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Aim To evaluate safety and efficacy of sodium adenosine triphosphate (ATP) as a vasodilator in assessment of left ventricular (LV) myocardial perfusion and in verification of ischemia by cardiac volumetric computed tomography (CT).Material and methods The study included 58 patients with suspected ischemic heart disease (IHD). For all included patients, cardiac volumetric CT with a pharmacological ATP test was performed. The rate of adverse effects was analyzed during the ATP infusion. Results of the study were compared with data from using other noninvasive methods for IHD diagnosis by calculating Cohen’s kappa, the measure of agreement between two variables.Results The test performed during CT showed good tolerability of the ATP infusion, a low rate of moderate adverse reactions (8.6 %), and the absence of severe side effects. Results of diagnosing IHD with cardiac volumetric CT with the ATP pharmacological test were comparable with data from using other methods for noninvasive verification of LV myocardial ischemia (bicycle ergometry, treadmill test, stress echocardiography) in combination with coronarography or CT coronarography.Conclusion ATP appears a safe pharmacological agent for diagnosing transient LV myocardial ischemia. ATP can be recommended as a vasodilator for evaluation of perfusion using cardiac volumetric CT.

Aim. To study nicorandil prescription effects before elective percutaneous coronary intervention (PCI) to prevent myocardial injury and 4a type acute myocardial infarction (MI, primary endpoint) and cardiovascular events (CVE) in the first year after PCI (secondary endpoint) in patients with stable coronary artery disease.Material and methods. 182 patients with stable coronary artery disease were included into the study and were randomized into two groups: nicorandil treatment group (n=90) and a control group with a standard medical treatment (n=92). Nicorandil was prescribed orally: 2 days before PCI – 30 mg/day; on the day of PCI – 20 mg 2 hours before intervention and 10 mg 6-12 hours after PCI; over the next 30 days – 30 mg/day. High sensitivity troponin I (hs-Tr) and creatine kinase-MB tests were carried out before PCI, 24 and 72 hours after the intervention; the 4a type MI was diagnosed according to the 4th Universal Definition. Non-fatal myocardial infarction, nonfatal stroke, death from cardiovascular diseases, repeat revascularization (PCI, coronary artery bypass surgery due to aggravation), hospital admissions for angina pectoris recurrence (without interventions) and death from any causes were considered as cardiovascular events. Data on adverse outcomes were collected over the hospital stay, and then 30, 180 and 365 days after the hospital discharge.Results. 4a type MI was diagnosed in 14 patients (8%), in women – 12% and in men – 6%. There was a significant decrease in the incidence of type 4a MI in the nicorandil group (n=3; 3%) compared with the control group (n=11; 12%; p=0.05). Secondary endpoint was recorded in 21% of patients. The relationship was found between 4a type MI and the incidence of CVE the next year after the PCI (p=0.01). In patients with type 4a MI CVE odd ratio increases 5.8 times with confidence interval from 1.5426 to 21.6024. According to the logistic regression analysis the significant relationship between hs-Tr growth 24 hours after the PCI and CVE incidence next year after the PCI was found with cutting value 389.8 pg/ml, AUC=0.641 (p=0.04).Сonclusion. Peroral nicorandil 30 mg/day 2 days before PCI, 20 mg 2 hours before surgery and 10 mg 6-12 hours after PCI, and 30 mg/day next 30 days after PCI decreases the risk of intraoperative myocardial injury and CVE in the next year after PCI.

