RU2146933C1 - Method of prophylaxis and treatment of patient with myocardium ischemia in coronary-invasive operations - Google Patents

Abstract

FIELD: medicine, cardiology, cardiosurgery. SUBSTANCE: method proposes administration of epytalamine 10-12 h before cardioinvasive operation. Preparation acts as a cardioprotecting agent and ensures to carry out the operation in adult and senile patients. Invention can be used in coronary angioplasty and stenting. EFFECT: enhanced effectiveness of method. 7 tbl, 1 ex

Description

 The invention relates to medicine, more specifically to cardiology, cardiac surgery and interventional radiology, and may find application in coronary angioplasty and stenting.

 Cardiovascular diseases, including coronary heart disease (IVS), are currently the leading cause of death and disability worldwide.

 In recent years, in the United States, mortality from cardiovascular diseases has decreased by 30% due to the massive introduction into clinical practice of such high-tech ways of early diagnosis and treatment of coronary heart disease as coronary angiography (CAG), coronary angioplasty (CAP), stenting (STN), etc. .

 In Russia, due to the limited use of such methods and the late detection of coronary heart disease, mortality from it remains very high. In view of this, each new method aimed at the early detection and prevention of cardiovascular diseases deserves the closest attention from specialists. One of such methods is CAP as a method of revascularization, the positive sides of which are low invasiveness, high efficiency, lack of need for multicomponent anesthesia, the possibility of repeated use, etc. Stenting of the coronary arteries after restoration of blood flow increases the effectiveness of revascularization.

 There are various types of CAP, namely coronary balloon angioplasty, stenting, CAP using a laser or transluminal extraction catheter, etc.

 Based on the palliative nature of CAP, the main goal of such an intervention is to improve the quality of life, the disappearance or improvement of the clinical picture of angina pectoris in the absence or minimization of drug therapy.

 In determining the indications for intervention, another side of the issue must be taken into account - complications can be life-threatening, with a small chance of success of resuscitation if they occur.

 Clinical risk factors for complications include, for example, female gender; senile age (over 65 years); unstable angina pectoris; little experience of the doctor conducting CAP; previously undergone coronary artery bypass surgery; accompanying illnesses.

 Despite the possibility of complications in the presence of chances of success, it is nevertheless necessary to make an attempt to revascularize the myocardium, improve its blood supply in the area of the dilated artery in order to reduce its ischemia. Of course, not in all cases an attempt should be made to CAP. Intervention should be performed in the presence of angiographic indications. Therefore, coronary angioplasty is always preceded by diagnostic coronarography, and recently, CAP is often performed immediately after CAG. This option of simultaneous CAP in combination with CAG is possible in cases when there is a relapse of angina pectoris (up to 6 years) after a previously performed CAP; first-occurring angina pectoris and a recent history of chest pain; relatively high exercise tolerance according to the results of stress tests; unstable angina with proven ischemic changes on the ECG or Holter study; the patient’s young age or the patient’s lack of concomitant diabetes mellitus and a long history of hypertension with recent angina pectoris.

 In such situations, one can most likely rely on a good outcome of the CAP. However, most patients, primarily the elderly, have a number of concomitant diseases and most often expressed atherosclerosis, usually generalized. In view of this, such a contingent of patients requires special preparation for coronary invasive intervention, which increases its safety.

 The present invention relates to a method for additional myocardial protection when performing coronary angioplasty.

 One of the analogues of the invention is a method of performing CAP, in which to prevent the associated artificial ischemia, aspirin and heparin are used (Babunashvili A.M. et al. Coronary Angioplasty, M., 1996, p. 75, 91-91) .

 The method consists in the fact that the patient is prescribed orally 125 mg of aspirin 24 hours before surgery, sleeping pills at night, and in the case of planning a possible implantation of an intracoronary stent, laser recanalization or coronary atheectomy 2 hours before the start of the intervention, an intravenous infusion of reopoliglukin begins 100 ml / h After the introduction of the introducer sheath, 15,000 to 20,000 IU of heparin is administered intravenously or intraarterially to the patient’s artery, adding it throughout the intervention at the rate of 5000 IU per hour and then during the first day at 1000 IU per hour under the control of blood coagulation. In the intensive care unit, the patient is also prescribed aspirin (125 mg per day) and then for 6 months. All these drugs reduce the aggregation of blood cells, reduce its viscosity and therefore are widely used in cardiovascular surgery.

