Left ventricular diastolic dysfunction

左心室舒张功能障碍
  • 文章类型: Editorial
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  • 文章类型: Journal Article
    抗信号识别颗粒(SRP)抗体,免疫介导坏死性肌病的标志物,据报道与心脏受累有关;然而,它们是否对心肌有致病性尚不清楚。我们的目标是,因此,通过体内和体外研究探讨抗SRP抗体对心肌的致病性。
    总免疫球蛋白G(IgG),从抗SRP抗体阳性的患者中纯化,被动转移到C57BL/6小鼠中。通过超声心动图和心室压力-容积环评估心功能;使用苏木精-伊红染色分析心脏组织学变化,黄连红染色,免疫荧光和免疫组织化学。此外,活性氧(ROS)的形成是通过二氢乙啶(DHE)染色评估;线粒体形态和功能使用透射电镜和海马线粒体呼吸测定评估,分别。随后对我们中心的肌炎队列进行了心脏评估。
    抗SRP抗体阳性患者的总IgG被动转移后,C57BL/6小鼠出现显著的左心室舒张功能障碍(LVDD)。转录组学分析和相应的实验显示,实验小鼠心脏的氧化应激和线粒体损伤增加。暴露于抗SRP特异性IgG的心肌细胞,然而,用N-乙酰半胱氨酸治疗后恢复正常的线粒体代谢,ROS清除剂.此外,抗SRP抗体阳性的患者在倾向评分匹配后,与相应患者相比,其舒张功能较差,但收缩功能相当.
    抗SRP抗体可能通过促进ROS产生和随后的心肌线粒体损伤在LVDD的发展中起致病作用。抑制氧化应激可有效逆转抗SRP抗体诱导的LVDD。
    UNASSIGNED: Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through in vivo and in vitro studies.
    UNASSIGNED: Total immunoglobulin G (IgG), purified from patients with positive anti-SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure-volume loop; cardiac histological changes were analysed using haematoxylin-eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments.
    UNASSIGNED: After the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching.
    UNASSIGNED: Anti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.
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    文章类型: Journal Article
    Type 2 diabetes mellitus is one of the most common non-infectious diseases in the world. Among people with type 2 diabetes, patients of the older age group. An in understanding of the early cardiovascular manifestations of diabetes occupies an important place in international research and prevention programs, given that cardiac vascular complications are the cause of death in patients with diabetes. Recent studies evaluating left ventricular diastolic dysfunction as a characteristic predictor of diabetic cardiomyopathy by echocardiography. In accordance with the recommendations for diastolic dysfunction, have shown that the algorithm of the informative algorithm is used to determine left ventricular diastolic dysfunction in patients with prognosis in predicting cardiovascular complications.
    Сахарный диабет 2-го типа (СД2) является одним из самых распространенных неинфекционных заболеваний в мире. Среди лиц с СД2 преобладают пациенты старшей возрастной группы. Углубленное понимание ранних сердечно-сосудистых проявлений диабета занимает важное место в международных исследованиях и программах профилактики, учитывая, что сердечно-сосудистые осложнения являются основной причиной смерти пациентов с диабетом. Последние исследования оценки диастолической дисфункции ЛЖ методом эхо-КГ как характерного предиктора развития кардиомиопатии показали, что обновленный алгоритм более информативен для определения диастолической дисфункции ЛЖ у пациентов при прогнозировании сердечно-сосудистых осложнений.
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  • 文章类型: Journal Article
    目的:舒张功能障碍是介于高血压和心力衰竭之间的重要病理生理中介。在过去的二十年里,射血分数(EF)正常或接近正常的心力衰竭患者的患病率增加到60%左右.因此,它对人口造成很大的发病率和死亡率风险。鉴于目前的高流行情况,缺乏循证治疗,和有限的临床试验,本研究旨在评估Unani制剂如何影响左心室舒张功能的改善.
    方法:这项临床试验是随机的,安慰剂对照研究,涉及35名参与者,试验组18人,对照组17人。试验组接受3.5g胶囊形式的多草药Unani制剂以及35mLBoragoofficinalisL.(Arq-e-Gaozaban)的提取物,饭后分为两剂。同时,对照组在8周内接受相同方式的安慰剂.每15天进行一次随访,以评估所有参与者的主观和客观参数。
    结果:从基线到试验结束,测试制剂显示出呼吸困难和舒张功能的显着改善(p<0.05),与对照相比,心悸的轻微改善(p>0.05)和易疲劳性的高度显著改善(p=0.001)。
    结论:本研究显示了试验药物在增强左心室舒张功能和减轻与心室舒张功能障碍相关的其他症状方面的有效性。然而,在Unani医学中,需要进行更长时间随访的更多研究,以阐明其疗效,并建立针对心室舒张功能不全的最佳治疗方法.