Aim. To study the possibility of reducing the risk of intraoperative cardiac damage and 4a type myocardial infarction (MI) by administering the oral nicorandil in patients with a stable form of coronary artery disease (CAD) before planned percutaneous coronary intervention (PCI). Material and methods . The study included 182 patients with stable CAD who were randomized to the nicorandil treatment group (n=90) and the control group with a standard treatment (n=92). Nicorandil was prescribed 2 days before PCI (30 mg/day); on the day of PCI — 2 hours before surgery (20 mg orally), 6-12 hours after PCI — 10 mg, later — 30 mg/day within 30 days. The analysis of highly sensitive troponin I (hs-troponin) and creatine kinase-MB (CK-MB) was carried out before PCI and 24, 72 hours after the procedure, the type 4a diagnosis of MI was established according to fourth universal definition. Results . The rate of hs-troponin after 24 hours exceeded the 99th percentile from the upper limit of normal in 146 patients (80%). In the control group, there was a statistically significant more frequent increase in hs-troponin by more than 2000 ng/ml (10% of patients in the control group versus 1% of the patient in the nicorandil group, p=0,038). Type 4a MI was detected in 12% of patients in the control group, and it decreased to 3% of patients in the nicorandil group (p=0,05), and in women it was observed in 21% in the control group and in 3% in the nicorandil group. Among women (n=61), the increment of hs-troponin 24 hours after PCI was statistically significantly lower (287 versus 1135 pg/ml, p=0,04) in the nicorandil group compared to the control group. Conclusion. Reducing the risk of cardiac damage and 4a type MI by nicorandil using before PCI, compared with standard antianginal therapy, is an effective tool in cardioprotection of patients with stable CAD before planned PCI.

The presented clinical observation demonstrates the diagnostic capabilities of cardiac volumetric computed tomography (CT) with a pharmacological test by a vasodilator adenosine triphosphate (ATP) in the simultaneous assessment of coronary anatomy and changes in left ventricular myocardial perfusion (LV) in a patient with painless myocardial ischemia and coronary atherosclerosis. A 68-year-old patient with coronary heart disease (CHD) and atherosclerotic changes in the coronary arteries underwent cardiac volumetric CT in combination with a ATP pharmacological test. The study was performed on a Aquilion ONE 640 Vision Edition computer tomograph (Toshiba, Japan). Assessment of LV myocardial perfusion was carried out in comparison with other clinical, laboratory and instrumental examination methods. The results of clinical and instrumental examination of a patient with a low pre-test probability of coronary heart disease are presented. From the standpoint of modern recommendations on stable coronary heart disease, false-negative results of single-photon emission computed tomography of the heart and stress-echocardiography are discussed. Clinical observation demonstrates the feasibility of diagnosing LV myocardial ischemia by cardiac volumetric CT combined with ATP pharmacological test, confirmed by an invasive determination of the fractional flow reserve. The given clinical example represents the advantage of cardiac volumetric CT, combined with the ATP pharmacological test, as a method for visualizing LV myocardial perfusion in detecting myocardial ischemia.В клиническом наблюдении демонстрируются диагностические возможности объемной компьютерной томографии (КТ) сердца с фармакологической пробой вазодилататором аденозинтрифосфатом (АТФ) в одновременной оценке коронарной анатомии и изменений перфузии миокарда левого желудочка (ЛЖ) у пациентки с безболевой ишемией миокарда и атеросклерозом коронарных артерий. У пациентки 68 лет с ишемической болезнью сердца (ИБС), атеросклеротическими изменениями коронарных артерий проведена объемная КТ сердца в сочетании с фармакологической пробой АТФ. Исследование выполнено на компьютерном томографе Aquilion ONE 640 Vision Edition (Toshiba, Япония). Оценка перфузии миокарда ЛЖ осуществлялась в сопоставлении с другими клинико-лабораторными и инструментальными методами обследования. Представлены результаты клинико-инструментального обследования больной с низкой предтестовой вероятностью ИБС. С позиций современных рекомендаций по стабильной ИБС обсуждаются ложнонегативные результаты однофотонной эмиссионной КТ сердца и стресс-эхокардиографии. Клиническое наблюдение демонстрирует возможности диагностики ишемии миокарда ЛЖ методом объемной КТ сердца с фармакологической пробой АТФ, подтвержденной инвазивным определением фракционного резерва кровотока. Приведенный клинический пример представляет преимущество объемной КТ сердца, совмещенной с фармакологической пробой АТФ, как метода визуализации перфузии миокарда ЛЖ в выявлении ишемии миокарда.