 The authors performed CAP in 292 patients. The main contingent is men (282) aged 40-50 years. Direct angiographic success was achieved in 269 (92.1%) and, as a rule, it was combined with clinical improvement. In 8 cases, acute occlusion of the dilated coronary artery occurred, of which 6 patients developed acute myocardial infarction with a fatal outcome in two. In 15 cases, CAP could not be implemented due to technical difficulties. Repeated CAP as a result of acute occlusion of the dilated artery was undertaken in 3 out of 8, of which in 2 cases an intracoronary metal stent was installed at the site of acute occlusion with good direct effect (arterial lumen and blood flow were restored). Emergency coronary bypass surgery after failed CAP was performed in 2 patients.

 Satisfactory long-term results, clinical and functional, were obtained in 177 of 220 patients examined by the authors (84.3%). Repeated angioplasty at the site of recurrence of stenosis or occlusion of the lumen of a previously dilated coronary artery was noted in 8.1%, coronary bypass grafting after CAP was performed in 1.4%. The remaining patients (6.2%) were prescribed conservative therapy.

 Thus, this method, despite good direct and long-term results, is nevertheless fraught with quite serious complications. It should also be noted that the method was implemented in patients of the middle age group. The method statement does not contain data on the performance of CAP in elderly and senile patients, who, as is known, have a number of concomitant diseases.

 The technical result of the present invention consists in the implementation of CAP mainly in older people, even those of them who were denied the implementation of CAP by known methods.

 This result is achieved by the fact that 10-20 mg of epithalamin is administered intramuscularly to the patient 10-12 hours before coronary angioplasty.

 To expand the scope of coronary invasive interventions in patients with concomitant pathology and elderly people, the world medical practice is constantly searching for means that allow such interventions with the lowest risk of ischemia. These primarily include cardioprotectors, antihypoxants, anti-ischemic drugs.

Among the pharmacological agents proposed for this purpose, the following known preparations passed clinical testing:
- One of the most popular are angiotensin converting enzyme inhibitors. However, as practice shows, they do not improve the course of acute myocardial infarction when they are prescribed on the first day of the disease, not to mention the prevention of myocardial dysfunction in the forthcoming ischemia of it. This does not allow us to dwell on angiotensin-converting enzyme inhibitors as a means of choice for myocardial protection in patients with coronary artery disease.

 - Calcium antagonists, proposed by a number of researchers for this purpose, also did not deserve a positive response. According to the members of the working group on standards for the treatment of myocardial infarction of the European Cardiology Society, "there are no grounds for prescribing calcium antagonists for the prophylactic stage of the acute myocardial infarction."

 An international study of myocardial infarction survival, which studied the use of mononitrates, and the European project for the use of molsidomine in the acute phase of the disease, did not reveal the benefits of using these drugs.

 - A study conducted on 58 thousand patients refuted proposals for the pronounced protective effect of magnesium ions introduced to protect ischemic myocardium.

 - In a 2002 study in patients with angiographically confirmed coronary atherosclerosis, the presence of a rapidly developing clear cardioprotective effect in vitamin E was not confirmed, even a slight increase in acute cardiac death was observed under the influence of the drug, and a significant decrease in the frequency of non-fatal myocardial infarction was recorded only after 1 year of treatment with vitamin E .

 - Intracoronary administration of fluosol (perfluorocarbon drug) during coronary angioplasty helps to reduce the degree of myocardial ischemia during subsequent balloon ballooning in the lumen of the coronary artery. However, the inaccessibility of the drug, the significant cost of the drug, its state of aggregation (a suspension that can block the reticuloendothelial barriers) do not allow us to hope for its speedy and widespread adoption in practical medicine.

 - In the same model of myocardial ischemia created by intracoronary balloon inflation in angioplasty, a steady protective effect showed, judging by the dynamics of the electrocardiographic parameters, intracoronary-administered trimetazidine.

 The closest analogue of the invention is a method for the prevention and treatment of myocardial ischemia in coronary invasive interventions by prior administration of a cardioprotector (Y. A. Schneider et al. "The use of trimetazidine (preductal) for myocardial cytoprotection in the surgical treatment of coronary heart disease." Thoracic and cardiovascular surgery. Moscow, 1996, N 6, p. 281).

 We do not know the use of the epithalamine we have proposed for the protection of the myocardium when performing coronary angioplasty with this study.

