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Traditional Chinese medicine has been proven to be of great significance in cardioprotective effects. Clinopodium chinense (Lamiaceae) has unique advantages in the treatment and prevention of cardiovascular diseases. Tournefolic acid B (TAB) was proven to be a potent component against myocardial ischemia reperfusion injury (MIRI) from Clinopodium chinense (Lamiaceae). This article will attempt to establish a gram-scale synthesis method of TAB and discuss the structure-activity relationship of its analogs. The total synthesis of TAB was completed in 10 steps with an overall yield of 13%. In addition, analogs were synthesized, and their cardioprotective activity was evaluated on the hypoxia/reoxygenation of H9c2 cells. Amidation of the acid position is helpful to the activity, while methylation of phenolic hydroxyl groups greatly decreased the cardioprotective activity. The easily prepared azxepin analogs also showed cardioprotective activity. Most of the clogP values calculated by Molinspiration ranged from 2.5 to 5, which is in accordance with Lipinski’s rule of 5. These findings represent a novel kind of cardioprotective agent that is worthy of further study.

Renal sodium-glucose cotransporter‑2 (SGLT2) inhibitors seem to have a cardioprotective effect beyond the antidiabetic effect. The underlying mechanisms are unclear.Selective search in PubMed with a focus on heart failure endpoints and possible mechanisms of action.During treatment with three of the substances analyzed, there were fewer hospitalizations for heart failure compared with placebo; however, the numbers needed to treat within the primary analyses were relatively high (72-117). We found that loss of weight and lowering of blood pressure were more pronounced during treatment with verum than with placebo and an association of the preventive effect with more severely impaired renal function.The SGLT2 inhibitors show a moderate heart failure protective effect in diabetic patients. It is likely that a nephroprotective effect with modulation of the cardiorenal interaction is an important part of the mechanism of action but this must be substantiated in further investigations.HINTERGRUND: Hemmstoffe des renalen Natrium-Glukose-Kotransporters 2 („sodium glucose-linked transporter 2“; SGLT2i) scheinen außer der antidiabetischen auch eine kardioprotektive Wirkung zu besitzen; deren Mechanismus ist jedoch unklar.Selektive Literaturrecherche in PubMed (Fokus Herzinsuffizienz und Wirkmechanismen).Unter Therapie mit 3 der untersuchten Substanzen kam es im Vergleich mit Placebo zu weniger herzinsuffizienzbedingten Krankenhausaufenthalten, allerdings mit einer relativ hohen Anzahl von Behandlungen pro verhindertes Ereignis (72–117). Außer einer stärkeren Gewichtsabnahme und Blutdrucksenkung unter dem Verum gegenüber Placebo fiel eine Zunahme des kardioprotektiven Effekts bei stärker eingeschränkter Nierenfunktion auf.Ein moderater herzinsuffizienzpräventiver Effekt von Hemmstoffen des renalen SGLT2 kann bei Diabetikern als gesichert gelten. Ein wesentlicher Wirkmechanismus beruht wahrscheinlich auf einem nephroprotektiven Effekt mit Modulation der kardiorenalen Interaktion, was jedoch weiterer Abklärung bedarf.

Schizandrol A (SA) is an bioactive component isolated from the Schisandra chinensis (Turcz.) Baill., which has been used as a remedy to prevent oxidative injury. However, whether the cardioprotective effect of SA is associated with regulating endogenous metabolites remains unclear, thus we performed comprehensive metabolomics profiling in acute myocardial ischemia (AMI) mice following SA treatment. AMI was induced in ICR mice by coronary artery ligation, then SA (6 mg·kg −1 ·d −1 , ip) was administered. SA treatment significantly decreased the infarct size, preserved the cardiac function, and improved the biochemical indicators and cardiac pathological alterations. Moreover, SA (10, 100 M) significantly decreased the apoptotic index in OGD-treated H8c2 cardiomycytes in vitro. By using HPLC-Q-TOF/MS, we conducted metabonomics analysis to screen the significantly changed endogenous metabolites and construct the network in both serum and urine. The results revealed that SA regulated the pathways of glycine, serine and threonine metabolism, lysine biosynthesis, pyrimidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, valine, leucine and isoleucine biosynthesis under the pathological conditions of AMI. Furthermore, we selected the regulatory enzymes related to heart disease, including ecto-5’-nucleotidase (NT5E), guanidinoacetate Nmethyltransferase (GAMT), platelet-derived endothelial cell growth factor (PD-ECGF) and methionine synthase (MTR), for validation. In addition, SA was found to facilitate PI3K/Akt activation and inhibit the expression of NOX2 in AMI mice and OGD-treated H9c2 cells. In conclusion, we have elucidated SA-regulated endogenous metabolic pathways and constructed a regulatory metabolic network map. Furthermore, we have validated the new potential therapeutic targets and underlying molecular mechanisms of SA against AMI, which might provide a reference for its future application in cardiovascular diseases.

Введение. Обеспечение анальгезии и наркоза с середины ХХ века осуществляется с использованием инертного газа ксенона, как самостоятельного фактора, так и совместно с другими способами воздействия. Изучен механизм его действия, получено разрешение на его применение в медицинских целях в России, а также в ряде стран Европы. Выявлено, что концентрации ксенона во вдыхаемой смеси от 25% до 50% обеспечивает анксиолитический и анальгетический эффекты, а концентрации более 60-70% обусловливают наркотический эффект и общую анестезию. Поскольку, в соответствии с Киотским протоколом, планируется к 2030 г. отказ от использования ингаляционных анестетиков, содержащих атомы фтора, углерода и хлора, ведутся поиски оптимального сочетания ксенона и других газов в медицине. Цель обзора дать характеристику технологий применения инертного газа ксенона в медицинских целях. Материалы и методы. В обзоре использованы результаты исследований российских ученых, в том числе материалы полученных патентов, опубликованных в базе данных elibrary. Результаты и их обсуждение. Определены такие свойства ксенона, как экспериментально подтвержденные кардиопротекторный и нейропротекторный эффекты, обосновано их использование в клинической медицине, а также отсутствие нежелательных эффектов при его применении. Разработана диагностическая ксеноновая компьютерная томография и рентгеноскопия головного мозга, визуализирующие гемодинамику в головном мозге, что обеспечивает диагностику острого инсульта. Подтверждены противоинфекционное воздействие ксенона, его кардиопротективная способность, используемая в хирургии ишемической болезни сердца. Установлен его лечебный эффект при повреждениях головного мозга, при остановке сердечной деятельности, при послеоперационных осложнениях (делирии, сепсисе), панических атаках, при стрессах, физических перегрузках в спорте, лечении наркозависимости, при обезболивании в онкологии. Запатентован способ неингаляционного перорального введения клатратных соединений ксенона, в которых его молекулы расположены в пустотах кристаллической решетки льда, с локализацией в термоизолирующей капсуле. Заключение. Необходимы теоретические и экспериментальные исследования ксенона, установление детальных механизмов его воздействия на человека, поиск его оптимальных концентраций, сочетаний с другими факторами воздействия, в том числе и физическими, поиск и оптимизации способов его доставки во внутренние среды организма., Introduction. The provision of analgesia and anesthesia since the middle of the twentieth century has been carried out using the inert xenon gas, both as an independent factor and in conjunction with other methods of exposure. The mechanism of its action has been studied, a permission has been obtained for its use for medical purposes in Russia, as well as in a number of European countries. It was found that the concentration of xenon in the inhaled mixture from 25% to 50% provides anxiolytic and analgesic effects, and concentrations of more than 60-70% cause a narcotic effect and general anesthesia. In accordance with the Kyoto Protocol, by 2030 it is planned to abandon the use of inhalation anesthetics containing fluorine, carbon and chlorine atoms. Today, searches are underway for the optimal combination of xenon and other gases in medicine. The purpose of the review is to characterize the technologies for the use of xenon inert gas for medical purposes. Material and methods. The review uses the results of research by Russian scientists, including materials obtained by patents published in the elibrary database. Results. Such properties of xenon as experimentally confirmed cardioprotective and neuroprotective effects are determined. Their use in clinical medicine is justified, as well as the absence of undesirable effects in its application. Diagnostic xenon computed tomography and fluoroscopy of the brain have been developed that visualize hemodynamics in the brain, which provides the diagnosis of acute stroke. Anti-infective effects of xenon, its cardioprotective ability, used in surgery for coronary heart disease are confirmed. Its therapeutic effect has been established for brain damage, cardiac arrest, postoperative complications (delirium, sepsis), panic attacks, stress, physical overload in sports, drug addiction treatment, pain relief in oncology. A method of non-inhalation oral administration of xenon clathrate compounds, in which its molecules are located in the voids of the ice crystal lattice, with localization in a thermally insulating capsule, has been patented. Conclusion. It is necessary to conduct theoretical and experimental studies of xenon, to establish the detailed mechanisms of its effect on humans, to search for its optimal concentrations, combinations with other factors of influence, including physical ones, to search for and optimization of ways to deliver it to the internal environment of the body.

