Efectos cardiovasculares de los inhibidores del cotransportador 2 de sodio-glucosa (ISGLT2): los mecanismos del beneficio en pacientes con insuficiencia cardíaca / Cardiovascular effects of sodium-glucose co-transporter 2 inhibitors (ISGLT2)

La insuficiencia cardíaca (IC) es un problema de salud mundial. En la actualidad existe una clara asociación entre la IC y la diabetes mellitus tipo 2 (DM2), con una prevalencia cada vez mayor de pacientes que presentan concomitantemente ambas patologías. Los inhibidores del cotransportador 2 de sodio-glucosa (ISGLT2) han demostrado disminuir los eventos cardiovasculares, incluida la muerte de origen cardiovascular, por lo que se han instalado como uno de los pilares en su tratamiento. En el presente artículo se describen los principales mecanismos de acción de los ISGLT2 y sus efectos: mejora de condiciones de carga ventricular, metabolismo cardíaco, bioenergética, remodelado ventricular y sus efectos cardioprotectores directos y posiblemente antiarrítmicos.

Heart failure (HF) is a global health problem. Currently there is a clear association between HF and type 2 diabetes mellitus (DM2), with an increasing prevalence of patients presenting with both pathologies concomitantly. Sodium-glucose cotransporter 2 inhibitors (ISGLT2) have shown to significantly reduce cardiovascular events, including cardiovascular death. These results have placed ISGLT2 as one of the main pillars in the treatment of HF. This article will focus on the mechanisms of action, and their effects: improved ventricular loading conditions, cardiac metabolism, bioenergetics, ventricular remodeling, direct cardioprotective and possibly antiarrhythmic effects.

Ginsenoside Rg1 Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro / 中国结合医学杂志

OBJECTIVE@#To explore the synergic mechanism of ginsenoside Rg1 (Rg1) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs.@*METHODS@#The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg1 for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na+], potassium ions [K+] and calcium ions [Ca2+] levels, and Nav1.5, Kv4.2, and RyR2 genes expressions in each group were examined.@*RESULTS@#For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg1 had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ via regulating Nav1.5, RyR2 expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular Na+ (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular K+ (P<0.01) via regulating Nav1.5, Kv4.2, RyR2 expressions in impaired NRCMs.@*CONCLUSION@#Rg1 inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na+], [K+], and [Ca2+].

Antioxidant potential, anti-inflammatory activity, antidiabetic and cardioprotective effect of Microsechium helleri (Peyr. ) Cong / Potencial antioxidante, actividad anti-inflamatoria, efecto antidiabético y cardioprotector de Microsechium helleri (Peyr. ) Cong

Microsechium helleri (Cucurbitaceae) has been used in ethnopharmacological as a lotion to prevent hair loss, diuretic and cathartic, in the region of central Veracruz, Mexico is used as antidiabetic. The antioxidant properties of the hexanic (EHex), chloroformic (ECHCl3) and ethanolic (EEtOH) extracts, were evaluated by 2,2diphenyl-1-pychrylhydrazyl (DPPH) test, the Ferric Reducing/Antioxidant Power (FRAP) and the total phenolic content test. The anti-inflammatory effect was evaluated in the acute ear edema induced with phorbol 12-myristate 13-acetate (TPA) in mouse and the hypoglycemic and cardioprotective effects of the EEtOH were determined in rats. The EEtOH was the most active in the antioxidant potential DPPH test and the ECHCl3 was the best in the FRAP assay and the total polyphenols content. In the anti-inflammatory assay, the ECHCl3 showed the most activity. The EEtOH had the decreased the glucose levels and reduced myocardial damage. The results support the use of this plant in folk medicine in Mexico as antioxidant, anti-inflammatory, hypoglycemic and cardioprotective.