 Having been involved in the diagnosis and treatment of patients with coronary artery disease for many years, including repeatedly performing coronary angioplasty, we noticed that myocardial ischemia, artificially created by ballooning in the lumen of the coronary artery, is most difficult to tolerate in elderly and senile patients. This prompted us to search for additional ways to protect myocardium in this category of patients.

 The use of generally accepted pharmacological agents in this situation does not always give a positive result. In this regard, we decided to try the use of geroprotectors, since these drugs normalize the metabolism, immune status and general reactivity of the elderly. Moreover, we began the search for such agents among biologically active substances that are more physiological.

 Our attention was drawn to a preparation containing a complex of polypeptide fractions isolated from the epithalamic-epiphyseal region of the cattle brain that regulates the functions of the endocrine system. The drug is recommended in the treatment of menopause myocardial dystrophies associated with impaired ovarian function.

 Before proposing epithalamine to protect the myocardium during coronary invasive interventions in patients, we conducted a detailed study of it on various models of ischemic heart damage in animals.

 To this end, we investigated its effect upon the administration of massive doses of catecholamines to the animals (heart-like changes in the heart), effects on various types of experimental arrhythmias, effects on isolated heart preparations, and on myocardial energy metabolism.

 Below are the results of these studies.

 The effect of epithalamin on animals when exposed to catecholamines.

 The introduction of massive doses of catecholamines to animals leads to an excessive stimulating effect of the heart muscle with a relative lack of supply of blood and oxygen, which causes heart-like changes in the heart, ECG changes and the appearance of arrhythmia.

 When 0.05 mg / kg of epithalamin was administered to mice intraperitoneally 5 minutes after a lethal dose of isoproterenol (450 mg / kg), its protective effect was detected (Table 1).

 Preliminary administration of 0.5 mg / kg of epithalamine to rats (15 minutes before the administration of 1.7 mg / kg of adrenaline) also reduced the death of animals by more than 2 times (Table 2).

 In another series of experiments, rats were injected with a freshly prepared solution of adrenaline ("Serva") intraperitoneally at a dose of 2 mg / kg, then after 1 and 3 hours - epithalamine at a dose of 0.5 mg / kg. In preliminary experiments, it was found that the maximum activation of lipid peroxidation (lipid peroxidation) is observed one day later, and changes in the activity of respiratory enzymes are most pronounced several hours after the administration of adrenaline. Therefore, the slaughter of animals to determine the content of lipid peroxidation products and the activity of dehydrogenases was performed at different times. Diene conjugates (DC) and malondialdehyde (MDA) were determined immediately after slaughter in pieces of the left ventricle of the heart and liver, and the activity of dehydrogenases and glycogen content were determined histochemically in cryostatic sections after freezing and storing pieces of the left ventricle in liquid nitrogen.

 Administration of epithalamine to rats with strong adrenergic stimulation significantly reduces the intensity of the adrenaline-activated lipid peroxidation process, especially judging by the content of diene conjugates in the heart and liver every other day (Table 3).

 When determining the activity of dehydrogenases and glycogen content in the first hours after administration of adrenaline, reliable data were obtained on the change in a number of studied parameters (Table 4).

 Thus, epithalamin, both before and after exposure to a massive dose of exogenous adrenaline, has a protective effect on experimental animals, which is expressed in a decrease in mortality and a decrease in lipid peroxidation processes. The beneficial effect of epithalamin on energy metabolism is manifested in the normalization of the activities of lactate dehydrogenase and succinate dehydrogenase (LDH, LDH), glycogen retention under the studied conditions.

The effect of epithalamin on various types of arrhythmias
We studied the effects of epithalamin on two models of experimental arrhythmias: adrenaline and calcium chloride. The adrenaline model is more physiological, related to rhythm disturbances arising from excessive adrenergic stimulation of the heart, its ischemic damage.

 Two series of experiments showed that preliminary administration of 0.5 mg / kg of epithalamin to rats before intravenous administration of adrenaline had a significant decrease in the number of extrasystoles by 2–3 times and in this case the effect was comparable with the effects of 10 and 20 mg / kg of cordarone.

In rats anesthetized with urethane, the protective effect of epithalamine was studied in doses from 0.025 to 20 mg / kg on a model of potassium chloride arrhythmia (200 mg / kg intravenously 10% CaCl ₂ solution) in comparison with novocainamide (40 mg / kg). It was shown that epithalamin dose-dependently exerts a protective effect against large concentrations of arrhythmogen (Table 5).