Macaíba pulp (Acrocomia intumescens Drude) contains unsaturated fatty acids, in addition to antioxidants, which makes it a consumption option for individuals who practice physical exercise. Thus, the objective of this research was to verify the effects of the consumption of Macaíba pulp on physical, biochemical, oxidative and behavioral stress parameters in exercised rats. For this purpose, 44 rats were used, divided into four groups, with a number of 11 animals each, as follows: sedentary control (CT), sedentary macaw (MC), exercised control (CT-EX) and exercised macaw (MC- EX). The CT and CT-EX groups received, by gavage, distilled water, while MC and MC-EX received, by gavage, macaiba pulp at a concentration of 1000 mg/kg of animal weight. All animals received commercial feed ad labitum. The animals in the CT-EX and MC EX groups were submitted to the exercise protocol, which consisted of a swimming period (free swimming), for a period of eight weeks. In the first week of training, adaptation phase, in which the exercise time followed ascending order, starting with 10 min and daily adding 10 min. At the end of the treatment, all animals were submitted to behavioral tests, using the open field (AC), elevated plus maze (LCE) and light-dark box (CCE) apparatus to verify anxiety parameters. Forty-eight hours after the behavioral tests, the animals were euthanized and the physical parameters were checked, and with the blood collected, biochemical parameters were quantified. With the values of lipoproteins, the cardiovascular risk was verified. The liver was removed and the concentration of malonaldehyde (MDA), total fat, total cholesterol (TC), triglycerides (TG) and histology were evaluated. Heart tissue was removed and MDA quantified. It was considered statistically different when p < 0.05. From the data obtained, it was found that sedentary and exercised animals that consumed Macaíba pulp presented reduced anxiety, with a greater number of ambulation and rearing and shorter grooming time in the CA, they also had a greater number of entries and time spent in open arms, greater number of head dives and less time in closed arms in the CSF. MC-EX still presented a greater number of entries and permanence in the clear part of the CCE. As for the physical parameters evaluated, we found that both MC and MC-EX showed a reduction in weight, with this reduction being more expressive for MC-EX. MC and MC-EX showed a reduction in body fat (mesenteric, retroperitoneal and epididymal), low and very low density lipoproteins, CT, aspartate and alanine aminotransferase, cholesterol, MDA in the heart, in addition to reduced coronary and cardiovascular risks. We still found an increase in HDL in MC and MC-EX. Thus, concluding that the consumption of Macaíba pulp induced anxiolytic, cardioprotective effect, modulated biochemical parameters, in addition to contributing to the reduction of visceral fat. Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES A polpa de macaíba (Acrocomia intumescens Drude) contém ácidos graxos insaturados, além de antioxidantes, o que a torna uma opção de consumo para indivíduos praticantes de exercício físico. Desta forma, objetivou-se com esta pesquisa verificar os efeitos do consumo da polpa de macaíba sobre os parâmetros físicos, bioquímicos, estresse oxidativo e comportamental em ratos exercitados. Para tanto, foram utilizados 44 ratos, sendo estes divididos em quatro grupos, com um número de 11 animais cada, sendo: controle sedentário (CT), macaíba sedentário (MC), controle exercitado (CT-EX) e macaíba exercitado (MC-EX). Os grupos CT e CT-EX receberam, por gavagem, água destilada, enquanto MC e MC-EX, receberam, por gavagem, polpa de macaíba na concentração de 1000 mg/kg de peso do animal. Todos os animais receberam ração comercial ad labitum. Os animais dos grupos CT EX e MC-EX, foram submetidos ao protocolo de exercício, que consistia em um período de natação (nado livre), por um período de oito semanas. Na primeira semana de treinamento, fase de adaptação, em que o tempo do exercício seguiu ordem crescente, iniciando com 10 min e diariamente acrescentando 10 min. Ao final do tratamento, todos os animais foram submetidos a testes comportamentais, sendo usados os aparatos do campo aberto (CA), labirinto em cruz elevado (LCE) e caixa claro-escuro (CCE), para verificação de parâmetros de ansiedade. Quarenta e oito horas após os testes comportamentais os animais foram eutanasiados e realizada aferição dos parâmetros físicos e com o sangue coletado foram quantificados parâmetros bioquímicos. Com os valores das lipoproteínas verificou-se o risco cardiovascular. O fígado foi retirado e avaliou-se a concentração de malonaldeído (MDA), gordura total, colesterol total (TC), triglicerídios (TG) e histologia. O tecido do coração foi retirado e quantificado o MDA. Foi considerado estatisticamente diferente quando p < 0,05. A partir dos dados obtidos, verificou-se que os animais que consumiram polpa de macaíba, sedentários e exercitados, apresentaram redução de ansiedade, com maior número de ambulação e de rearing e menor tempo de grooming no CA, eles também apresentaram maior número de entradas e tempo de permanência nos braços abertos, maior número de mergulhos de cabeça e menor tempo nos braços fechados no LCE. MC-EX ainda apresentou maior número de entradas e permanência na parte claro do CCE. Quanto aos parâmetros físicos avaliados, verificamos que tanto MC quanto MC-EX apresentaram redução de peso, sendo esta redução mais expressiva para MC-EX. MC e MC-EX apresentaram redução de gordura corporal (mesentérica, retroperitoneal e epididimal), de lipoproteínas de baixa e muito baixa densidade, TC, aspartato e alanina aminotransferase, colesterol, MDA no coração, além de redução riscos coronários e cardiovasculares. Ainda verificamos aumento de HDL em MC e MC-EX. Concluindo desta forma que o consumo da polpa de macaíba induziu efeito ansiolítico, cardioprotetor, modulou parâmetros bioquímicos, além de contribuir na redução de gorduras viscerais.

