mm. Further, there was a slow dynamics of ECG changes in the area of the focus of myocardial infarction due to the development of pericarditis. Against the background of the introduction of thrombolytic, monotopic ventricular and atrial extrasystoles were noted, an episode of accelerated idioventricular rhythm was recorded. On the 11th day, an ECG examination revealed a rare ventricular extrasystole. With the expansion of the regime - angina pectoris 2 f. K. On the 12th day, congestive wheezing in the lungs was noted once. Estimated volume of necrosis (according to Iosawa I.V., Agladze V.O., Machavariani P.T., Bekauri V.A., Iosava L.I. Relationship between changes in the SE segment on serial ECGs in the acute period of myocardial infarction and final size lesions // Cardiology. - 1985. - N 3. - P. 17 - 20) was 27.5% of the real volume of necrosis (according to Silvestri M., Paterni M., Isardi G., Menutti P., et al. Late thrombolysis in acute myocardial infarct // G. Ital. Cardiol. - 1994. - vol. 24. - N 11. - P. 1359 - 1370) - 24.5%. Discharged for outpatient treatment on the 31st day of illness.

 Example 2

Patient S., 53 years old, and / b N 3342, was delivered to the cardiopulmonary resuscitation department of NIISP on September 12, 94, 2 hours after the onset of the religious status that had developed for the first time. Immediately upon admission, irradiation of the precardial region with an infrared laser with a wavelength of 930.0 μm at a dose of 3 J / cm ^{2 was} started, a systemic thrombolysis with a celiac preparation of 2 million units was carried out (intravenous drip on saline for 30 minutes). On admission ECG - the acute stage of MI with localization in the anterior wall of the left ventricle (total ST elevation is 8 mm). After 30 minutes the ST-12 climb, after 2 hours - 2.5 mm, after 24 hours the ST segment reached isolation. In the future, the regular dynamics of non-penetrating focal changes in the region of the anterior wall of the left ventricle was noted. During the monitoring observation of rhythm disturbances both in the range of thrombolytic therapy, and on the 1st day, as well as other complications during the hospital period, the disease was not observed. Pain did not recur. Estimated volume of necrosis (according to Iosawa I.V., Agladze V.O., Machavariani P.T., Bekauri V.A., Iosava L.I. Relationship between ST segment changes on serial ECGs in the acute period of myocardial infarction and final size lesions // Cardiology. - 1995. N 3. C - 17 - 20) amounted to 29.7%, the real volume of necrosis (according to Silvestri M., Paterni M., Isardi G., Menutti P., et al. Late thrombolysis in acute myocardial infarct // G. Ital. Cardiol. - 1994. - vol. 24. - N - 11. - P. 1359 - 1370) - 12.3%. Discharged for outpatient treatment on the 22nd day of the disease.

 Example 3

Patient K., 64 years old, and / b N 1770 was admitted to the cardioreanimation department of NIISP 2.02.95 2 hours and 15 minutes after the onset of pain behind the sternum, which developed for the first time in my life. The acute stage of posterior myocardial infarction was recorded on the ECG (total rise of the "ST" segment in III, aVF leads was 11 mm). HELL 160/90 mm Hg, pulse 60 beats. in 1 min, rhythmic. Tones are muffled, I tone is weakened, no noise. During auscultation, breathing is hard, moist sonorous rales in the lower parts of the lungs, residual pain behind the sternum. The liver, kidneys, and spleen were not palpable. Systemic thrombolysis was performed: after 3 hours from the onset of adhesion pain, streptase was administered at a dose of 1.5 million units intravenously for 0.5 hours. 30 minutes before the administration of thrombolytic, the precardial region was irradiated with an infrared laser with a wavelength of 990.0 μm at a dose 4 J / cm ² .