 In this model, a dose of 1 mg / kg epithalamin was ineffective. In addition, during the experiments, the property of epithalamin, administered intravenously in a wide range of doses (from 0.025 to 20 mg / kg) to anesthetized rats, to change the heart rate (HR) was revealed. So, in 6 rats (out of 50) with initial bradycardia, the heart rate increased by 5.3-57.7%, in only one rat the initial heart rate was normal, but with the administration of epithalamine at a dose of 0.1 mg / kg it increased due to a decrease tooth width T.

 On the contrary, in two rats with initial tachycardia, epithalamin somewhat reduced heart rate due to the lengthening of the T-P and PQ intervals. At a higher dose (20 mg / kg), the ability of epithalamin to reduce heart rate even at its normal value and to slow atrioventricular conduction without a decrease in heart rate was noted, which is a common pattern of exposure to large doses of the drug.

 The results obtained on the rapid effect of the introduced epithalamin on the electrical activity of the heart indicate that in this case the drug does not affect the condition of the contractile apparatus and bioenergy processes in cardiomyocytes, but, first of all, directly on the cell membrane, causing a change in ion permeability, depolarization and generation action potential.

 One of the explanations for the protective effect of epithalamin with adrenaline and calcium chloride arrhythmias may be that the drug prevents the excessive influx of Ca + 2 ions into the cell, which is associated with adrenergic stimulation (receptor sensitivity to catecholamines, cAMP (cyclic adenosine monophosphate) -dependent Ca-phosphorylation ), and with direct entry of Ca + 2 into the cell with each cycle of contractions with its increased content in the medium.

 The effect of epithalamin on isolated cardiac drugs.

 Studies on heart preparations seemed necessary to clarify the direct effect of epithalamine on the heart, since systemic administration cannot exclude the possible involvement of the central nervous system and endocrine system in the reaction to the drug. The research objective included, in addition, the study of the dose-dependent effects of epithalamin and its effect on the functioning of isolated cardiac drugs during ischemia, exposure to various agents and mediators.

 When perfusing the isolated heart of a guinea pig according to Langendorff, it was shown that the effect of epithalamine directly on the heart in small concentrations, correlated with available therapeutic doses, does not affect the contractility of a normal heart. The drug to a greater extent and primarily reduces the strength of contractions than reduces the rhythm.

 Total cardiac ischemia was created by completely squeezing the hose supplying the perfusion solution for 30 minutes. Then reperfusion was started under the same conditions as before ischemia (control). To determine the effect of epithalamin on the studied parameters, perfusion was performed in the presence of various concentrations (0.2-5.0 μg / ml). We recorded mechanical contractions; during the experiment, biopsy samples were taken several times from the top of the heart, weighing about 10 mg, where the content of malondialdehyde was determined. Hearts at the end of the experiment and part of the control hearts before ischemia were quickly cut and frozen in liquid nitrogen, where the contents of ATP, ADP and AMP (adenosine tri-, di- and monophosphates) were determined.

 The constant presence of epithalamin in the perfusate in doses of less than 1 μg / ml favorably affects the work of the heart and its experience of an ischemic condition under these conditions. There is a tendency to an increase in the strength of contractions after ischemia compared with the control, which is confirmed by the greater preservation of macroergic phosphates in the heart, while the content of MDA does not significantly differ from the control.

The study of the effect of epithalamin on the restoration of the contractility of rat hearts after a period of ischemia was carried out in a more intense mode of work of the heart muscle: with an imposed rhythm of contractions and an increase in the temperature of the perfusion solution to +37 ^o C.

 It was found that the addition of epithalamine after the end of ischemia at a concentration of 100 ng / ml or less to the fifth, especially to the tenth minute of reperfusion, led to an improvement in contractile function; the amplitude of contractions (AS), the speed of contractions and relaxation, the coronary duct increased and cardiac contracture decreased slightly compared to the control (Table 6).

 In another series of experiments, epithalamine was added to perfusate 10 minutes before ischemia. Under these conditions of tight stimulation (frequency 5 Hz), control hearts did not restore normal contractile activity during reperfusion. Sustained fibrillation and an increase in contracture ensued, which led to the absence of any contractions after 5 minutes of reperfusion.