BmooMPα-I has kininogenase activity, cleaving kininogen releasing bradykinin and can hydrolyze angiotensin I at post-proline and aspartic acid positions, generating an inactive peptide. We evaluated the antihypertensive activity of BmooMPα-I in a model of two-kidney, one-clip (2K1C). Wistar rats were divided into groups: Sham, who underwent sham surgery, and 2K1C, who suffered stenosis of the right renal artery. In the second week of hypertension, we started treatment (Vehicle, BmooMPα-I and Losartan) for two weeks. We performed an electrocardiogram and blood and heart collection in the fourth week of hypertension. The 2K1C BmooMPα-I showed a reduction in blood pressure (systolic pressure: 131 ± 2 mmHg; diastolic pressure: 84 ± 2 mmHg versus 174 ± 3 mmHg; 97 ± 4 mmHg, 2K1C Vehicle, p < 0.05), improvement in electrocardiographic parameters (Heart Rate: 297 ± 4 bpm; QRS: 42 ± 0.1 ms; QT: 92 ± 1 ms versus 332 ± 6 bpm; 48 ± 0.2 ms; 122 ± 1 ms, 2K1C Vehicle, p < 0.05), without changing the hematological profile (platelets: 758 ± 67; leukocytes: 3980 ± 326 versus 758 ± 75; 4400 ± 800, 2K1C Vehicle, p > 0.05), with reversal of hypertrophy (left ventricular area: 12.1 ± 0.3; left ventricle wall thickness: 2.5 ± 0.2; septum wall thickness: 2.3 ± 0.06 versus 10.5 ± 0.3; 2.7 ± 0.2; 2.5 ± 0.04, 2K1C Vehicle, p < 0.05) and fibrosis (3.9 ± 0.2 versus 7.4 ± 0.7, 2K1C Vehicle, p < 0.05). We concluded that BmooMPα-I improved blood pressure levels and cardiac remodeling, having a cardioprotective effect.

The functional integrity of the endothelium is essential for vascular health. In addition to maintaining a delicate balance between vasodilation and vasoconstriction, the endothelium has numerous other complex roles involved in the maintenance of vascular homeostasis. Chronic exposure to cardiovascular risk factors and oxidative stress results in an imbalance in these functions, creating an environment that favors reduced vasodilation and a proinflammatory and prothrombic state. The involvement of endothelial dysfunction in all stages of the cardiovascular continuum makes it an important target for treatment. One of the major endothelial-derived factors involved in the maintenance of endothelial function is nitric oxide (NO). Angiotensin-converting enzyme (ACE) inhibitors increase NO production both directly and indirectly by preventing production of angiotensin II (which diminishes NO production) and inhibiting the degradation of bradykinin (which stimulates local release of NO). Among the ACE inhibitors, perindopril appears to have the greatest effects on bradykinin and has demonstrated efficacy in a number of markers of endothelial dysfunction including arterial stiffness and progression of atherosclerosis. There is also strong evidence supporting the use of perindopril-based therapy for the treatment of hypertension and for reducing the risk of cardiovascular morbidity and mortality in a wide range of patients across the cardiovascular continuum. Funding: The journal’s Rapid Service Fee was funded by Servier.

Background: Myocardial infarction (MI) is one of the most important causes of death worldwide. The effect of flunixin meglumine (FM) on MI is unknown. We investigated the protective effect of FM on the serum biochemical profile, malondialdehyde (MDA), and heart histology changes induced by isoproterenol (ISO) in adult male rats. Methods: Rats were randomly divided into four groups of six each as follows: Group 1, control. Group 2, was administered ISO subcutaneously at 85 mg/kg for 2 days. Group 3 was administered FM intraperitoneally at 2 mg/kg/d, for 3 days; and Group 4 was administered FM 2mg/kg/d intraperitoneally for 3 days and ISO 85mg/kg subcutaneously for two consecutive days. Blood samples were collected after anesthesia, 24h after the second ISO administration. The heart tissue was immediately removed for histopathological examination. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), Blood urea nitrogen (BUN), creatinine and serum MDA levels were measured on an autoanalyzer and spectrophotometer. Results: In Group 4 (FM+ISO) the levels of AST, LDH and MDA decreased compared with those for Group 2 (ISO) (P< 0.05). Histopathologic tests revealed that ISO induced myocardial injury in Group 3 rats, whereas the alterations of the heart architecture were improved by FM in Group 4 (FM+ISO). Conclusions: The results suggest that FM has a potential cardioprotective effect against an experimental model of MI in rats.

This investigation was aimed to explore the cardioprotective effect of Ramontchi fruits (Flacourtia indica; FI) in isoprenaline-administered Long-Evans rats. Administration of isoprenaline increased the total heart wet weight, MDA, NO, and APOP as well as ALT, AST, and CK-MB levels, which were normalized by FI fruits treatment. Moreover, expressions of antioxidant genes i.e., Nrf-2, HO-1, HO-2, SOD, catalase, and GPx were normalized by FI fruits in isoprenaline-induced rats. Besides, expression of inflammatory mediators i.e., IL-1, IL-6, TNF-α, TGF-β, iNOS, and NF-κB were also suppressed by FI fruits. The outcome of FI fruits treatment was noted as promising and comparable to the standard atenolol treatment. The enhanced biological activity shown by FI fruits may be due to its abundant polyphenolic compounds as determined by HPLC analysis. In conclusion, FI fruits may protect cardiac tissue in isoprenaline-administered rats by suppressing the oxidative stress and proinflammatory mediators and enhancing the antioxidant enzyme functions.

Background: Depression and coronary heart disease (CHD) often occur together in clinical practice. As a traditional Chinese medicine, Kai Xin San (KXS) has been widely used for the treatment of emotion related disorders. In the present study, we aimed to explore whether KXS had both antidepressive effects and cardioprotective functions in a rat model of myocardial ischemia (MI) with depression. Methods: A total of 50 SD rats were randomly assigned into five groups as follows: normal control (control group), celiac injection of isopropyl adrenaline (ISO) (MI group), depression (depression group), MI+ depression (model group) and MI+ depression treated with intragastric administration of 370 mg/kg KXS (KXS group). MI was induced by subcutaneous injection of 85 mg/kg ISO. Depression was developed by a 7-week chronic mild stress (CMS) challenge. Behavioral test was conducted before and during the experiment. Echocardiography and biochemical analysis were carried out after 7 weeks of CMS challenge. Results: After 7 weeks of experiment, depression-like behaviors were observed in all the groups except for control and KXS groups, and KXS treatment dramatically increased open-field test scores and sucrose consumption (P

In this study, we investigated the effects of isorhamnetin on myocardial ischaemia reperfusion (I/R) injury in Langendorff‐perfused rat hearts. Isorhamnetin treatment (5, 10 and 20 μg/mL) significantly alleviated cardiac morphological injury, reduced myocardial infarct size, decreased the levels of marker enzymes (LDH and CK) and improved the haemodynamic parameters, reflected by the elevated levels of the left ventricular developed pressure (LVDP), coronary flow (CF) and the maximum up/down velocity of left ventricular pressure (+dp/dtmax). Moreover, isorhamnetin reperfusion inhibited apoptosis of cardiomyocytes in the rats subjected to cardiac I/R in a dose‐dependent manner concomitant with decreased protein expression of Bax and cleaved‐caspase‐3, as well as increased protein expression of Bcl‐2. In addition, I/R‐induced oxidative stress was manifestly mitigated by isorhamnetin treatment, as showed by the decreased malondialdehyde (MDA) level and increased antioxidant enzymes activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‐Px). These results indicated that isorhamnetin exerts a protective effect against I/R‐induced myocardial injury through the attenuation of apoptosis and oxidative stress.