Microsechium helleri (Cucurbitaceae) se utiliza en etnofarmacología como una loción para prevenir la caída del cabello, como diurético y catártico, en la región del centro de Veracruz, México es usado como antidiabético. Las propiedades antioxidantes de los extractos hexánico (EHex), clorofórmico (ECHCl3) y etanólico (EEtOH), se evaluaron mediante la prueba de 2,2difenil-1-psililhidrazilo (DPPH), el poder reductor férrico/poder antioxidante (FRAP) y el contenido fenólico total. El efecto anti-inflamatorio se evaluó en el edema agudo de la oreja inducido con forbol 12-miristato 13-acetato (TPA) en ratones y se determinaron los efectos hipoglucémicos y cardioprotectores del EEtOH en ratas. El EEtOH fue el más activo en la prueba DPPH de potencial antioxidante y el ECHCl3 fue el mejor en el ensayo FRAP y el contenido total de polifenoles. En el ensayo antiinflamatorio, el ECHCl3 mostró la mayor actividad. El EEtOH disminuyó los niveles de glucosa y redujo el daño miocárdico. Los efectos hipoglucémicos y cardioprotector del extracto de EEtOH se determinaron en ratas, donde el extracto disminuyó los niveles de glucosa y redujo el daño miocárdico. Los resultados apoyan el uso de esta planta en la medicina popular en México como antioxidante, anti-inflamatorio, hipoglucemiante y cardioprotector.

The myocardial protective effect of propofol on rats with experimental myocardial infarction and its mechanism / 生理学报

The aim of the present study was to investigate the protective effect of propofol on the experimental myocardial infarction in rats. The myocardial infarction model was established by ligating the anterior descending branch of left coronary artery in rats. Model rats were treated with propofol. Cardiac function was evaluated by echocardiography. Cardiac hemodynamic changes were detected by multiconductor biorecorder. Pathological changes in the infarcted myocardia were detected by HE staining. The expression levels of cardiac hypertrophy marker genes and fibrosis marker proteins were analyzed by real-time quantitative PCR and Western blot. The results showed that, compared with the sham surgery group, the model group exhibited larger infarct size (> 40%), impaired heart function, and significantly increased left ventricular end-diastolic pressure (LVEDP). Propofol reduced cardiac function impairment and decreased LVEDP in the model group. Propofol significantly reduced lung weight/body weight ratio, heart weight/body weight ratio, left ventricular weight/body weight ratio and left atrial weight/body weight ratio in the model group. Furthermore, after myocardial infarction, the administration of propofol significantly improved the diastolic strain rate, down-regulated the mRNA expression levels of myocardial hypertrophy markers, atrial natriuretic peptide and β-myosin heavy chain, and reversed the up-regulation of matrix metalloproteinase 2 (MMP2), MMP9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) induced by myocardial infarction. These results suggest propofol can reduce adverse ventricular remodeling, cardiac dysfunction, myocardial hypertrophy and fibrosis after myocardial infarction, and has protective effect against the experimental myocardial infarction induced by coronary artery ligation in rats.

The cardiovascular protective effect and mechanism of calycosin and its derivatives / 中国天然药物

Cardiovascular disease is the main cause of mortality and morbidity in the world, especially in developing countries. Drug therapy is one of the main ways to treat cardiovascular diseases. Among them, great progress has been made in the treatment of cardiovascular diseases with traditional Chinese medicine. In terms of experimental research, the mechanism of traditional Chinese medicine in the treatment of cardiovascular diseases has been thoroughly discussed in vitro and in vivo. In terms of clinical treatment, traditional Chinese medicine with flavonoids, saponins and alkaloids as the main effective components has a definite effect on the treatment of cardiovascular diseases such as arrhythmia, myocardial ischemia, angina pectoris and myocardial infarction, with high safety and good application prospects. With the further research on the effective ingredients, mechanism and adverse reactions of traditional Chinese medicine, it will be beneficial to the effectiveness of traditional Chinese medicine, reduce side effects and promote the modernization of traditional Chinese medicine. Calycosin and its derivatives, the main bioactive flavonoids in Astragalus membranaceus have multiple biological effects, such as antioxidant, pro-angiogenesis, anti-tumour, and anti-inflammatory effects. Based on the above biological effects, calycosin has been shown to have good potential for cardiovascular protection. The potent antioxidant effect of calycosin may play an important role in the cardiovascular protective potential. For injured cardiac myocytes, calycosin and its derivatives can alleviate the cell damage mainly marked by the release of myocardial enzymes and reduce the death level of cardiac myocytes mainly characterized by apoptosis through various mechanisms. For vascular endothelial cells, calycosin also has multiple effects and multiple mechanisms, such as promoting vascular endothelial cell proliferation, exerting vasodilating effect and directly affecting the synthesis function of endothelial cells. The present review will address the bioactivity of calycosin in cardiovascular diseases such as protective effects on cardiac myocytes and vascular endothelial cells and elucidate main mechanism of calycosin and its derivatives to exert the above biological effects.