 It is noteworthy that the preliminary administration of epithalamin not only restrained the growth of contracture during the period of ischemia, but also contributed to its decrease as the heart reperfused, which affected the increase in the coronary duct. A characteristic feature of the action of epithalamin in this series of experiments was that there was an increasing recovery of the contractile activity of the heart during reperfusion.

 Thus, the preliminary administration of epithalamin prevented the development of ischemic contracture, protected the heart, which was on the verge of stopping, from fibrillation and a catastrophic decrease in contractile activity, on the contrary, restoring it. That is, the protective effect of the drug is realized primarily during the period of ischemia, and this is the effect of its very small doses - under these conditions, it manifests itself at an epithalamine concentration of up to 1 pg / ml.

The effect of epithalamin on myocardial energy metabolism
Rats were injected intraperitoneally with a necrogenic dose of adrenaline ("Serva") - 2 mg / kg, and 0.5 mg / kg of epithalamine was administered in parts of animals after 0.5 and 1.5 hours. After 2-3 hours from the moment of administration of adrenaline, rats were sacrificed by decapitation, hearts were placed in chilled physiological saline and thin sections 0.5 mm thick were prepared in the cold. After this, part of the slices were frozen in liquid nitrogen, and part was placed in Petri dishes with medium 199, where they were incubated for 10 min at +37 ^° C, followed by freezing in liquid nitrogen. The growth of lactate in myocardial tissue during incubation of sections in vitro was determined.

 Incubation of sections of the heart of rats in vitro, that is, the creation of ischemia in the tissue, after 10 minutes led to an increase in the lactate content in all groups, but more in rats with preliminary administration of adrenaline. As a result, the content of lactate in the hearts of normal rats increased by 2 times, adrenaline - by 7.4 times, and in rats with subsequent administration of epithalamin - by 3.5 times.

 Administration of adrenaline to rats after 3-4 hours led to a decrease in glycogen stores in the heart and an increase in LDH and LDH activity. That is, epithalamin contributed to a decrease in the intensity of oxidative metabolism stimulated by exogenous adrenaline. Apparently, in rats with the introduction of massive doses of adrenaline, along with the activation of glycolysis, aerobic respiration efficiency is limited, and the administration of epithalamin to such rats makes lactate fluctuations less pronounced.

 A characteristic sign of damage to myocardial cells during hypoxia and ischemia is a violation of the respiratory function of mitochondria. Apparently, one should distinguish between the degree of oxygen deficiency, on which changes in the processes of oxidation and energy generation in the cell depend. So, with moderate hypoxia, glycolysis is enhanced, and aerobic oxidation, due to the activation of the NADH- (nicotinamidine nucleotide H) -oxidase pathway, copes with the oxidation of lactate, ensuring the synthesis of ATP. This stage of the response of the heart to oxygen imbalance is associated with the activation of compensatory mechanisms of energy generation.

 In a transitional state, depletion of glutamate reserves and the gradual accumulation of succinate in the heart already occur. As deep hypoxia is achieved, a decrease in the efficiency of aerobic oxidation is observed, which is manifested in the steady accumulation of lactate and the inability to utilize it, a significant increase in the activity of LDH, and the limitation of NADH-dependent oxidation. Moreover, an increase in the content of NADH in the cell precedes the accumulation of lactic acid. The first changes with an increase in the degree of oxygen deficiency occur precisely on the NADH-dependent portion of the respiratory chain, the functioning efficiency of which decreases, while maintaining the activity of the terminal portion of the chain - cytochrome oxidase. Often, an increase in the activity of LDH in oxygen deficiency is seen as a necessary compensatory mechanism that helps maintain heart viability. However, with the aggravation of hypoxia, a significant activation of the succinate oxidase pathway usually occurs and in parallel a catastrophic inhibition of the NAD-oxidase oxidation pathway necessarily occurs.

 Apparently, there is a discoordination of these two alternative but interconnected oxidation pathways, and in order to maintain optimal conditions for the succinate oxidation, the presence of NADH oxidase activity is required, which determines the resistance of animals to hypoxia.

 A state where there is a steady increase in the activity of LDH, usually associated with a significant inhibition of the NADH-oxidase pathway, that is, when a hyperactive LDH monopolizes the respiratory chain, signifies deep-seated changes in the functioning of the respiratory chain of mitochondria. By the degree of stimulation of oxygen consumption caused by the addition of succinate to cardiomyocytes, the extent of their damage is judged.