Amaç: Adipokinler pek çok aracı mediyatörlerle vücutta pek çok fonksiyonda düzenleyici rol oynamaktadır. Adipokinlere ilgi son yıllarda giderek artmaktadır. Günümüzde adipokinler birçok sistemik hastalıkta geleceğin potansiyel ilaç hedefleri olarak araştırılmaktadır. Bu tez çalışması ile amacımız metabolik yollarda önemli düzenleyici roller üstlenen adipokinlerin hipertansiyon patofizyolojisinde etkilerinin ortaya konması , hasta ve kontrol kan numunelerindeki çeşitli biyolojik parametreler ile ilişkilerinin araştırılmasıdır. Materyal-Metot Tez çalışmamız Dicle Üniversitesi Tıp Fakültesi Hastanesinde yapılmıştır. Vaka kontrol tipteki bu çalışmamızın evrenini 01.03.2019-01.09.2019 tarihleri arasında Dicle Üniversitesi Tıp Fakültesi Hastanesi Aile Hekimliği ve Kardiyoloji polikliniklerine başvuran 18 yaş üstü hastalar oluşturmuştur. Bulgular Çalışmamıza 96 sı hasta 84 ü kontrol grubundan olmak üzere toplam 180 kişi katıldı. Bunların 105 i kadın, 75 i erkek di. Hasta ve kontrol grubunda sistolik, diastolik tansiyon değerleri sırasıyla; 149,07± 15,689, 112,53 ± 10,064. Adipokinlerden hasta ve kontrol grupları için medyan ( min-max) sırayla leptin 7,84(1,13-980,88), 2,40(1,15- 46,92) (P< 0,001), visceral 1,01( 0,23-5,14), 0,79(0,1-2,65) (P=0,41), intellectin 74,18(10,3-1438,78), 37,53(10,1-131,54) (P< 0,001),chemerin 198,57(91,72-1380,13), 177,57(131,46-852,25) (P=0,347), Retinol binding protein 109,64(44,97-5314,66), 48,53(12,56-377,05) (P< 0,001) , adiponektin 5,21(1,08-23,90), 4,07(1,01-10,19) (P=0,016) , rezistin 529,32(119,97-3071,44), 276,18(109,24-1078,04) (P

High-density lipoprotein cholesterol (HDL-C) has been identified as a powerful independent negative predictor of cardiovascular disease. The beneficial effect of HDL is largely attributable to its key role in reverse cholesterol transport, whereby excess cholesterol in the peripheral tissues is transported to the liver, reducing the atherosclerotic burden. However, mounting evidence indicates that HDL also has pleiotropic properties, such as anti-inflammatory, anti-oxidative, and vasodilatory properties, which may contribute in reducing the incidence of heart failure. Actually, previous data from clinical and experimental studies have suggested that HDL exerts cardioprotective effects irrespective of the presence/absence of coronary artery disease. This review summarizes the currently available evidence regarding beneficial effects of HDL on the heart beyond its anti-atherogenic property. Understanding the mechanisms of cardiac protection by HDL will provide new insight into the underlying mechanism and therapeutic strategy for heart failure.

Obesity is a multifactorial chronic disease characterized by high body fat accumulation and a chronic proinflammatory state associated with other disorders such as glucose intolerance, dyslipidemias, hepatic steatosis, increased production of reactive oxygen species (ROS) and oxidative stress, and high cardiovascular risk, especially endothelial dysfunction, platelet aggregation, and hypertension. Hypercaloric diets have been widely used to induce obesity and metabolic complications in experimental studies, and thus allow the study of new strategies for the treatment of numerous chronic diseases. Thus, carboxymethyl glucan (CMG), a semisynthetic derivative of Saccharomyces cerevisiae β (1 → 3) (1 → 6) glucan, has been of interest for its immunostimulant effects and high antioxidant capacity. Thus, the study evaluated the effects of CMG on metabolic and cardiovascular changes induced by the consumption of hypercaloric diet in rats. The Animal Use Ethics Committee approved all experimental protocols of UFPB (CEUA 074/2017). Wistar rats were divided into three groups, NCT: normal caloric control; HCT: hypercaloric control; H-CMG: hypercaloric + CMG, the first received standard diet and saline solution, and the last two received hypercaloric diet, the last group being supplemented with CMG at a dose of 20 mg/kg/ day for 12 weeks. Weight and food intake data were evaluated throughout the experimental period. Glucose tolerance and systolic blood pressure (SBP) levels were evaluated in the last week and last day of the experiment, respectively. At the end of the study, dietary and morphometric parameters, fasting blood glucose, lipid profile, inflammation, and histology were analyzed, as well as platelet aggregation, oxidative stress, and vascular reactivity levels. Statistical tests were used to verify significant differences between groups (p

Oxidative stress plays an important role in the pathogenesis of myocardial infarction (MI). Schisandra chinensis bee pollen extract (SCBPE) possesses powerful antioxidant capacity. This study aimed to further explore the antioxidative and cardioprotective effects of SCBPE on acute MI induced by isoprenaline (ISO) in rats. The rats were intragastrically administrated with SCBPE (600, 1200, or 1800 mg/kg/day) and Compound Danshen dropping pills (270 mg/kg/day) for 30 days, then subcutaneously injected with ISO (65 mg/kg/day) on the 29th and 30th day. Compared with the model group, pretreatment with middle and high doses of SCBPE significantly reduced serum aspartate transaminase, lactate dehydrogenase, and creatine kinase activities and increased myocardial superoxide dismutase, glutathione peroxidase, and catalase activities. The histopathologic aspects showed that pathological heart change was found in the model group and reduced to varying degrees in the SCBPE groups. Moreover, the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), and Bcl2 in the heart increased in the SCBPE groups, while that of Bax decreased compared to the model group. Besides this, uridine was isolated from S. chinensis bee pollen for the first time. This study could provide a scientific basis for using Schisandra chinensis bee pollen as a functional food for the prevention of MI.

Doxorubicin, an anthracycline from Streptomyces peucetius, exhibits antitumor activity against various cancers. However, doxorubicin is cardiotoxic at cumulative doses, causing increases in intracellular reactive oxygen species in the heart. Spinochrome D (SpD) has a structure of 2,3,5,6,8-pentahydroxy-1,4-naphthoquinone and is a structural analogue of well-known sea urchin pigment echinochrome A. We previously reported that echinochrome A is cardioprotective against doxorubicin toxicity. In the present study, we assessed the cardioprotective effects of SpD against doxorubicin and determined the underlying mechanism. 1H-NMR-based metabolomics and mass spectrometry-based proteomics were utilized to characterize the metabolites and proteins induced by SpD in a human cardiomyocyte cell line (AC16) and human breast cancer cell line (MCF-7). Multivariate analyses identified 12 discriminating metabolites (variable importance in projection &gt, 1.0) and 1814 proteins from SpD-treated AC16 cells. Proteomics and metabolomics analyses showed that glutathione metabolism was significantly influenced by SpD treatment in AC16 cells. SpD treatment increased ATP production and the oxygen consumption rate in D-galactose-treated AC16 cells. SpD protected AC16 cells from doxorubicin cytotoxicity, but it did not affect the anticancer properties. With SpD treatment, the mitochondrial membrane potential and mitochondrial calcium localization were significantly different between cardiomyocytes and cancer cell lines. Our findings suggest that SpD could be cardioprotective against the cytotoxicity of doxorubicin.

