(57) Abstract:The invention relates to medicine and can be used to treat ischemic heart disease. The invention is a use of dalargin as an antianginal drug. The proposed invention allows to increase the effectiveness of treatment and tolerance to physical loads. table 2. The invention relates to the practice of medicine and can be used to create a new antianginal drug.We used the drug dalargin was synthesized on a Pilot production at the Russian cardiology research industrial complex Ministry of health of Russia.In its structure this connection peptide of the following composition: D-Ala2-Leu5-Arg6-enkephalin .Today we know that dalargin has the ability to accelerate healing of gastric ulcers and duodenal ulcers, as well as hypotensive activity . There are indications on the effectiveness of dalargin in complex treatment of obliterating diseases of lower limb arteries .We first identified its antianginal effect.
< / is. For the treatment of coronary artery disease the most commonly applied nitrovasodilator .However, nitrate is rapidly emerging tolerance, and to achieve the preceding antianginal effect requires a larger dose, and sometimes frequency techniques . At the same time the excess of the optimal doses can cause kollaptoidnoe state of cardiac arrhythmias. In addition, for nitrovasodilators characteristic withdrawal syndrome .There is evidence that peptide agonists opiate receptors can influence the hemodynamics, in particular to reduce total peripheral resistance, thereby reducing postnagruzku on heart muscle . Such changes of Central hemodynamics provides hemodynamic unloading of the myocardium, reduces the need for oxygen, which could have a beneficial impact on the clinical course of CHD.The comparison of these facts and the absence of major contraindications of dalargin allowed us to assume that activation of peripheral opioid receptors may be a new effective approach to the treatment of CHD. In addition, literature data suggest that opioid peptides are virtually unable to penetrate the blood-brain barrier and, with the reason to believe, that opioid peptides can be used in clinical practice, without the risk of drug dependence in patients.The invention will be clear from the following description.The influence of D-Ala2-Leu5-Arg6-enkefalina (dalargin) on the clinical course of coronary artery disease was evaluated in 19 volunteers with angina II and III functional class new York classification. Control group patients (n= 20) with coronary heart disease were treated with placebo (0.9% NaCl). The average age of 482 years. Gender male. The diagnosis of coronary artery disease was verified according to the load electrocardiography and coronaroventriculography. For 5-7 days before the study was canceled reception cardio - and vasoactive drugs, with the exception of nitroglycerin. In this case, the study was started after 1 h after administration of nitrovasodilator.Peptide agonist - and-OR D-Ala2-Leu5-Arg6-enkephalin (dalargin) was administered intravenous bolus dose of 2 mg (28 µg/kg). Sterile lyophilized powder peptide was dissolved in 20 ml of saline and injected into the cubital vein for 2 min injection of placebo and of dalargin was conducted once a day for 1 h before the test on the treadmill and Desk indicators.ECG was recorded in 12 conventional leads on the ECG 6-NEK (Germany). The criterion for the cessation of stress served as signs of failure of coronary circulation. The exercise tolerance was assessed by the distance traveled before the onset of angina, or painless displacement of the ST segment. This indicator is identified as a "painless walking distance" (RBBH).Statistical data processing was performed using the t-student criterion and criterion2.