The purpose of the study is to prove the effectiveness of pharmacological preconditioning caused by nicorandil in patients with stable coronary heart disease (CHD) during the elective percutaneous coronary intervention (PCI). Materials and methods. We included 88 patients with a stable form of CHD, who were going to pass the elective PCI, in the study. As the method of blind randomization envelope method was used. There were formed two groups or patients: the first group involved 45 patients - were treated with nicorandil (Cordinic, PIQ-FHARMA LLC) (the main group) the other group included 43 patients who were treated by the standard therapy (the comparison group). The basic antianginal therapy was allowed to use in both groups: beta-blockers, calcium antagonists, ATE inhibitors / angiotensin II receptor blockers, statins, acetylsalicylic acid, blockers of P2Y12 receptor platelets. The admission of prolonged form of nitrates before the PCI was allowed in the second group. Patients from the 1st group were to take nicorandil 2 days and 1 day before the PCI at the 30 mg/day dose, then 20 mg orally 2 hours just before PCI, and one more time 6 hours after the PCI - 10 mg nicorandil. Highly sensitive troponin (HS-Tp) as a biomarker of irreversible damage to the myocardium was evaluated before PCI and after PCI in 24 hours. Were used highly sensitive troponin (HF-Tr) and creatine phosphokinase-MB as an irreversible myocardial damage biomarkers. The analysis of which was conducted before PCI and 24 hours after the surgery. Results. The obtained data shows the significant differences of an increase in hs-Tp in 24 hours after PCI in patients with no admission of nicorandil (117 ng/l) as compared with the nicorandil group (73 ng/l), p = 0.04. There were significant differences in the 24 hours increment in hs-Tp in the control group, it was higher (112 ng/l) than in the nicorandil group (67 ng/l), p = 0.03. There was also a significant decrease in CK-MB after 24 hours in the nicorandil group (2.7 ng/L) compared to the control group (2.0 ng/L), p = 0.008. Also the frequency of the troponin increase above the UNL(upper normal level) in the nicorandal group, was significantly (p = 0.03) lower (in 62% of cases compared to 85% of the control group). Conclusion. The prevention of the complications during the percutaneous myocardial revascularization should be considered with the position of the most suitable pharmacological support. The appointment of the oral form of nicorandil (Cordinic, PIQ-FHARMA LLC) for 2 days and 1 day before PCI 30 mg/day, then 20 mg 2 hours before the PCI and 10 mg after 6 hours after the surgery reduces the risk of intraoperative myocardial damage. The obtained data give an opportunity to extend the indications for nicorandil's appointment in the drug support during PCI in patients with stable coronary artery disease.

This review summarizes current knowledge concerning "nonplatelet effects of P2Y12 receptor antagonist ticagrelor. We show the experimental and clinical evidence that ticagrelor increases plasma concentration of adenosine as a potential mechanism of additive effects of ticagrelor. In addition, we sought to compare the clinical profile of ticagrelor with pharmacological effects of adenosine and discuss from this point of view the effects of ticagrelor on vascular tone, cardiac electrophysiology, ischemia/reperfusion injury, immunity and inflammatory reactions, peripheral nerves.

This review summarizes current knowledge concerning "nonplatelet effects of P2Y12 receptor antagonist ticagrelor. We show the experimental and clinical evidence that ticagrelor increases plasma concentration of adenosine as a potential mechanism of additive effects of ticagrelor. In addition, we sought to compare the clinical profile of ticagrelor with pharmacological effects of adenosine and discuss from this point of view the effects of ticagrelor on vascular tone, cardiac electrophysiology, ischemia/reperfusion injury, immunity and inflammatory reactions, peripheral nerves.

This review is devoted to possibilities of single-photon emission computed tomography (SPECT) combined with pharmacological test with adenosine triphosphate (ATP) to detect myocardial ischemia in patients with ischemic heart disease (IHD). It contains consideration of contemporary problems and limitations inherent in use of pharmacological stress tests in radionuclide diagnostics; discussion of mechanisms of vasodilating effects of ATP in the context of modern concepts of purine receptors; detailed description of technique of pharmacological testing with ATP, as well as contraindications and possible side effects. Experience of foreign studies with the use of ATP stress testing for verification of presence of ischemia in patients with IHD is also presented.

The investigation was undertaken to study the accumulation of the photosensitizer Photosens in arterial atherosclerotic plaques and to immunohistochemically identify cellular elements in them. Specimens were obtained during carotid endarterectomy. The preferential accumulation of Photosens occurred in the plaque areas containing the largest number of cells, such as macrophages and lymphocytes. The photosensitizer accumulated to a greater extent in the unstable plaques than in the stable ones, which seems to be associated with the more marked infiltration of unstable plaques by the cells involved in the inflammatory reaction.