All of the following traditional agents for the management of stable angina pectoris include the symptomatic treatment with heart rate-lowering agents such as β-blockers or non-dihydropyridine Ca-channel blockers, or ivabradine-the first selective sinus node If channel inhibitor-vasodilatators and preventive use of angiotensin-converting enzyme inhibitors affect the parameters of circulation directly. Trimetazidine exerts its anti-ischemic action by modulating cardiac metabolism without altering the hemodynamic functions, therefore represents an excellent complementary potential to the conventional angina treatment. It has a beneficial effect on the inflammatory profile and endothelial function and shows diverse benefits by reducing the number and the intensity of angina attacks and improving the clinical signs and symptoms of myocardial ischemia given as monotherapy as well as combined with other antianginal agents. Patients undergoing coronary revascularization procedures or with comorbid left ventricular dysfunction and diabetes mellitus also benefit from the protective effects of trimetazidine.

Objective(s): Paclitaxel is a potent chemotherapy agent with severe side effects, including allergic reactions, cardiovascular problems, complete hair loss, joint and muscle pain, which may limit its use and lower its efficiency. The cardioprotective effect of royal jelly was investigated on paclitaxel-induced damages. Materials and Methods: Adult male Wistar rats were divided into control and test groups (n=8). The test group was assigned into five subgroups; 4 groups, along with paclitaxel administration (7.5 mg/kg BW, weekly), received various doses of royal jelly (50, 100, and 150 mg/kg BW) for 28 consecutive days. The last group received only royal jelly at 100 mg/kg. In addition to oxidative and nitrosative stress biomarkers, the creatine kinase (CK-BM) level was also determined. To show the cardioprotective effect of royal jelly on paclitaxel-induced damages, histopathological examinations were conducted. Results: Royal jelly lowered the paclitaxel-elevated malondialdehyde and nitric oxide levels in the heart. Royal jelly could also remarkably reduce the paclitaxel-induced cardiac biomarker of creatine kinase (CK-BM) level and pathological injuries such as diffused edema, hemorrhage, congestion, hyaline exudates, and necrosis. Moreover, royal jelly administration in a dose-dependent manner resulted in a significant (P

Necrosis of the myocardium due to imbalance between coronary blood supply and oxygen demand of the myocardial tissue promotes the evolution of acute myocardial infarction (MI). Onions are considered a rich source of medicinal compounds, of which cycloalliin (CYC), a sulfur containing imino compound with a cyclic structure, has been been extensively reported to exhibit various pharmacological activities. The present study aimed to elucidate the protective effect of cycloalliin in isoproternol (ISO)-induced myocardial infarction in male albino Wistar rats. Results of our investigation showed that treatment with CYC (10 mg/kg) significantly elevated both (+) and (−) left ventricular delta pressure/delta time (LVdP/dt) and decreased left ventricular end diastolic pressure LVEDP compared to the isoproterenol-treated group. The level of TBARS was significantly increased in the ISO-treated group. This was accompanied by diminished myocardial creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities when compared with the control group (p

The study aimed to investigate the nephroprotective and cardioprotective effects of ethanol extract of litchi leaf (LI) in two-kidney-one-clip (2K1C) rat model. HPLC analysis revealed the presence of several polyphenolic antioxidants in LI. Correspondingly, LI at 50–200 mg/kg reduced the level of oxidative stress markers (MDA, APOP, NO) and improved level of endogenous antioxidant enzymes (CAT, SOD) in 2K1C rats. Besides, LI caused significant improvements in kidney and heart functions in 2K1C rats by reducing the plasma level of uric acid and creatinine as well as CK-MB. Consistent with the biochemical findings, histopathological data further confirmed that LI is effective in decreasing heart and kidney injuries, oxidative stress and inflammation which ensued in 2K1C rats. Collectively, the outcomes suggest that the LI enriched in polyphenolic antioxidants may provide the protection against excessive oxidative stress, inflammation and tissue injury, thereby improving the kidney and heart function in 2K1C rats.

Background Er-Xian decoction (EXD), a formula of Chinese medicine, is often used to treat menopausal syndrome in China. The aim of the present study was to explore the potential cardioprotective mechanism of EXD against myocardial injury in an ovariectomy-induced menopausal rat model. Methods We divided the female Wistar rats into ovariectomy group and sham operation group (SHAM group). The ovariectomized (OVX) rats received treatment of vehicle (OVX group), EXD (EXD group) or 17β-estradiol (E2 group). After 12-week of treatment, the level of estradiol in serum was detected using an electrochemiluminescence immunoassay, and electrophysiologic changes in myocardial action potentials (AP) were evaluated using intracellular microelectrode technique. Changes in the histopathology of the left ventricle and the ultrastructure of the cardiomyocytes were observed by hematoxylin and eosin (HE) staining and transmission electronmicroscopy to assess myocardial injury. Microarrays were applied for the evaluation of gene expression profiles in ventricular muscle of the OVX and EXD rats. Further pathway analyses of the differential expression genes were carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG). And real-time quantitative RT-PCR (qRT-PCR) was used for verification of the key findings. Results The results from electrophysiological and histomorphological observations demonstrated that EXD had a substantial myocardial protective effect. The EXD-treated rats, in comparison with the OVX rats, demonstrated up-regulated expression of 28 genes yet down-regulated expression of 157 genes in the ventricular muscle. The qRT-PCR assay validated all selected differential expression genes. The KEGG pathway analysis showed that the down-regulated genes were relevant to cardiomyopathy and myocardial contractility. EXD could decrease the mRNA expressions of cardiac myosin (Myh7, Myl2) and integrin (Itgb5) in the ventricular myocardium. Conclusion EXD had a protective effect against myocardial injury in OVX rats, and this cardioprotective effect may be associated with modulation of the expression of cardiac myosin or integrin at the mRNA level. Electronic supplementary material The online version of this article (10.1186/s12906-018-2311-9) contains supplementary material, which is available to authorized users.

Modulation of posttranslational modifications (PTMs), such as protein acetylation, is considered a novel therapeutic strategy to combat the development and progression of cardiovascular diseases. Protein hyperacetylation is associated with the development of numerous cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction. Several phytochemicals exert cardioprotective effects by regulating protein acetylation levels. These effects are mainly exerted via activation of Sirt1 and Sirt3 and inhibition of acetyltransferases. Numerous studies support a cardioprotective role for sirtuin activators (e.g., resveratrol), as well as other emerging modulators of protein acetylation, including curcumin, honokiol, oroxilyn A, quercetin, epigallocatechin-3-gallate, bakuchiol, tyrosol, and berberine. Studies also point to a cardioprotective role for various nonaromatic molecules, such as docosahexaenoic acid, alpha-lipoic acid, sulforaphane, and caffeic acid ethanolamide. Here, we review the vast evidence from the bench to the clinical setting for the potential cardioprotective roles of various phytochemicals in the modulation of sirtuin-mediated deacetylation. © 2017 Niria Treviño-Saldaña and Gerardo García-Rivas.