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway

Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.

GDF11 ameliorated myocardial ischemia reperfusion injury by antioxidant stress and up-regulating autophagy in STZ-induced type 1 diabetic rats

Abstract Purpose: To investigate whether GDF11 ameliorates myocardial ischemia reperfusion (MIR) injury in diabetic rats and explore the underlying mechanisms. Methods: Diabetic and non-diabetic rats subjected to MIR (30 min of coronary artery occlusion followed by 120 min of reperfusion) with/without GDF11 pretreatment. Cardiac function, myocardial infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) 15-F2tisoprostane, autophagosome, LC3II/I ratio and Belcin-1 level were determined to reflect myocardial injury, oxidative stress and autophagy, respectively. In in vitro study, H9c2 cells cultured in high glucose (HG, 30mM) suffered hypoxia reoxygenation (HR) with/without GDF11, hydrogen peroxide (H2O2) and autophagy inhibitor 3-methyladenine (3-MA) treatment, cell injury; oxidative stress and autophagy were assessed. Results: Pretreatment with GDF11 significantly improved cardiac morphology and function in diabetes, concomitant with decreased arrhythmia severity, infarct size, CK-MB, LDH and 15-F2tisoprostane release, increased SOD activity and autophagy level. In addition, GDF11 notably reduced HR injury in H9c2 cells with HG exposure, accompanied by oxidative stress reduction and autophagy up-regulation. However, those effects were completely reversed by H2O2 and 3-MA. Conclusion: GDF11 can provide protection against MIR injury in diabetic rats, and is implicated in antioxidant stress and autophagy up-regulation.

Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion

Abstract Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.

Anthracycline-associated cardiotoxicity in adults: systematic review on the cardioprotective role of beta-blockers

SUMMARY OBJECTIVES This study aimed at assessing the role of beta-blockers on preventing anthracycline-induced cardiotoxicity in adults. METHODS A systematic review was performed on electronic databases, including relevant studies that analysed beta-blockers as cardioprotective agents before the use of anthracyclines by adult oncologic patients. RESULTS After application of eligibility and selection criteria, eight articles were considered as high quality, complying with the proposed theme; all eight clinical trials, four of them placebo-controlled, with a total number of 655 patients included. From this sample, 281 (42.9%) used beta-blocker as intervention, and carvedilol was the most frequent (167 patients - 25.5%). Six studies were considered positive regarding the cardioprotection role played by beta-blockers, although only four demonstrated significant difference on left ventricle ejection fraction after chemotherapy on groups that used beta-blockers compared to control groups. Carvedilol and nebivolol, but not metoprolol, had positive results regarding cardioprotection. Other beta-blockers were not analysed in the selected studies. CONCLUSIONS Despite the potential cardioprotective effect of beta-blockers, as demonstrated in small and unicentric clinical trials, its routine use on prevention of anthracycline-associated cardiotoxicity demands greater scientific evidence.

RESUMO OBJETIVO Este estudo teve como objetivo analisar o papel dos betabloqueadores na prevenção da cardiotoxicidade induzida pelas antraciclinas em adultos. MÉTODOS Foi realizada uma revisão sistemática em bases de dados eletrônicos, incluindo os estudos relevantes que analisaram fármacos betabloqueadores como agentes cardioprotetores antes do início do uso de antraciclinas por pacientes oncológicos adultos. RESULTADOS Após aplicação dos critérios de elegibilidade e seleção, foram obtidos oito artigos considerados de boa qualidade, que se adequavam à temática proposta, sendo todos ensaios clínicos, quatro placebo-controlados, totalizando 655 pacientes incluídos. Destes, 281 (42,9%) fizeram uso de algum betabloqueador como intervenção, sendo o carvedilol o mais utilizado (167 pacientes - 25,5%). Seis estudos foram considerados positivos quanto à cardioproteção exercida pelos betabloqueadores, porém apenas quatro demonstraram diferença na fração de ejeção do ventrículo esquerdo após a quimioterapia nos grupos que usaram betabloqueadores em relação aos grupos controle. O carvedilol e o nebivolol, mas não o metoprolol, tiveram resultados positivos quanto à cardioproteção. Outros betabloqueadores não foram avaliados nos estudos incluídos. CONCLUSÕES Apesar de haver um potencial efeito cardioprotetor dos betabloqueadores, conforme demonstrado em ensaios clínicos pequenos e unicêntricos, sua utilização rotineira na prevenção da cardiotoxicidade associada às antraciclinas requer maiores comprovações científicas.