    OBJECTIVE: Diastolic dysfunction represents an important pathophysiological intermediate between hypertension and heart failure. In the last two decades, the prevalence of heart failure patients having normal or near normal ejection fraction (EF) has increased to around 60 %. It thus poses a great morbidity and mortality risk to the population. In view of present scenario of high prevalence, lack of evidence-based therapy, and limited clinical trials, this study aimed to evaluate how a Unani formulation affects the improvement of the left ventricular diastolic function.
    METHODS: This clinical trial was set up as a randomized, placebo-controlled study involving 35 participants, with 18 individuals in the test group and 17 in the control group. Test group received 3.5 g of a polyherbal Unani formulation in capsule form along with 35 mL of an extract of Borago officinalis L. (Arq-e-Gaozaban), divided into two doses after meals. Meanwhile, the control group received a placebo in the same manner over an eight-week period. Follow-ups were conducted every 15 days to assess both subjective and objective parameters in all participants.
    RESULTS: The test formulation shows significant improvement in dyspnea and diastolic function from baseline to the end of trial (p<0.05), slight improvement in palpitations (p>0.05) and highly significant improvement in easy fatigability (p=0.001) as compared to the control.
    CONCLUSIONS: The present study shows the effectiveness of the test drug in enhancing the diastolic function of left ventricle and alleviating other symptoms associated with ventricular diastolic dysfunction. Nevertheless, additional research with longer follow-up durations is necessary to clarify its efficacy and establish optimal treatment approaches for ventricular diastolic dysfunction in Unani medicine.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    背景:左心室舒张功能障碍(LVDD)是心力衰竭的表现,其发病率和患病率每年都在增加。目前,LVDD没有药物治疗,强调迫切需要新的治疗发现。人参皂苷常用于心血管治疗。以前的研究已经合成了人参皂苷前体分子,20S-O-Glc-DM(C20DM),通过生物合成。C20DM显示出更高的生物利用度,生态友好,与传统人参皂苷相比,成本效益高,将其定位为治疗LVDD的有希望的选择。
    目的:本研究首先记录了C20DM对LVDD的治疗活性,并揭示了其潜在的作用机制。为C20DM作为一种新的心血管治疗药物提供了药理学基础。
    方法:在本研究中,建立小鼠LVDD模型和ISO诱导的H9C2细胞损伤模型。细胞活力,ROS和Ca2+水平,线粒体膜电位,在体外实验中评估了与线粒体生物发生和自噬相关的蛋白质。动物实验包括给药3周,以验证C20DM的治疗效果及其对线粒体和自噬的影响。
    结果:研究表明C20DM在治疗LVDD方面比美托洛尔更有效,显着降低E/A比率,e\'/a\'比率,和IVRT,改善心肌炎症和纤维化。C20DM影响PGC-1α的活性,下调PINK1和Parkin,从而加强线粒体质量控制,恢复线粒体氧化呼吸和膜电位。此外,C20DM通过AMPK-mTOR-ULK1通路减少心肌细胞过度自噬,减少心肌细胞肥大和损伤。
    结论:总体而言,我们的研究表明,C20DM有可能通过调节线粒体质量控制和细胞自噬来增强LVDD,使其成为心力衰竭治疗的一个有希望的选择。
    BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is a manifestation of heart failure, with both its incidence and prevalence increasing annually. Currently, no pharmacological treatments are available for LVDD, highlighting the urgent need for new therapeutic discoveries. Ginsenosides are commonly used in cardiovascular therapy. Previous research has synthesized the ginsenoside precursor molecule, 20S-O-Glc-DM (C20DM), through biosynthesis. C20DM shows greater bioavailability, eco-friendliness, and cost-effectiveness compared to traditional ginsenosides, positioning it as a promising option for treating LVDD.
    OBJECTIVE: This study firstly documents the therapeutic activity of C20DM against LVDD and unveils its potential mechanisms of action. It provides a pharmacological basis for C20DM as a new cardiovascular therapeutic agent.
    METHODS: In this study, models of LVDD in mice and ISO-induced H9C2 cell damage were developed. Cell viability, ROS and Ca2+ levels, mitochondrial membrane potential, and proteins associated with mitochondrial biogenesis and autophagy were evaluated in the in vitro experiments. Animal experiments involved administering medication for 3 weeks to validate the therapeutic effects of C20DM and its impact on mitochondria and autophagy.
    RESULTS: Research has shown that C20DM is more effective than Metoprolol in treating LVDD, significantly lowering the E/A ratio, e\'/a\' ratio, and IVRT, and ameliorating myocardial inflammation and fibrosis. C20DM influences the activity of PGC-1α, downregulates PINK1 and Parkin, thereby enhancing mitochondrial quality control, and restoring mitochondrial oxidative respiration and membrane potential. Furthermore, C20DM reduces excessive autophagy in cardiomyocytes via the AMPK-mTOR-ULK1 pathway, diminishing cardiomyocyte hypertrophy and damage.