The aim of the study is to analyze the influence of combination of pyrimidine and 3-hydroxypyridine derivatives — xymedon and mexidol, in comparison with kardioxane on the myocardial bioelectric activity and arterial pressure level in rats with Walker-256 carcinoma at the doxorubicin and paclitaxel chemotherapy. Material and Methods. Experiments have been carried out on 100 Wistar female rats of weight of 150-250 grams. Doxorubicin and paclitaxel were administered intraperitoneally in a dosage of 4mg/kg and 6mg/kg respectively on the 11th day of experiment. Xymedon (100mg/kg) and mexidol (50mg/kg) were administered separately and in combination with each other, starting with the 11th day of experiment for 10 days. Kardioxane was injected in the dosage of 80mg/kg 20 min before cytostatics. We estimated a myocardial bioelectric activity and arterial pressure level changes on the 11th and 22d day of the experiment. The results. Xymedon and mexidol combination has limited the development of myocardial electrical instability comparable to kardioxane action. This combination has prevented the appearance of metabolic changes of ischemic genesis in the heart more efficiently than kardioxane. Xymedon and mexidol have normalized QT interval dispersion corrected by heart rate less efficiently than kardioxane. Conclusion. The combination of xymedon and mexidol has reduced cardiotoxicity of antitumor therapy more efficiently than the separated use of these medicines or the use of cardioxane.

Gilbert\'s syndrome (GS) is a benign condition that does not progress to chronic liver disease or fibrosis. GS diagnosis should be considered in patients with chronic elevation of unconjugated bilirubin. In these patients the presence of hemolysis and other diseases of the liver should be excluded. GS is an autosomal recessive disease. The mutation of UDP-glucuronyl transferase is seen in 10-16% of the population. There is a 70-80% decrease in bilirubin glucuronidation. In cases of unexplained indirect hyperbilirubinemia with no history of drugs, smoking or alcohol use, GS should be considered. Firstly, hemolysis should be excluded. It has been reported that having increased levels of indirect bilirubin lowers the incidence of carotid plaque and coronary artery disease in patients of GS. The antioxidation and resistance to oxidative stress status of patients with GS is known to be high. However, GS is associated with breast and colon cancer. Several studies have reported that liver transplantation from a patient with GS had no harm to himself or to the recipient. An exact relationship between schizophrenia and GS has not been demonstrated. GS patients have a risk of breast and colon cancer so frequent follow up may be recommended.

Objective: The study was conducted to evaluate cardioprotective effect of silk cocoon (Abresham) Bombyx mori (B. mori) on isoprenaline-induced myocardial infarction. This study deals with the cocoons, which is called Abresham in the Unani system of medicine. It is one of the 64 drugs which Avicenna has mentioned in Avicenna’s tract on cardiac drugs and used in the treatment of cardiovascular diseases. Abresham is a chief ingredient of the two very famous Unani formulation viz. Khamira Abresham Sada, and Khamira Abresham Hakim Arshad Wala. Materials and Methods: The ethanolic extract of B. mori (Abresham) silk cocoons in the dose of 250 mg/kg and 500 mg/kg body weight was administered orally for 28 days before isoprenaline administration to test their cardioprotective effect. Isoprenaline (85 mg/kg) was administered subcutaneously on days 29th and 30th, respectively in order to induce myocardial infarction. Results: The parameters for evaluation of cardioprotective activity were the physical parameters and the biochemical estimations. The physical parameters were gross examination of heart, heart weight/body weight ratio and histopathology examination. In biochemical estimations, the activity of various cardiac enzymes such as aspartate transaminase, alanine transaminase, creatinine kinase, lactate dehydrogenase, and the gold marker troponin-I were determined. The levels altered by isoproterenol were restored significantly by the administration of the both doses of test extract especially at higher dose. Conclusion: The result of this study shows that alcoholic extract B. mori has significant cardioprotective activity against isoprenaline-induced myocardial infarction.

Background Infusion of allogeneic cardiosphere‐derived cells (allo‐ CDC s) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long‐term effects of allo‐ CDC s have not been assessed. We performed a placebo‐controlled pivotal study for long‐term evaluation, as well as shorter‐term mechanistic studies. Methods and Results Minipigs underwent 1.5‐hour mid‐left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo‐ CDC s or vehicle 30 minutes postreperfusion. Left ventriculography ( LVG ) demonstrated preserved ejection fraction ( EF ) and attenuation of LV remodeling in CDC ‐treated pigs. Pigs underwent cardiac magnetic resonance imaging ( MRI ) and LVG 1 hour and 8 weeks after therapy to evaluate efficacy. MRI showed improvement of EF and attenuation of LV remodeling immediately after allo‐ CDC infusion. In addition, allo‐ CDC s improved regional function and decreased hypertrophy 2 months post‐treatment. Histological analysis revealed increased myocardial salvage index, enhanced vascularity, sustained reductions in infarct size/area at risk and scar transmurality, and attenuation of collagen deposition in the infarct zone of allo‐ CDC ‐treated pigs at 2 months. Allo‐ CDC s did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short‐term experiments designed to probe mechanism revealed antiapoptotic effects of allo‐ CDC s on cardiomyocytes and increases in cytoprotective macrophages, but no increase in overall inflammatory cell infiltration 2 hours after cell therapy. Conclusions Allo‐ CDC infusion postreperfusion is safe, improves cardiac function, and attenuates scar size and remodeling. The favorable effects persist for at least 2 months after therapy. Thus, cellular postconditioning confers not only acute cardioprotection, but also lasting structural and functional benefits.

Infusion of allogeneic cardiosphere-derived cells (allo-CDCs) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long-term effects of allo-CDCs have not been assessed. We performed a placebo-controlled pivotal study for long-term evaluation, as well as shorter-term mechanistic studies. Minipigs underwent 1.5-hour mid-left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo-CDCs or vehicle 30 minutes postreperfusion. Left ventriculography (LVG) demonstrated preserved ejection fraction (EF) and attenuation of LV remodeling in CDC-treated pigs. Pigs underwent cardiac magnetic resonance imaging (MRI) and LVG 1 hour and 8 weeks after therapy to evaluate efficacy. MRI showed improvement of EF and attenuation of LV remodeling immediately after allo-CDC infusion. In addition, allo-CDCs improved regional function and decreased hypertrophy 2 months post-treatment. Histological analysis revealed increased myocardial salvage index, enhanced vascularity, sustained reductions in infarct size/area at risk and scar transmurality, and attenuation of collagen deposition in the infarct zone of allo-CDC-treated pigs at 2 months. Allo-CDCs did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short-term experiments designed to probe mechanism revealed antiapoptotic effects of allo-CDCs on cardiomyocytes and increases in cytoprotective macrophages, but no increase in overall inflammatory cell infiltration 2 hours after cell therapy. Allo-CDC infusion postreperfusion is safe, improves cardiac function, and attenuates scar size and remodeling. The favorable effects persist for at least 2 months after therapy. Thus, cellular postconditioning confers not only acute cardioprotection, but also lasting structural and functional benefits.