 In our studies, it was shown that the addition of succinate (10-4M) to a suspension of cardiomyocytes causes respiratory stimulation, depending on the oxygen regime. So, with the addition of succinate to hypoxic cells, respiration was intensified by almost 6 times or more with respect to the endogenous level of oxygen consumption.

 The addition of succinate to oxygenated cells with a more favorable energy status, whose endogenous respiration level was initially higher, only slightly increased oxygen consumption. It was found that the addition of epithalamin (1 ng / ml - 10 μg / ml) to a suspension of cardiomyocytes, respiration of which was stimulated under hypoxia with succinate, in some cases (up to 0.1 pg / ml) caused a dose-dependent inhibition of LDH activity similar to malonate. At the same time, epithalamin did not inhibit respiration stimulated by the addition of NAD H2. Thus, the corrective effect of epithalamin on the redistribution of metabolic flows in the respiratory chain of mitochondria, changed under the influence of hypoxia, was shown. In order to elucidate the direct effect of epithalamin on the activity of LDH, histochemical studies were performed on freshly prepared cryostat sections of rat hearts. The reaction conditions were selected so that it was possible to evaluate the effects of a competitive LDH inhibitor, malonate. At a concentration of succinate of 1 mmol, the addition of 5 mmol of malonate to the reaction mixture caused an almost complete (93%) inhibition of the reaction. As a result of the studies, it was found that the addition of 100 μg / ml epithalamine to the solution (at lower concentrations, an inhibitory effect was not manifested under these conditions), an inhibition of the activity of LDH by 18-55% was observed.

 Apparently, the ability of epithalamin to have a direct inhibitory effect on succinate dehydrogenase activity, which can be observed in certain conditions (for example, ischemia) in vivo, is primarily associated with the penetration of the inhibitory principle into the cell and its direct effect on the enzyme.

 Thus, the energy-saving effect of epithalamin is expressed in restraining glycolysis, increasing the efficiency of oxidative phosphorylation in mitochondria, which helps to increase the viability of cardiomyocytes and makes them more resistant to oxygen deficiency. As a result of the action of epithalamin during hypoxia and ischemia, glycogen stores are not depleted, the activity of LDH, LDH decreases, the activity of NADH-DG is maintained. Energy metabolism goes into a different state, becomes more economical, maintaining or maintaining its effectiveness at a sufficient level.

 Summarizing the results of studies of epithalamin on animals in experimental models of myocardial damage, which demonstrate with a high degree of certainty its positive properties, manifested in a decrease in mortality, normalization of enzyme activity, metabolism, stabilization of cell membranes and energy-saving action, we can confidently say about its protective effect on the myocardium .

 These positive properties of it and the absence of side effects allowed us to conduct clinical testing of the drug in the elderly, in particular with coronary artery disease and in the early post-infarction period.

 We give examples of the use of epithalamin when performing coronary angioplasty in the elderly.

 Example 1. By-L., 75 years old, was admitted to the cardiopulmonary resuscitation department of the St. Petersburg Clinical Hospital named after L.G. Sokolova January 10, 1999, in a moderate state with complaints of frequent chest pains of a compressive nature that have become more frequent in recent days, radiating to both hands and the lower jaw; an emergency doctor was called several times, the last pain attack was stopped by intravenous administration of promedol. From the medical history of the disease, it is known that anginal pain has been disturbing for about 10 years, has been stopped by taking nitroglycerin under the tongue. It is also known that during the same period of time there were transient rises in blood pressure up to 200/100 mm Hg, "working" numbers AD-140/80 mm Hg. Art. Regarding arterial hypertension and coronary heart disease, I constantly took nitrates, atenolol, preductal, capoten, aspirin in the last year. During a previous hospitalization in December 1998, the patient underwent drug treatment in the cardiology department with similar complaints and clinical presentation. Given the age of the patient, the issue of coronary angiography to address the tactics of further treatment of the disease was not considered by the specialists of the department. Based on the data of anamnesis, laboratory and instrumental studies, the patient was diagnosed with coronary heart disease, progressive angina pectoris, hypertension (hypertension) II stage, type II diabetes mellitus (subcompensated), cholelithiasis (cholelithiasis) (condition after cholecystectomy).

 Due to the weak effect of the ongoing drug therapy and to clarify the diagnosis, the patient was offered selective coronary angiography. Given the age of the patient, the presence of concomitant diseases, it was decided to prescribe epithalamin before surgery.