Clinical example 1. Patient B., aged 45. The history N 0533, Protocol N 38.Came to the office complaining of crushing chest pain with high levels of physical activity and pain in the right calf muscle when walking 300-350 m Sick of 1.5 years. Smokes 30 years. Coronary angiography: occlusive form of coronary artery disease: stenosis of 75% of the PNA, stenosis of 50% OA. Hypokinesia zadnemotornyj segments. Radiographically: seal of the aorta. Calcification bedranol Arte the right external iliac artery, occlusion in the middle third surface bedranol artery.Test on the treadmill. Performed load for 2 min 30 s Criterion of the cessation of stress: a piercing pain in the chest, pain in the right calf, trough-shaped ST segment depression in V4-V6 up to 2 mm (see table.1).After a course of treatment dalargin marked subjective improvement, increased the distance traveled until the pain in his legs. Conducted a medical examination.Test on the treadmill. Performed load within 3 min 45 C. the Criterion for the cessation of stress: angina, ST segment depression "ischemic type" up to 1 mm In right calf small fatigue (see table.2).The frequency of angina attacks before treatment in 3-4 days after treatment 1-2 per day; consumption of nitroglycerin 1-2 tablets a day, after treatment 0-1 per day.Clinical example 2. In 10 out of 19 patients with coronary heart disease after a course of injection of dalargin there was a significant decrease angina with 3,30,8 to 1,20,4 (p<0,05, n=10). At the same time, the 9 people from 19 dalargin had no significant influence on the frequency of angina attacks and the amount of nitroglycerin. However, despite this antiangina the Shih placebo because in this group the frequency of angina attacks and daily consumption of nitroglycerin remained unchanged. In volunteers with positive dynamics of CHD after the course the purpose of dalargin quantity consumed per day nitroglycerin decreased from 2,80,7 to 1,40,7 tablets (p<0,05, n=10). Three episodes of chest pain ceased altogether.The introduction of D-Ala2-Leu5-Arg6-enkefalina patients with coronary heart disease contributed to the increase of the distance of painless walking (RBBH) on the treadmill with 230,7 l 4.6 m source to 340,927,2 m after the course the purpose of the peptide (p<0,01, n=19). When the test is run on the treadmill until the appointment of dalargin criterion for the cessation of stress in 17 patients out of 19 was the appearance of angina, and two people were recorded occurrence of painless depression of the ST segment. After the introduction of D-Ala2-Leu5-Arg6-enkefalina in 17 patients out of 19 criterion for stopping the load was the appearance of chest pain, and two volunteers from 19 as to the purpose of the drug is painless ST segment elevation. The purpose of the placebo had no effect on exercise tolerance.Our results suggest that that ezhednevnich, increases tolerance to physical activity.REFERENCES
1. Korobov, N. Century Dalargin - opiatopodobnyh peptide peripheral actions. Pharmacol. and toxicol., 1988, 4, 35-38.2. Mashkovsky M. D. Medicines. M: New wave, 2000, volume 2 . S. 166-167.3. Blizzard Century. And. Handbook on clinical pharmacology of cardiovascular drugs. M: Malpractice, 1996, 784 S.4. Zoloyev, K., Dudko C. A., Sokolovich, E., Poyarkov C. D., Pourovskii Century. And., Beloglazov, M. E., Evasin N. P., Stepanyan N. A., Shilnikov M, Pathophysiological and clinical evaluation of dalargin for the treatment of obliterating diseases of lower limb arteries. Cardiology. 1990, No. 7, S. 77-79.5. Semerenko M. B., Y. Karpov A. First clinical experience with domestic synthetic peptide of dalargin in patients with ischemic heart disease. Bull. WKNC THE ACADEMY OF MEDICAL SCIENCES OF THE USSR, 1983, 2, 96-98. The use of dalargin as an antianginal drug.
FIELD: medicine, cardiology.
SUBSTANCE: the suggested method should be performed at the background of medicinal therapy with preparations out of statins group, tevetene, polyoxidonium and conducting seances of plasmapheresis by removing 800 ml plasma twice weekly with N 5 due to additional intramuscular injection of immunophan 0.005%-1.0 with N 10 and fluimucyl 300 mg intravenously daily with N 5-10, total course of therapy lasts for 2 mo. The method provides modulation of leukocytic functional activity, moreover, due to altered cytokine profile and, thus, through disintegration of protein-lipid complexes participating in the development of atherosclerotic platelets.
EFFECT: higher efficiency of therapy.
FIELD: medicine, phthisiology, anesthesiology.
SUBSTANCE: during the day of operation one should perform autohemotransfusion, then introduce epocrine intravenously by drops at the dosage of 50-200 U/kg patient's body weight; next day after interference one should inject epocrine subcutaneously at the dosage of 25-100 U/kg; at hematocrit level being below 35% 48 h after operation it is necessary to repeat subcutaneous injection of the above-mentioned preparation at the dosage not exceeding 50 U/kg. The present innovation favors hemopoiesis stimulation in postoperational period, that, in its turn, accelerates postoperational rehabilitation in patients of this group and enables, also, to avoid allotransfusions being dangerous because of immunoconflicting reactions.
EFFECT: higher efficiency of compensation.
1 ex, 1 tbl