Objective: To evaluate the cardioprotective potential of 70% ethanolic extract of bark of Spathodea campanulata P. Beauv (EEBSC). Methods: Wister strain rats were pretreated with EEBSC in two different doses (250 and 500mg/kg) orally for 14 d and then intoxicated with isoproterenol (200 mg/ kg, s.c. for 2 consecutive days at an interval of 24 h on 14th and 15th day of treatment protocol) to induce myocardial injury. Results: Cardioprotection was assessed by estimating serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine phosphokinase, triglycerides, total cholesterol, low density lipoproteins and high density lipoproteins. The levels of thiobarbituric acid reactive substances and reduced glutathione were analyzed in heart homogenate. In isoproterenol-treated group, shrinkage of cardiac markers in serum and elevated lipid peroxidation accompanied by decreased content of reduced glutathione in heart. The prior administration of EEBSC significantly (P

SummaryBackgroundThis study was designed to evaluate the factors that affect myocardial salvage after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).Methods and resultsOne hundred and eighty-three patients with AMI who had undergone successful PCI were recruited for this study. Patients underwent 99mTc-pyrophosphate single photon emission computed tomography (SPECT) on the third day and 99mTc-MIBI SPECT on the sixth day after admission. In the 20 SPECT segments, the summed defect score (TDS) and extent score (ES) of AMI segments were determined and the percentage of the salvaged myocardium was calculated based on the TDS and ES. We performed multivariate analysis to evaluate factors that can affect myocardial salvage. Multivariate analysis was performed among the value of myocardial salvage rate and the 15 clinical variables. Administration of nicorandil (p=0.006), prodromal angina (p

Background To evaluate the cardioprotective effects of sevoflurane versus propofol anesthesia in patients undergoing cardiac surgery. Methods Studies were retrieved through searching several databases. Study quality was evaluated by Jadad scale. Meta-analysis was performed with RevMan5.0 software. Publication bias was tested by funnel plot. Results As a result, 15 studies were included. Compared with propofol, sevoflurane anesthesia significantly improved postoperative (WMD (weighted mean difference) = 0.62, 95% CI: 0.33 to 0.92; P < 0.0001) and postoperative 12 hour cardiac index (WMD = 0.18, 95% CI: 0.03 to 0.33; P = 0.02), postoperative cardiac output (WMD = 1.14, 95% CI: 0.74 to 1.54; P < 0.00001), and reduced postoperative 24 hour cardiac troponin I concentration (WMD = -0.86, 95% CI:-1.49 to -0.22; P = 0.008), postoperative inotropic drug usage (OR (odds ratio) = 0.31, 95% CI: 0.22 to 0.44; P < 0.00001), vasoconstrictor drug usage (OR = 0.30, 95% CI:0.21 to 0.43; P < 0.00001), ICU stay (WMD = -15.53, 95% CI: -24.29 to -6.58; P = 0.0007) and a trial fibrillation incidence (OR = 0.25, 95% CI: 0.07 to 0.85; P = 0.03). However, no significant differences were found in other indexes. Subgroup analysis indicated the similar results. Discussion The sevoflurane-induced cTnI reduction is associated with lower incidence of late adverse cardiac events, accounting for its roles in cardiac protection. Several limitations existed such as the small sample size and the lack use of blind design. Conclusions Sevoflurane may exhibit a more favorable cardioprotective effect during cardiac surgery than propofol.

Salvia miltiorrhiza and ligustrazine are traditional Chinese medicines that have been used in combination for treatment of cardiovascular disease, including coronary heart disease, cardiac angina and atherosclerosis in Asia, in particular, China. The present study aimed to determine the effect of S. miltiorrhiza and ligustrazine injection (SLI) on myocardial ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) injuries via the Akt serine/threonine kinase (Akt)‑endothelial nitric oxide synthase (eNOS) signaling pathway. Male Sprague‑Dawley rats were randomly assigned into six groups: i) Sham group; ii) I/R group; iii) Low‑SLI group (6.8 mg/kg/day, i.p.); iv) Medium‑SLI group (20.4 mg/kg/day, i.p.); v) High‑SLI group (61.2 mg/kg/day, i.p.); vi) verapamil group (6 mg/kg/day, i.p.). Prior to surgery, the aforementioned groups were pretreated with a homologous drug once per day for 3 days. The effect of SLI following 35 min coronary artery occlusion and 2 h reperfusion was evaluated by determining infarct size, hemodynamics, biochemical values and histological observations. Additionally, cell viability, caspase‑3 expression, B cell leukemia/lymphoma‑2 (Bcl‑2)/Bcl‑2‑associated X protein (Bax) ratio, phosphorylated (p‑)Akt and p‑eNOS were also investigated following 2 h simulated ischemia and 2 h simulated reperfusion in H9C2 cardiomyocyte cells. Pretreatment with SLI significantly improved cardiac function in a dose‑dependent manner and reduced myocardial infarct size, creatine kinase, lactate dehydrogenase and malondialdehyde levels in blood serum. Additionally, myocardial histopathology changes in the rat model were also alleviated in SLI treatment groups. The present in vitro study revealed that treatment with SLI reduced the apoptotic rate of H9C2 cells by inhibiting the activation of caspase‑3 and increasing the Bcl‑2/Bax ratio. The effect of SLI was associated with increased phosphorylation of the survival kinase Akt at Ser473 and its downstream target eNOS following H/R. The present study determined that SLI may alleviate I/R injury in cardiomyocytes and inhibit apoptosis in rats by the activation of the Akt‑eNOS signaling pathway, and downregulation of the expression levels of proapoptotic factors, including caspase-3.