 After 30 minutes from the start of treatment, the total ST elevation decreased to 6 mm, after 2 hours to 3 mm, after 24 hours no subepicardial myocardial damage was observed. In the future, there was a natural dynamics of non-penetrating focal changes in the lower wall of the left ventricle. During the monitoring observation of rhythm disturbances both in the dynamics of thrombolytic therapy, so on the 1st day, as well as other complications during the hospital period, the diseases were not observed. Congestion in the lungs was eliminated by the end of 1 day. Pain did not recur. Estimated volume of necrosis (according to Iosawa I.V., Agladze V.O., Machavariani P.T., Bekauri V.A., Iosava L.I. Relation between changes in the ST segment on serial ECGs in the acute period of myocardial infarction and the final size of the lesion // Cardiology. - 1995. - N 3. S. - 17-20) amounted to 31.3%, the real volume of necrosis (according to Silvestri M., Paterni M., Isardi G., Menutti P., et al. Late thrombolysis in acute myocardial infarct // G. Ital. Cardiol. - 1994. - vol. 24. - N - 11. - P. 1359 - 1370) - 17.5%. The patient was discharged for outpatient treatment on the 23rd day from the onset of the disease.

 Example 4

Patient V., 55 years old, and / b N 2796 was admitted to the cardioreanimation department of NIISP 7.04.95 after 1 h 35 min from the onset of pain behind the sternum, which developed for the first time in life. The acute stage of posterior myocardial infarction was recorded on the ECG (the total rise in the "ST" segment in III, aVF leads was 10 mm). HELL 140/90 mm Hg, pulse 70 beats. in 1 min, rhythmic. Tones are muffled, I tone is weakened, no noise. During auscultation, breathing is tough, single dry scattered rales in the lower parts of the lungs, residual pain behind the sternum. The liver, kidneys, and spleen were not palpable. Systemic thrombolysis was performed: after 3 hours from the onset of anginal pain, streptase was administered at a dose of 1.5 million units intravenously for 0.5 hours. 30 minutes before the administration of thrombolytic, the precardial region was irradiated with an infrared laser with a wavelength of 930.0 μm at a dose 5 J / cm ² .

 After 30 minutes from the start of treatment, the total ST elevation decreased to 3 mm, after 2 hours to 2 mm, after 24 hours no subepicardial myocardial damage was observed. In the future, there was a natural dynamics of non-penetrating focal changes in the lower wall of the left ventricle. During the monitoring observation of rhythm disturbances as to the dynamics of thrombolytic therapy, so on the 1st day, as well as other complications during the hospital period, the disease was not observed. Pain did not recur. Estimated volume of necrosis (according to Iosawa I.V., Agladze V.O., Machavariani P.T., Bekauri V.A., Iosava L.I. Relationship between ST segment changes on serial ECGs in the acute period of myocardial infarction and final size lesions // Cardiology. - 1995. - N 3. C. - 17-20) amounted to 33.4%, the real volume of necrosis (according to Silvestri M., Paterni M., Isardi G., Menutti P., et al. Late thrombolysis in acute myocardial infarct // G. Ital. Cardiol. - 1994. - vol. 24. - N - 11. - P. 1359 - 1370) - 15.3%. The patient was discharged for outpatient treatment on the 21st day from the onset of the disease.

To confirm the effectiveness of LI in preventing the development of MS in MI, we conducted experimental studies on 24 outbred dogs. All animals underwent surgery with ligation of the anterior descending coronary artery for 60 min, followed by reperfusion. In all animals, during ligation and after reperfusion, monitor monitoring of ECG indices in the II standard lead was carried out. 10 h after reperfusion, a pathological and anatomical study of the myocardium was carried out, consisting in measuring the area of MI (as a percentage of the area of the left ventricle), according to a modified method of AI Roberts et al (1978) [Robsrts AI, Cipriano PR, Alono DR et al. Evalution of methods for the quanification of experimental myocardial infarction. // Circilation. - 1978. - Vol. 57, N. 1. - P. 35 - 41]. Before ligation of the coronary artery, in three series of the experiment, LOVC was performed with a wavelength of 632.8 nm, a power of 2-10 mW (2 series) and irradiation of the myocardium of LI by fixing laser emitters to the precardial zone with a wavelength of 890.0 nm (3 series) and 930, 0 nm (4 series), with a capacity of 20 - 30 mW and 20 - 40 mW at a dose of 3 - 5 J / cm ^2, respectively. Control was animals that were also subjected to surgery with ligation of the coronary artery for 60 minutes (1 series). Statistical processing of the results was carried out on a computer using the criterion "t" of Student, x ² and standard software packages WORKS, MEZOZAUR, DIASTAT.