 January 11, 1999, on the eve of surgery at 20 hours, the patient took 325 mg of aspirin, after which at 22 hours she was injected intramuscularly with 20 mg of epithalamin. On the morning of January 12, 1999, under local anesthesia of 20 ml of a 1% novocaine solution, selective angiography of the coronary arteries was performed according to the Jatkins method and the following coronary lesion was found: the right type of coronary blood flow; left main trunk - without features; the descending branch - signs of atherosclerosis without hemodynamically significant stenosis, the envelope of the artery - a small subocclusion in the middle third, the right coronary artery (PKA) - subocclusion in the middle third, a weak filling of the periphery (anterograde). The nature of the lesion, the presence of minimal anterograde blood flow in the PCA, the patient's readiness and her good clinical condition led to the decision to perform angioplasty of the PCA immediately after coronarography. During the diagnostic procedure, the maximum blood pressure is 150/90 mm Hg, the rhythmic pulse is 72 beats in 1 min. The patient was administered intravenously 15,000 units of heparin. To perform angioplasty, the right Jadkins 8F guide, a 3.0x30 mm World Pass balloon (Cordis) and the ACS Hi-Torque Floppy guide (0.14) were chosen. After installing the guide at the mouth of the right coronary artery (PKA), the conductor succeeded in passing the occlusion site, moving it into the distal segment of the vessel and bringing the balloon to the site of narrowing. 2 consecutive inflation was performed at 4 atm lasting 1 min each and after the control injection of contrast - 6 atm lasting 3 min. The whole procedure lasted for 20 minutes. When the balloon was inflated, a transient short-term reverse displacement of the ST segment was noted on the electrocardiogram. The patient did not experience chest pain. A satisfactory angiographic result was recorded on the final angiogram (residual stenosis 15%). After transferring the patient to the intensive care unit, there was no data for acute closure of the vessel, the postoperative course was smooth. The patient was transferred to the ward on January 16, 1999, from which, after correction of therapy, the patient was discharged for outpatient treatment.

 At the follow-up examination after 4 months, the patient did not complain of angina attacks or their equivalents, according to laboratory and instrumental studies, there were no signs of myocardial ischemia.

 To date, the proposed method has treated 19 patients over the age of 60 years (of which 5 - 70-75 years, the rest - 60-70 years) with a diagnosis of IHD and progressive angina pectoris and 3 patients aged 65-79 years with IHD, operated in the early post-infarction period with subsequent stenting.

 In all 22 cases, we did not observe serious complications, there were only hematomas at the puncture site (2 cases), hemodynamic disorders that did not require special treatment (2 cases), pain (6 cases) when the balloon was inflated, stopped with nitroglycerin, and not in one case that did not require the use of narcotic drugs.

 The results of interventional interventions are analyzed in comparison with the age-comparable control group N 1 (15 patients aged 60 to 72 years), as well as with the N 2 group (72 people under 60). It was found that in such indicators as the duration of hospitalization in the intensive care unit, the frequency of complications and the activity of creatine phosphokinase (CPK) the next morning after the procedure, patients protected by epithalamine differ from their peers for the better and are not inferior to young people (Table 7).

 The proposed method in comparison with the known has several significant advantages.

 1. The method allows you to perform coronary angioplasty in elderly patients, up to 75 years, even those of them who had previously been denied such surgery.

 2. The method significantly reduces the number of complications. In none of the interventions that we performed did we observe a violation of the heart rhythm or re-infarction, while, for example, the nitrates used in such interventions significantly change the hemodynamics and heart rhythm, reducing pressure and heart rate. We have not had a single lethal outcome from the 22 cases of coronary angioplasty that we have performed to date.

 3. The method reduces the length of stay of the patient in intensive care to 3-4 days.

 The method was developed at the St. Petersburg Institute of Bioregulation and Gerontology of the SZO RAMS and was clinically tested in the cardiac resuscitation department of the St. Petersburg Clinical Hospital named after L.G. Sokolova in 22 patients with a positive result.

Claims (1)

 A method for the prevention and treatment of myocardial ischemia in coronary invasive interventions, including the preliminary introduction of a cardioprotector, characterized in that 10 to 12 hours before the coronary angioplasty is performed, 10 to 20 mg of epithalamin is administered as a cardioprotector.

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