    CONCLUSIONS: Overall, our research indicates that C20DM has the potential to enhance LVDD through the regulation of mitochondrial quality control and cellular autophagy, making it a promising option for heart failure therapy.
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  • 文章类型: Journal Article
    库欣综合征(CS)与心力衰竭的风险增加有关,通常最初表现为左心室舒张功能障碍(LVDD)。在这项研究中,我们旨在通过纳入身体成分参数来探索CS中LVDD的潜在危险因素。
    对诊断为不小于18岁的内源性CS的患者进行了回顾性研究。对照组由与CS患者性别相匹配的健康个体组成,年龄,BMI。应用LIFEx软件(7.3版)在非对比胸部CT上测量心外膜脂肪组织体积(EATV),以及第一腰椎水平的腹部脂肪组织和骨骼肌质量。超声心动图用于评估左心室(LV)舒张功能。检查了与早期LVDD有关的身体成分和临床数据。
    共纳入86例CS患者和86例健康对照。与对照组相比,CS患者的EATV明显更高(150.33cm3[125.67,189.41]vs90.55cm3[66.80,119.84],p<0.001)。与健康的患者相比,CS患者的内脏脂肪明显增加,但骨骼肌减少。根据E/A比评估的LV舒张功能,CS患者的LVDD患病率更高(p<0.001)。EATV是CS患者LVDD的独立危险因素(OR=1.015,95CI1.003~1.026,p=0.011)。如果CS患者的EATV切点设置为139.252cm3,LVDD诊断的敏感性和特异性分别为84.00%和55.60%,分别。
    CS与EAT和内脏脂肪的显著积累有关,减少骨骼肌质量,LVDD患病率增加。EATV是LVDD的独立危险因素,提示EAT在CSLVDD发展中的潜在作用。
    本研究通过纳入身体成分参数,探索内源性CS中LVDD的潜在危险因素。EATV被确定为LVDD的独立危险因素。减少皮质醇诱导的过度EAT积累的针对性治疗干预措施可能有望减轻CS患者LVDD发展的风险。
    UNASSIGNED: Cushing\'s syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters.
    UNASSIGNED: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD.
    UNASSIGNED: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively.
    UNASSIGNED: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.
    This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.
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  • 文章类型: Journal Article
    随着研究的增加,沉默酶(SIRT)蛋白家族已被越来越多的人所了解。研究表明,SIRTs可以帮助新陈代谢并影响各种生理过程,比如动脉粥样硬化,心力衰竭(HF),高血压,2型糖尿病,和其他相关疾病。虽然射血分数保留HF(HFpEF)的发病机制尚未明确,SIRTs在其发展中发挥作用。因此,SIRT可能会提供一种新的诊断方法,治疗,并将预防HFpEF作为新的治疗干预目标。
    With increasing research, the sirtuin (SIRT) protein family has become increasingly understood. Studies have demonstrated that SIRTs can aid in metabolism and affect various physiological processes, such as atherosclerosis, heart failure (HF), hypertension, type 2 diabetes, and other related disorders. Although the pathogenesis of HF with preserved ejection fraction (HFpEF) has not yet been clarified, SIRTs have a role in its development. Therefore, SIRTs may offer a fresh approach to the diagnosis, treatment, and prevention of HFpEF as a novel therapeutic intervention target.
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  • 文章类型: Journal Article
    心外膜脂肪组织(EAT)已成为全身性炎症性疾病和心血管疾病之间的媒介,因此,可能在系统性硬化症(SSc)的心脏受累的病理生理学中发挥作用。这项研究的目的是评估EAT和左心室(LV)功能之间的相关性,并确定EAT在SSc患者中的预后价值。
    连续接受非对比胸部计算机断层扫描和超声心动图检查的SSc患者。使用专用软件定量EAT质量。研究终点为全因死亡率。共有230例SSc患者(年龄53±15岁,14%的男性)被包括在内。EAT质量的中值为67g(四分位间距:45-101g)。与EAT质量较小(<67g)的患者相比,EAT质量增加(≥67g)的患者显示出更多的左心室舒张功能受损。即使在调整了年龄和合并症之后,EAT质量与LV舒张功能参数独立相关。在8年的中位随访中,42人死亡。Kaplan-Meier分析显示,与EAT质量较小的患者相比,EAT质量增加的患者全因死亡率较高(29%vs.7%;P<0.001)。在多变量分析中,调整重要协变量后,EAT与全因死亡率独立相关(HR:1.006;95%CI:1.001-1.010)。
    在SSc患者中,EAT与LV舒张功能障碍和较高的死亡率独立相关。
    UNASSIGNED: Epicardial adipose tissue (EAT) has emerged as a mediator between systemic inflammatory disorders and cardiovascular disease, and may therefore play a role in the pathophysiology of cardiac involvement in systemic sclerosis (SSc). The aim of this study was to assess the correlation between EAT and left ventricular (LV) function, and to determine the prognostic value of EAT in patients with SSc.