Cardioprotective effect of lipstatin derivative orlistat on normotensive rats submitted to cardiac ischemia and reperfusion

Abstract Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). Results: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. Conclusion: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.

Acetaminophen mitigates myocardial injury induced by lower extremity ischemia-reperfusion in rat model

Abstract Objective: The injury-reducing effect of acetaminophen, an effective analgesic and antipyretic on ischemia-reperfusion continues to attract great attention. This study analyzed the protective effect of acetaminophen on myocardial injury induced by ischemia-reperfusion in an experimental animal model from lower extremity ischemia-reperfusion. Methods: Twenty-four Sprague-Dawley female rats were randomized into three groups (n=8) as (i) control group (only laparotomy), (ii) aortic ischemia-reperfusion group (60 min of ischemia and 120 min of reperfusion) and (iii) ischemia-reperfusion + acetaminophen group (15 mg/kg/h intravenous acetaminophen infusion starting 15 minutes before the end of the ischemic period and lasting till the end of the reperfusion period). Sternotomy was performed in all groups at the end of the reperfusion period and the heart was removed for histopathological examination. The removed hearts were histopathologically investigated for myocytolysis, polymorphonuclear leukocyte (PMNL) infiltration, myofibrillar edema and focal hemorrhage. Results: The results of histopathological examination showed that acetaminophen was detected to particularly diminish focal hemorrhage and myofibrillar edema in the ischemia-reperfusion + acetaminophen group (P<0.001, P=0.011), while there were no effects on myocytolysis and PMNL infiltration between the groups (P=1.000, P=0.124). Conclusion: Acetaminophen is considered to have cardioprotective effect in rats, by reducing myocardial injury induced by abdominal aortic ischemia-reperfusion.

Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury

Abstract Purpose: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). Methods: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. Results: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. Conclusions: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/ oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Espectro dos efeitos cardiovasculares da dobutamina - de voluntários saudáveis a pacientes em choque séptico / The spectrum of cardiovascular effects of dobutamine - from healthy subjects to septic shock patients

RESUMO A dobutamina é o inotrópico mais comumente utilizado em pacientes com choque séptico, com o objetivo de aumentar o débito cardíaco e corrigir a hipoperfusão. Embora alguns ensaios clínicos tenham demonstrado que a dobutamina pode melhorar a hemodinâmica sistêmica e regional, outras pesquisas identificaram que seus efeitos são heterogêneos e imprevisíveis. Nesta revisão, analisamos as propriedades farmacodinâmicas da dobutamina e seus efeitos fisiológicos. Nosso objetivo foi demonstrar que os efeitos da dobutamina podem diferir entre voluntários saudáveis, estudos experimentais e insuficiência cardíaca clínica, em modelos de estudo em animais e em pacientes com choque séptico. Discutimos as evidências que suportam a afirmativa de que a dobutamina utilizada no tratamento do choque séptico frequentemente se comporta como fármaco cronotrópico e vasodilatador, sem evidências de ação inotrópica. Como seus efeitos colaterais são muito comuns e os benefícios terapêuticos não são claros, sugerimos que ela deve ser utilizada com cautela no choque séptico. Antes de uma decisão terapêutica definitiva, a eficácia e a tolerabilidade da dobutamina devem ser avaliadas por um tempo curto com monitoramento estrito de seus efeitos positivos e efeitos colaterais negativos.

