Chronotropic action of immobilized subtilisins during the perfusion of an isolated rat heart

The pharmacological experiments on isolated organs (ex vivo) are the preferred method for assessing the primary pharmacodynamics of the studied drugs, since this method is completely excluded the systemic influence of neurohumoral regulation. In the last decade, a new group of thrombolytic drugs based on immobilized subtilisins has been formed. At the stage of registrational preclinical and clinical studies, their pleiotropic pharmacological effects have not been studied. Meanwhile, there is a reason to consider that their pharmacological activity in the bloodstream is not limited to thrombolytic action, but may be extended to a systemic effect on the cardiovascular system. The aim of the study was to investigate the chronotropic effects of an isolated heart during its perfusion with solutions of immobilized subtilisins at different concentrations. Material and methods. The isolated rat heart model according to Langendorff was used in the study. The experiment included 50 Wistar rats, which were divided into 5 groups: isolated hearts perfused only with Krebs – Henseleit solution (control) or with immobilized subtilisins in 4 concentrations (170, 340, 510 и 1020 U/l). Results and discussion. The immobilized subtilisins have a negative chronotropic effect. The onset of the effect depends on the drug concentration in the solution: the higher concentration, the earlier effect. From 5 to 10 minutes of perfusion, a negative chronotropic effect is observed using of immobilized subtilisins at any dose. The duration of its increase is manifested up to 10–20 minutes, depending on the drug concentration in solution. After 20 minutes of perfusion, the achieved negative chronotropic effect remains at a plateau level up to 40 minutes. Conclusion. The immobilized subtilisins have an independent pharmacological effect on heart rate

Studying the pharmacokinetic parameters of new normothymic drug based on the complex of lithium citrate, aluminum oxide and polymethylsiloxane

For the treatment of bipolar affective disorders, lithium preparations are the most famous and effective. But the main problem with the use of lithium preparations is the narrow «therapeutic corridor». An urgent task is the creation of dosage forms of lithium with a slow release and a wide therapeutic range. The study object was a new normotymic drug based on lithium, aluminum oxide and polymethylsiloxane. Due to the new carrier matrix lithium is released from its porous structure gradually providing a prolonged effect and maintaining an optimal concentration in the blood which also helps to minimize side effects. The purpose of the study was to explore the pharmacokinetic parameters of a normotymic drug based on a complex lithium citrate, aluminum oxide and polymethylsiloxane (LOAP).Material and methods: for the assessment of pharmacokinetic parameters the method of atomic emission spectrometry with inductively coupled plasma and two-chamber modeling were used.Results and discussion. The pharmacokinetic data showed a linear nature of pharmacokinetics of the drug based on LOAP as the foundation of data of the lithium’s amount in the blood plasma of rabbits after intragastric administration at doses of 200, 400 and 800 mg/kg. The drug with intragastric administration at a dose of 800 mg/kg is well absorbed from the gastrointestinal tract, with bioavailability (F) 74 %. This dose shows the maximum increase of the area under the pharmacokinetic curve (AUC - 32787.1 (ng x h)/ ml), and indicators of elimination constant (Kel - 0.062 h-1), clearance (Cl - 0.09 l/(kg x h)), elimination half-life (T1/2p - 11.436 h) in comparison with other doses remain unchanged

GENDER DIFFERENCES OF ANTHROPOMETRIC CHARACTERISTICS, APPROPRIATE HEART RATE AND THE STRESS RESISTANCE INDEX OF EARLY ADOLESCENTS LIVING ON THE TERRITORY OF KRASNODAR KRAI AND THE REPUBLIC OF KABARDINO-BALKARI

Aim. To find out gender features of anthropometric characteristics, to define average index value of stress resistance of young teenagers living on the territory of Krasnodar Krai and the Republic of Kabardino-Balkaria.Materials and methods. Data on body height, weight, arterial blood pressure and pulse of 140 children (70 girls and 70 boys) at the age of 13,2±1,6 years living in the Republic of Kabardino-Balkaria as well as 137 children (70 boys and 67 girls) at the age of 13,4±0,1 year living on the territory of Krasnodar Krai (The Belorechensk and Crimean Districts) are collected and subjected to the statistical analysis. The appropriate number of heartbeat, total body area, the level of endured stress were determined by the formulas developed by Yu.R. Sheykh-Zade. Digital material is processed by the method of variation statistics in the Microsoft Excel program.Results. The carried-out statistical analysis showed that anthropometric parameters are lower in thirteen-year old boys living in the Republic of Kabardino-Balkaria than in inhabitants of various parts of Krasnodar Krai: body weight (47,63±1,75 and 52,56±1,02 kg respectively), body area (14279,54±176,54 and 15109,95±181,67 cm2 respectively), index of body weight (19,12±0,21 and 20,43±0,30 c.u. respectively). Girls at the age of thirteen living in the Republic of KabardinoBalkaria have lower physiological parameters in comparison with inhabitants of Krasnodar Krai: the appropriate number of heartbeat (68,31±0,54 and 70,78 ±0,39 min-1 respectively), stress resistance index (1,14±0,23 and 1,28±0,05 c.u. respectively).Conclusion. Gender differences of anthropometric and physiological parameters in children of the early teenage period between the stated regions (Krasnodar Krai and the Republic of Kabardino-Balkaria) are determined