Search of new optimal treatment strategies, allowing to decrease the risk of atherosclerosis development and cardiovascular events is determined by high prevalence of hyperlipidemia in hypertensive patients.To study the vasoprotective effects and security of Valsartan (V) or Fluvastatin extended release (XL) (F) and their combination in stage 1 and 2 essential hypertension (EH) with moderate hyperlipidemia.32 patients with EH after 14 days of wash-out period were randomized to receive either V (160 mg o.d.) or F (80 mg o.d.). After 8 weeks of monotherapy combination of V+F was administered to each patient for the next 8 weeks. At baseline, after 8 weeks of monotherapy, and at the end of the study sitting BP, lipids, NOs level and endothelial function were assessed. Endothelial function was measured as flow-mediated vasodilation (FMD) by high resolution ultrasound. Valsartan (Diovan) and Fluvastatin (Lescol XL) were provided by Novartis Pharma AG (Basel, Switzerland).Combination of F (80 mg o.d) with initial therapy by V (160 mg o.d.) led to more significant decrement of BP and significant improvement of FMD.

To study heart rate variability (HRV) according to 24-h Holter monitoring of ECG in patients with ischemic heart disease (IHD) and to examine effects of tianeptine on HRV.Twenty eight patients with IHD (17 males and 11 females aged 40-70 years) with a verified IHD diagnosis and atherosclerosis of the coronary arteries participated in the trial. Severity of depressive syndrome was assessed by CES-D questionnaire. HR V was assessed by weighted mean variation of the rhythmogram (WMVR) for 24 hours.Initial WMVR (m +/- sigma) in the study group (IHD with depression, n = 15) was 670 +/- 260 ms, in the control group (IHD without depression, n = 13) - 625 +/- 191 ms (the difference was insignificant (p = 0.72). Initial (m +/- sigma) WMVR in men of the study group (n = 6) before therapy was 460 +/- 139 ms that was less than in the control group (633 +/- 183 ms, n = 11).In men HRV depends on duration of the disease. There was a negative correlation between WMVR difference before and after treatment with tianeptine and difference of relevant depression indices with high correlation coefficient (-0.74, p = 0.03).

Two methods of measurement of nitrite and nitrate determination in human serum and plasma (a colorimetric method based on Griess reaction and a HPLC method) have been compared HPLC method revealed extremely low level of nitrites blood plasma, which was roughly the same (about 3 microM or less) in healthy donors, patients with diabetes and hypertension. The level of nitrates in the group of healthy donors (29.9 +/- 2.8 microM) is lower than in patients with diabetes (58.6 +/- 6.9 microM), and in patients with hypertension (35.4 +/- 2.5 microM). Comparison of data obtained by colorimetric and HPLC methods revealed close correlation (r = 0.77, p0.001). Methodical requirements for preparation of samples of serum and plasma of blood for analysis and correct intepretation of results are discussed in view of biochemical properties of nitric oxide molecule.

Functional assessment of endothelium by endothelium-dependent and non-endothelium dependent response of the brachial artery (BA) in patients with risk factors for atherosclerosis.The ACUSON 128 XP/10 unit furnished with linear meter with phase grid (7.0 MHz) was employed in two-direction scanning mode to measure BA diameter at rest, under reactive hyperemia (endothelium-dependent response) and after sublingual intake of 0.01 mg of nitroglycerin (non-endothelium-dependent response) in 12 patients with blood hypertension (group 3), 10 subjects with family hypercholesterolemia (group 2) and 10 healthy subjects (group 1, control).The flow-dependent dilatation remained unchanged in BH patients (9.4%) and lowered in HCE patients (3.0%) compared to controls (9.5%). Nitroglycerin-induced dilatation was not significantly different in patients with family hypercholesterolemia (16.6%), hypertensive subjects (14.5%) and healthy controls (20.5%).The ultrasound method of detection of endothelial dysfunction is demonstrated. Endothelial dysfunction in patients with familial hypercholesterolemia may contribute to development of atherosclerosis.