ABSTRACT Dobutamine is the inotrope most commonly used in septic shock patients to increase cardiac output and correct hypoperfusion. Although some experimental and clinical studies have shown that dobutamine can improve systemic and regional hemodynamics, other research has found that its effects are heterogenous and unpredictable. In this review, we analyze the pharmacodynamic properties of dobutamine and its physiologic effects. Our goal is to show that the effects of dobutamine might differ between healthy subjects, in experimental and clinical cardiac failure, in animal models and in patients with septic shock. We discuss evidence supporting the claim that dobutamine, in septic shock, frequently behaves as a chronotropic and vasodilatory drug, without evidence of inotropic action. Since the side effects are very common, and the therapeutic benefits are unclear, we suggest that dobutamine should be used cautiously in septic shock. Before a definitive therapeutic decision, the efficacy and tolerance of dobutamine should be assessed during a brief time with close monitoring of its positive and negative side effects.

The protective cardiac effects of Β-myrcene after global cerebral ischemia/reperfusion in C57BL/J6 mouse

ABSTRACT PURPOSE: To investigate the protective effect of β-myrcene (MYR) on oxidative and histological damage in mice heart tissue caused global cerebral ischemia/reperfusion (IR) in C57BL/J6 mice. METHODS: Animals(n=40) were randomly divided into four groups: (1)control, (2)IR, (3)MYR and (4)MYR+IR. The control group was received 0.1% carboxymethyl cellulose as a vehicle following a medial incision without carotid occlusion. In the IR group, the bilateral carotid arteries were clipped for 15min, and treated with the vehicle intraperitoneally(ip) for 10 days. MYR (200mg/kg) was received dissolved in 0.1%CMC for 10 days. In the MYR+IR group, the IR model was applied exactly as in the IR group, and then they were treated with MYR 10 days. RESULTS: The cerebral IR caused oxidative damage (increase TBARS, decrease antioxidant parameters). Treatment of MYR was increased in GSH,GPx,CAT,SOD activity while TBARS level was decreased. In addition, degenerative changes in I/R group heart tissue were ameliorated by MYR administration. CONCLUSİON: The administration of β-myrcene protects oxidative and histological damage in the heart tissue after global ischemia-reperfusion and may be useful safe alternative treatment for cardiac tissue after ischemic stroke.

Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure / A Pentoxifilina Atenua a Remodelação Cardíaca Induzida pela Exposição á Fumaça de Cigarros

Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

Resumo Fundamento: Exposição à fumaça de cigarros é um fator significativo de risco para a remodelação cardíaca. Nesta condição, estão presentes inflamação, estresse oxidativo, anormalidades do metabolismo energético, apoptose e hipertrofia. A pentoxifilina tem propriedades anti-inflamatórias, anti-apoptóticas, anti-trombóticas e anti-proliferativas. Objetivo: O presente estudo testou a hipótese de que a pentoxifilina atenuaria a remodelação cardíaca induzida pelo fumo. Métodos: Ratos Wistar foram distribuídos em quatro grupos: Controle (C), Pentoxifilina (PX), Fumaça de Cigarro (FC), e PX-FC. Depois de dois meses, foram feitos ecocardiografia, medição de pressão arterial invasiva e estudos bioquímicos e histológicos. Os grupos foram comparados por ANOVA de duas vias com nível de significância de 5%. Resultados: FC aumentou o diâmetro e a área do átrio esquerdo, o que foi atenuado pela PX. No estudo de coração isolado, FC diminuiu a derivada positiva (+dp/dt), o que foi atenuado por PX. Os antioxidantes enzima superóxido-dismutase e glutationa peroxidase foram reduzidos no grupo FC; PX recuperou essas atividades. FC aumentou o lactato desidrogenase (LDH) e reduziu as desidrogenases 3-hidroxiacil Coenzima A (OH-DHA) e citrato sintase (CS). PX atenuou alterações de LDH, 3-OH-DHA e CS no grupo PX-FC. FC aumentou IL-10, ICAM-1 e caspase-3. PX não teve influência nestas variáveis. Conclusão: FC induziu remodelação cardíaca, associada a um aumento de inflamação, estresse oxidativo, apoptose e metabolismo energético alterado. PX atenuou remodelação cardíaca, reduzindo estresse oxidativo e melhorando bioenergética cardíaca, mas não agiu nas citocinas cardíacas nem na apoptose.