Анализ взаимосвязи параметров легочной гемодинамики с выраженностью клинических проявлений у больных хронической обструктивной болезнью легких: возможности лекарственной терапии

Objective: to assess pulmonary hemodynamics and the presence of systolic and/or diastolic dysfunction of the myocardium of the right and left ventricles in patients with COPD, depending on the risk groups (A, B, C, D); to determine the possible directions of pharmacological correction.Methods. Patients (n = 119, including 87 men, mean age - 62.5 ± 14.8 years) with COPD of risk group A (n = 21) and B (n = 98) (GOLD, 2019). In addition to the routine clinical and instrumental examinations, pulmonary and aortic pulse wave velocity was determined using MRI diagnostics.Results. The right ventricular diastolic dysfunctions (DD) were revealed in all patients with COPD (E/A TV = 0.85 ± 0,03 vs 0.97 ± 0,03; groups A and B respectively, p < 0,05). 28.6% of patients of group B had a restrictive type of transtricuspid blood flow (p < 0,05). The pulmonary blood pressure was increased: 24.3 ± 7.6 mm Hg in patients with COPD group A, 17.2 ± 6.8 mm Hg - in group B. Patients of group B had a higher pulmonary pulse wave velocity (pPWV) (B: 3.13 [2.93-3.44] ms-1 vs A: 1.97 [1.62-2.68] ms-1, p = 0.005) and stroke volume of RV (B: 33.5 [27.3-37.9] mL vs A: 29.1 [24.0-35.7] mL, p = 0.005). The correlation between pPWV and the degree of bronchial obstruction, ejection fraction and end-diastolic volume of the RV, and mean pulmonary arterial pressure (mPAP) was strong for patients of group B and moderate for patients of group A.Conclusion. Thus, patients with COPD risk group A have the borderline indicators of mPAP with DD of LV and RV. The progression of hemodynamic disorders is associated with the aggravation of of clinical symptoms and respiratory disorders, that were more pronounced in group B. This progression led to mandatory broncholytic drug correction.Целью работы явилась оценка легочной гемодинамики и наличия систолической и / или диастолической дисфункции (ДД) миокарда правого (ПЖ) и левого (ЛЖ) желудочков у больных хронической обструктивной болезнью легких (ХОБЛ) в зависимости от принадлежности к одной из групп риска (ABCD) согласно классификации Глобальной стратегии диагностики, лечения и профилактики ХОБЛ (Global Initiative for Chronic Obstructive Lung Disease — GOLD, 2019) а также определение возможных направлений медикаментозной коррекции.Материалы и методы. Обследованы больные ХОБЛ (n = 119, 87 мужчин; средний возраст - 62,5 ± 14,8 года) групп риска А (n = 21) и В (n = 98) по GOLD (2019). Помимо общепринятых клинико-инструментальных обследований, проводилось определение аортальной и легочной скорости распространения пульсовой волны (лСРПВ) с применением магнитно-резонансной томографии.Результаты. У всех больных ХОБЛ выявлены нарушения в виде ДД ПЖ (отношение максимальной скорости раннего диастолического наполнения к максимальной скорости предсердного диастолического наполнения (Е / АПЖ) у пациентов группы риска А составило 0,85 ± 0,03 vs 0,97 ± 0,03 - у пациентов группы риска В;р < 0,05). У 28,6 % больных группы риска В (р < 0,05) определялся рестриктивный тип транстрикуспидального кровотока. Легочная гипертензия у больных ХОБЛ группы риска А составила 24,3 ± 7,6 мм рт. ст., группы риска В - 17,2 ± 6,8 мм рт. ст. У пациентов группы риска В отмечены более высокие значения лСРПВ (3,13 (2,93-3,44) мс-1 vs 1,97 (1,62-2,68) мс-1 у пациентов группы риска A; р = 0,005) и ударного объема ПЖ (33,5 (27,3-37,9) мл у пациентов группы риска В vs 29,1 (24,0-35,7) мл - у пациентов группы риска А; р = 0,005). Установлена сильная корреляция показателей лСРПВ со степенью бронхиальной обструкции, фракции выброса и конечного диастолического объема ПЖ, среднего давления в легочной артерии (ДЛАср.) у больных группы В и умеренной силы корреляция - у пациентов группы риска А.Заключение. Таким образом, у больных ХОБЛ группы риска А по GOLD (2019) определяются пограничные показатели ДЛАср. с развитием ДД ПЖ и ЛЖ. Прогрессирование гемодинамических нарушений связано с утяжелением клинических проявлений и дыхательных расстройств, более выраженных у пациентов группы риска В, при этом требуется обязательная бронхолитическая медикаментозная коррекция