    UNASSIGNED: Consecutive patients with SSc who underwent non-contrast thorax computed tomography and echocardiography were included. EAT mass was quantified using dedicated software. The study endpoint was all-cause mortality. A total of 230 SSc patients (age 53 ± 15 years, 14% male) were included. The median value of EAT mass was 67 g (interquartile range: 45-101 g). Patients with increased EAT mass (≥67 g) showed more impaired LV diastolic function as compared with patients with less EAT mass (<67 g), and even after adjusting for age and comorbidities, EAT mass was independently associated with LV diastolic function parameters. During a median follow-up of 8 years, 42 deaths occurred. Kaplan-Meier analysis showed that patients with increased EAT mass had higher all-cause mortality rate as compared with patients with less EAT mass (29% vs. 7%; P < 0.001). In the multivariable analysis, EAT was independently associated with all-cause mortality after adjusting for important covariates (HR: 1.006; 95% CI: 1.001-1.010).
    UNASSIGNED: In patients with SSc, EAT is independently associated with LV diastolic dysfunction and higher mortality rate.
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  • 文章类型: Journal Article
    围产期发病的母亲重度抑郁症对母亲和发育中的胎儿构成健康风险。使用慢性轻度应激的大鼠模型,我们先前报道了母亲围产期应激对其后代的神经发育影响;本研究调查了母亲围产期应激对其后代的心血管影响.根据血压和超声心动图参数评估心血管影响。通过三因素方差分析检查的结果表明,心血管参数与母体围产期压力显着相关,和后代的性别和年龄。在暴露于压力的大坝的青春期女性和成年男性后代中观察到血压升高。超声心动图显示,青春期压力暴露的雌性后代左心房尺寸增加,左心室收缩功能降低。在成年压力暴露的雄性后代中,观察到舒张末期室间隔厚度增加和左心室舒张功能障碍。通过使用高效液相色谱法评估延髓中神经递质及其代谢物的水平,在暴露于压力的成年后代中检查了心血管影响的潜在机制。高香草酸的显著减少,多巴胺代谢产物和多巴胺能活性的指示剂,在成年暴露于压力的雌性后代中观察到。这些结果表明,围产期母亲的压力对后代的心血管系统具有显着的性别和年龄依赖性影响,并延伸到成年期,并暗示了多代人的影响。所提供的数据迫切需要随访,以确认其潜在的临床和公共卫生相关性。
    Maternal major depressive disorder with peripartum onset presents health risks to the mother and the developing fetus. Using a rat model of chronic mild stress, we previously reported on the neurodevelopmental impact of maternal perinatal stress on their offspring. This study examined the cardiovascular impact of maternal perinatal stress on their offspring. The cardiovascular impact was assessed in terms of blood pressure and echocardiographic parameters. The results examined by a three-way ANOVA showed a significant association of cardiovascular parameters with maternal perinatal stress and offspring sex and age. Increased blood pressure was observed in adolescent female and adult male offspring of stress-exposed dams. Echocardiography showed an increase in left atrial dimension and a reduction in left ventricular systolic function in adolescent stress-exposed female offspring. Increased interventricular septum thickness at end-diastole and left ventricular diastolic dysfunction were observed in adult stress-exposed male offspring. The underlying mechanisms of cardiovascular impact were examined in stress-exposed adult offspring by assessing the levels of neurotransmitters and their metabolites in the medulla oblongata using high-performance liquid chromatography. A significant decrease in homovanillic acid, a dopamine metabolite and indicator of dopaminergic activity, was observed in adult stress-exposed female offspring. These results suggest a significant sex- and age-dependent impact of maternal stress during the peripartum period on the cardiovascular system in the offspring that extends to adulthood and suggests a multigenerational effect. The presented data urgently need follow-up to confirm their potential clinical and public health relevance.NEW & NOTEWORTHY We demonstrate that maternal perinatal stress is associated with sex- and age-dependent impact on the cardiovascular system in their offspring. The effect was most significant in adolescent female and adult male offspring. Observed changes in hemodynamic parameters and dopaminergic activity of the medulla oblongata are novel results relevant to understanding the cardiovascular impact of maternal perinatal stress on the offspring. The cardiovascular changes observed in adult offspring suggest a potential long-term, multigenerational impact of maternal perinatal stress.
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