Cardio Protective Effect of Dark Chocolate Components: Mechanisms of Actions.

Chocolate is made from the seeds of a tropical rainforest tree called “Theobroma cacao”. When compared with other food sources based on oxygen radical absorbance capacity (ORAC) measurement, dark chocolate is a major source of flavonols with highest antioxidant levels. Some of the health benefits of cocoa consumption include antioxidant properties such as polyphenolic compounds, among others are monomeric flavanols, epicatechin, catechin and oligomeric procyanidins. Both experimental and observational studies have suggested that chocolate consumption has a positive influence on human health, with antioxidant, antihypertensive, anti-inflammatory, anti-atherogenic, and antithrombotic effects as well as influence on insulin sensitivity, vascular endothelial function, and bioavailability of nitric oxide. In addition, dark chocolate consumption may alter lipid effects, by lowering total and low density lipoproteins and increasing high density lipoprotein cholesterol levels. The antioxidants found in chocolate have been shown to inhibit plasma lipid oxidation probably by scavenging free radical species. There are some experimental studies to prove that flavonoids could prevent LDL oxidation in vitro by scavenging radical species or sequestering metal ions. Dark chocolate (DC) has beneficial effects in the prevention of cardiovascular diseases (CVD) due to its antiinflammatory and antioxidant properties. Polyphenols rich dark chocolate showed progress in insulin sensitivity and decreased blood pressure in healthy subjects. Dark Chocolate has a dual effect on platelets by decreasing platelet aggregation and also it reduces platelet adhesion. Chocolate extends its great beneficial effect from being by and large a palatable pleasant and hence sustainable therapeutic option. Thus, dark chocolate may be suggested as a potential delicacy and one of the agents for the prevention and control of cardiometabolic syndrome.

Ivabradine Improves Heart Rate Variability in Patients with Nonischemic Dilated Cardiomyopathy / Ivabradina Melhora a Variabilidade da Frequência Cardíaca em Pacientes com Cardiomiopatia Dilatada Não Isquêmica

Background: Ivabradine is a novel specific heart rate (HR)-lowering agent that improves event-free survival in patients with heart failure (HF). Objectives: We aimed to evaluate the effect of ivabradine on time domain indices of heart rate variability (HRV) in patients with HF. Methods: Forty-eight patients with compensated HF of nonischemic origin were included. Ivabradine treatment was initiated according to the latest HF guidelines. For HRV analysis, 24-h Holter recording was obtained from each patient before and after 8 weeks of treatment with ivabradine. Results: The mean RR interval, standard deviation of all normal to normal RR intervals (SDNN), the standard deviation of 5-min mean RR intervals (SDANN), the mean of the standard deviation of all normal-to-normal RR intervals for all 5-min segments (SDNN index), the percentage of successive normal RR intervals exceeding 50 ms (pNN50), and the square root of the mean of the squares of the differences between successive normal to normal RR intervals (RMSSD) were low at baseline before treatment with ivabradine. After 8 weeks of treatment with ivabradine, the mean HR (83.6 ± 8.0 and 64.6 ± 5.8, p < 0.0001), mean RR interval (713 ± 74 and 943 ± 101 ms, p < 0.0001), SDNN (56.2 ± 15.7 and 87.9 ± 19.4 ms, p < 0.0001), SDANN (49.5 ± 14.7 and 76.4 ± 19.5 ms, p < 0.0001), SDNN index (24.7 ± 8.8 and 38.3 ± 13.1 ms, p < 0.0001), pNN50 (2.4 ± 1.6 and 3.2 ± 2.2 %, p < 0.0001), and RMSSD (13.5 ± 4.6 and 17.8 ± 5.4 ms, p < 0.0001) substantially improved, which sustained during both when awake and while asleep. Conclusion: Our findings suggest that treatment with ivabradine improves HRV in nonischemic patients with HF. .