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In spite of achievements in the sphere of highly effective drugs creation for treating cardiovascular diseases the problem is still urgent since mortality is high because of these diseases, and it takes the 2-nd – 3-d place among the population of industrially developed countries. In the Research and Production Association “Pharmatron” a new approach concerning creation of new effective anti-anginal drugs has been developed; it is a chemical modification of position 1 and 4 of 1,2,4-triazole molecule by introduction of the structural fragments of the most active medicines and structures imitating sites of adrenergic receptors. Bromides of 1-(alkyl) carboxyalkyl-4-ylideneamino-1,2,4-triazole have been synthesized at the Pharmaceutical Chemistry department of Zaporizhzhia State Medical University under the supervision of professor I.A.Mazur. The cardioprotective activity of 12 compounds – derivatives of 1-carboxyalkyl-4-ylideneamino-1,2,4-triazole bromides and 1-alkyl-4-ylidenamino-1,2,4-triazole bromides has been investigated. The experiments were conducted in 510 white outbred male rats weighing 120-130 g from the mouse bank of the Institute of Pharmacology and Toxicology of the AMS of Ukraine. Determination of acute toxicity of the compounds investigated was conducted according to Kerber method. It has been found that LD50 of these compounds when introduced intraabdominally to rats is within 29.5-295 mg/kg. It allows to refer the compounds under research to the III and IV classes of toxicity (moderate or low toxic). The model of acute myocardial infarction in rats was used for studying the cardioprotective activity of the compounds, the infarction was modeled by staged introduction of isadrin and pituitrin. It has been found that intraabdominal introduction of 8 compounds of 12 ones in the dose of 1/100 LD50 to rats with myocardial infarction leads to decrease of hyperenzymemia of cardiospecific isoenzymes of creatine phosphokinase (MB CPK) and lactate dehydrogenase (LDH-1), which play the role of biochemical markers of the myocardium damage, and decrease of electrophysiological marker ΣΔST during electrocardiography. The structural fragments of the molecule, which play a determinative role in manifestation of the cardioprotective effect of such series as β-phenylethyl, carboxy propyl, octyl in position 1 and the presence of amino- and n-methoxybensilidenamino-groups in position 4, have been revealed. It has been determined that compound MT significantly exceeds the therapeutical efficacy of metoprolol by decrease of MB CPK and LDH-1 activity in the blood serum of rats with myocardial infarction, as well as decrease of ECG ST amplitude., Несмотря на достигнутые успехи в области создания высокоэффективных средств лечения сердечно-сосудистых заболеваний, проблема остается актуальной – смертность от этой патологии остается высокой и занимает 2-3 место среди населения промышленно развитых стран. В НПО «Фарматрон» было разработано новое направление по созданию новых эффективных антиангинальных средств, которое заключается в химической модификации 1 и 4 положения молекулы 1,2,4-триазола путем введения структурных фрагментов наиболее активных лекарственных препаратов, и структур, имитирующих сайты адренергических рецепторов. Были получены бромиды 1-(алкіл) карбоксиалкил-4-илиденамино-1,2,4-триазолия, синтезированные на кафедре фармацевтической химии ЗГМУ под руководством проф. И.А.Мазура. Была исследована кардиопротектинная активность 12 соединений производных бромидов 1-карбоксиалкил-4-илиденамино-1,2,4-триазол и бромидов 1-алкил-4-илиденамино-1,2,4-триазолия. Экспериментальную часть проводили на 510 белых беспородных крысах самцах массой 120-130 г, полученных из питомника Института фармакологии и токсикологии НАМН Украины. Определение острой токсичности исследуемых соединений проводили по методу Кербера. Установлено, что ЛД50 данных соединений при внутрибрюшинном введении крысам находятся в пределах 29,5-295 мг/кг. Это позволяет отнести исследованные соединения к III и IV классу токсичности (умеренно или малотоксичные по степени токсичности). Исследование кардиопротективной активности соединений проводили на модели острого инфаркта миокарда у крыс, который моделировали поэтапным введением изадрина и питуитрина. Было установлено, что внутрибрюшинное введение 8 из 12 соединений в дозе 1/100 ЛД50 крысам с инфарктом миокарда приводит к уменьшению гиперферментемии кардиоспецифических изоферментов креатинфосфокиназы (МВ-КФК) и лактатдегидрогеназы (ЛДГ-1), играющих роль биохимических маркеров повреждения миокарда, и снижению электрофизиологического маркера – ΣΔST при электрокардиографии. Были выявлены структурные фрагменты молекулы, сыгравшие определяющую роль в проявлении кардиопротективного действия у соединений данного ряда – β-фенилэтил, карбоксипропил, октил в положении 1, и амино- и п-метоксибензилиденамино-группы в положении 4. Установлено, что соединение МТ по степени снижения активности МВ-КФК и ЛДГ-1 в сыворотке крови животных с инфарктом миокарда, а также по уменьшению амплитуды ST на ЭКГ достоверно превышает терапевтическую эффективность метопролола., Незважаючи на досягнуті успіхи в області створення високоефективних засобів лікування серцево-судинних захворювань, проблема залишається актуальною – смертність від цієї патології залишається високою і займає 2-3 місце серед населення промислово розвинених країн. У НВО «Фарматрон» був розроблений новий напрямок зі створення нових ефективних антиангінальних засобів, який полягає в хімічній модифікації 1 і 4 положення молекули 1,2,4-триазолу шляхом введення структурних фрагментів найбільш активних лікарських препаратів і структур, що імітують сайти адренергічних рецепторів. Були отримані броміди 1-(алкіл) карбоксіалкіл-4-іліденаміно-1,2,4-триазол, синтезовані на кафедрі фармацевтичної хімії ЗДМУ під керівництвом проф. І.А.Мазура. Була досліджена кардіопротективна активність 12 сполук похідних бромідів 1-карбоксіалкіл-4-іліденаміно-1,2,4-триазол і бромідів 1-алкіл-4-іліденаміно-1,2,4-триазол. Експериментальну частину проводили на 510 білих безпородних щурах самцях масою 120-130 г, отриманих з розплідника Інституту фармакології і токсикології НАМН України. Визначення гострої токсичності досліджуваних сполук проводили за методом Кербера. Встановлено, що ЛД50 даних сполук при введенні щурам знаходяться в межах 29,5-295 мг/кг. Це дозволяє віднести досліджені сполуки до III і IV класу токсичності (помірно або малотоксичні за ступенем токсичності). Дослідження кардіопротективної активності сполук проводили на моделі гострого інфаркту міокарда у щурів, який моделювали поетапним введенням ізадрину і пітуїтрину. Було встановлено, що введення 8 з 12 сполук у дозі 1/100 ЛД 50 щурам з інфарктом міокарда призводить до зменшення гіперферментемії кардіоспецифічних ізоферментів креатинфосфокінази (МВ-КФК) і лактатдегідрогенази (ЛДГ-1), які відіграють роль біохімічних маркерів пошкодження міокарда, і до зниження електрофізіологічного маркера – ΣΔST при електрокардіографії. Були виявлені структурні фрагменти молекули, які відіграють визначальну роль у прояві кардіопротективної дії у сполук даного ряду – β-фенілетил, карбоксипропіл, октил у положенні 1 і наявність аміно- і п-метоксибензиліденаміно-групи в положенні 4. Встановлено, що сполука МТ за ступенем зниження активності МВ-КФК та ЛДГ-1 в сироватці крові тварин з інфарктом міокарда, а також зменшення амплітуди ST на ЕКГ достовірно перевищує терапевтичну ефективність метопрололу.

Cilj Procijeniti kardioprotektivni učinak sevoflurana na rad lijeve srčane klijetke za vrijeme presađivanja prjemosnice koronarne arterije na kucajućemu srcu s normalnom prijeoperacijskom funkcijom lijeve klijetke. Postupci Randomizirana kontrolirana studija uključila je 32 bolesnika kojima je anestezija inducirana sevofluranom a potom su randomizirani za primanje 1 minimalne alveolarne koncentracije (MAC) sevoflurana pri završetku udisaja (n=16) ili 2 do 3 mg kg-1 h-1 propofola (n=16). Mjereni su ubrzanje tijeka krvi u aorti, srčani indeks i frekvencija, srednji arterijski i središnji venski tlak, i to 5 minuta nakon indukcije anestezije, na početku i nakon 15 minuta trajanja ishemije, te 15 minuta nakon zatvaranja prsne kosti. Rezultati Srčana frekvencija, srednji arterijski i središnji venski tlak nisu se razlikovali ni unutar ni između dvaju skupina bolesnika. U skupini koja je primila sevofluran povećalo se ubrzanje 15 minuta nakon ishemije (10,3±3,5 m/s2; P=0,004) i 15 minuta nakon zatvaranja prsne kosti (10,7±3,9m/s2; P, Aim To evaluate the cardioprotective effect of sevoflurane on a beating heart in patients undergoing coronary artery bypass grafting with normal preoperative left ventricular function. Methods The randomized controlled study included 32 patients induced with sevoflurane and then randomized to receive either 1 minimal alveolar concentration (MAC) end-tidal concentration of sevoflurane (n = 16) or propofol (n = 16) 2 to 3 mg kg–1 hour–1. The acceleration of the aortic blood flow, cardiac index, heart rate, mean arterial pressure, and central venous pressure were measured 5 minutes after anesthesia induction, at the beginning of ischemia, 15 minutes after ischemia, and 15 minutes after sternum closure. Results There were no differences in heart rate, mean arterial pressure, and central venous pressure within each group and between groups during surgery. Acceleration increased in the sevoflurane group 15 minutes after ischemia (10.3 ± 3.5 m/s2; P = 0.004) and 15 minutes after sternum closure (10.7 ± 3.9 m/s2; P