 The results of the study are presented in table. 1.

 As can be seen from the data presented, the greatest effect for preventing the development of MS was observed when using VLBF with a wavelength of 632.8 nm and irradiation of the myocardium with a wavelength of 930.0 nm in comparison with irradiation of the myocardium at a wavelength of 890.0 nm.

 It should be noted that the absence of differences in the efficacy of DICA with a wavelength of 632.8 nm and irradiation of the myocardium with LI with a wavelength of 930.0 nm determines a significant advantage of the latter technique in clinical practice: ease of use, non-invasiveness, which allows it to be used from the first hours of MI development, starting from the prehospital phase of medical care. In addition, as shown by previous studies, the effectiveness of the use of LI in these wavelength ranges is due to a decrease in lipid peroxidation, an increase in the protein-synthetic function of cardiomyocytes in the affected sections of the myocardium [Olesin AI, Andryushchenko OM, Golub Ya.V. et al. The effect of laser irradiation of venous blood on the protein-synthetic function of cardiomyocytes in experimental myocardial infarction. // Physiological journal named after I.M. Sechenov. - 1992. - N 2. - S. 75 - 80.].

In the clinic, studies were conducted in 65 patients in the acute-acute period of myocardial infarction. All patients were divided into three groups. Group I consisted of 14 patients with MI who were administered 30 minutes before the introduction of fibrinolytics in the first 6 hours from the onset of the disease (streptokinase, streptodecase, APSAC) of VORP with a wavelength of 632.8 nm, a power of 10 - 15 mW, group II and III were included 12 patients with MI each, who were also irradiated with LI myocardium with a wavelength of 890.0 nm with a power of 10 - 20 mW and 930.0 nm with a power of 20 - 30 mW at a dose of 3-5 J / cm ^2, respectively. The control group consisted of 27 patients with MI using only fibrinolytics. The therapeutic dose of LI with a wavelength of 632.8 nm, 890.0 nm and 930.0 nm was carried out according to a method previously developed by us [Olesin A.I., Andryushchenko O.M., Golub Ya.I. et al. The effect of laser irradiation of venous blood on the protein-synthetic function of cardiomyocytes in experimental myocardial infarction. // Physiological journal. THEM. Sechenov. - 1992. N 2. - S. 75 - 80].

 All patients were assessed for the size of the focus of MI before and in the dynamics of treatment and reperfusion according to generally accepted methods using ECG, echocardiography, and determination of KFK activity. In addition, the real and predicted size of the focus of MI was calculated according to the method of I.V. Iosawa et al. (1995) and M. Siveter et al. (1994) respectively [Iosawa I.V., Agladze V.O., Machavariani P.T., Bekauri V.A., Iosawa L.I. The relationship between changes in the ST segment on a serial ECG in the acute period of myocardial infarction and the final size of the lesion // Cardiology. - 1995. - N 3. C. - 17-20; Silvestri M., Paterni M., Isardi G., Menutti P., et al. Late thrombolysis in acute myocardial infarct // G. Ital. Cardiol. - 1994 .-- vol. 24. - N - 11. - P. 1359 - 1370).

Statistical processing of the results was carried out on a computer using the criterion "t" of Student, x ² and standard software packages WORKS, MEZOZAUR, DIASTAT.

 The results of the study are presented in table. 2.

 As can be seen from the data presented, the largest decrease in the size of the MI focus, MS frequency was observed when LI myocardium irradiation with a wavelength of 930.0 nm was used in comparison with LOVC 632.8 nm wavelength, myocardial irradiation with a wavelength of 890.0 nm and the control group.

Thus, the greatest effect for preventing RA, reducing the size of the focus of MI was observed with preliminary use of irradiation of the myocardium with a wavelength of 930.0 nm at a dose of 3-5 J / cm ² before fibrinolytics.

Claims (1)

A method for preventing the development of reperfusion syndrome in the acute period of myocardial infarction by irradiating the myocardium with laser radiation before the introduction of fibrinolytics, characterized in that the laser emitter is applied to the chest in 2, 3, 4 intercostal space 1 - 2 cm from the left edge of the sternum and is exposed to laser radiation wavelength 930.0 nm in a dose of 3 - 5 J / cm ² .

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