Fundamento: A ivabradina é um novo agente redutor específico da frequência cardíaca (FC) que melhora a sobrevida livre de eventos de pacientes com insuficiência cardíaca (IC). Objetivo: Avaliar o efeito da ivabradina nos índices temporais da variabilidade da frequência cardíaca (VFC) em pacientes com IC. Métodos: Quarenta e oito pacientes com IC compensada de etiologia não-isquêmica foram incluídos no estudo. O tratamento com ivabradina foi iniciado de acordo com as recomendações mais recentes para a IC. O Holter de 24 horas foi utilizado para analisar os índices da VFC em cada paciente antes e após 8 semanas de tratamento com ivabradina. Resultados: Todos os índices da VFC, o intervalo RR médio, o desvio padrão de todos os intervalos RR normais (DPNN), o desvio padrão de intervalos RR médios de 5 minutos (DPNNM), a média do desvio padrão de todos os intervalos RR normais para todos os segmentos de 5 minutos (índice DPNN), porcentagem de intervalos RR normais sucessivos superiores a 50 milissegundos (pNN50), e a raiz quadrada da média dos quadrados das diferenças entre intervalos RR sucessivos (RMQQD) apresentaram redução no ínicio do estudo, antes do tratamento com ivabradina. Após 8 semanas de tratamento com ivabradina, as médias das FC (83,6 ± 8,0 e 64,6 ± 5,8, p < 0,0001) e todos os índices da VFC, médias dos intervalos RR (713 ± 74 e 943 ± 101 ms, p < 0,0001), DPNN (56,2 ± 15,7 e 87,9 ± 19,4 ms, p < 0,0001), DPNNM (49,5 ± 14,7 e 76,4 ± 19,5 ms, p < 0,0001), índice DPNN (24,7 ± 8,8 e 38,3 ± 13,1 ms, p < 0,0001), pNN50 (2,4 ± 1,6 e 3,2 ± 2,2%, p < 0,0001) e RMQQD (13,5 ± 4,6 e 17,8 ± 5,4 ms , p < 0,0001), foram substancialmente melhorados, e permaneceram nestas ...

Antioxidant and cardio protective effect of palm oil leaves extract [standardized ethanolic fraction] in rats' model of saturated fats induced metabolic disorders

Recently, it is suggested to use POLE [palm oil leaf extract] as a nutraceutical health product in food industry due to its newly discovered content of polyphenols and antioxidant vitamins. In the experiment, the antioxidant and anti-lipid-peroxidation activities of the extract were confirmed using; DPPH [1-diphenyl-2-picryl-hydrazil] radical scavenging activity, ferric ion induced lipid peroxidation inhibition, reducing power and hydrogen peroxide scavenging activity assays. The cardio-protective activity was studied in vivo using a model of metabolic syndrome induced by high fat diet. Lipid profile, obesity indices, renal tubular handling of water and electrolytes, blood pressure and arterial stiffness were measured at the end of the treatment period. Sprague Dawley rats weighing 150-200 g were divided into six groups, viz; group C; was treated as a negative control and fed with standard rodents chow, group H; was treated as a positive control and fed with an experimental diet enriched with saturated free fatty acids for 8 weeks, groups HP0.5, HP1 and HP2 which were fed with 0.5,1 and 2 g/kg [body weight] /day of POLE orally during the last 24 days of the high fat diet feeding period and group P; fed with highest dose of POLE. Results revealed that POLE possesses a cardio-protective effect which is ascribed to its content of polyphenols.

Cardioprotective effect of root extract of Picrorhiza kurroa (Royle Ex Benth) against isoproterenol-induced cardiotoxicity in rats.

Normal rats pre-treated with P. kurroa (200 mg/kg) alone did not showed significant change, however, isoproterenol (ISP) administration resulted in hemodynamic and left ventricular dysfunction, oxidative stress, and lipid peroxidation. Such cardiac dysfunction was significantly prevented by P. kurroa root extract pre-treatment. Pre-treatment significantly attenuated the ISP-induced oxidative stress by restoring myocardial superoxide dismutase, catalase, and glutathione peroxidase enzymes except reduced glutathione content. P. kurroa pre-treatment markedly attenuated the ISP-induced rise in lipid peroxidation, thereby prevented leakage of myocyte creatine kinase-MB and lactate dehydrogenase enzymes. The results suggest that P. kurroa root extract possesses significant cardioprotective effect, which may be attributed to its antioxidant, anti-peroxidative, and myocardial preservative properties.