成纤维细胞向内皮细胞转分化促进缺血性心脏病血管新生

细胞转分化通过重编程或小分子化学诱导的方式使一种分化细胞类型直接转化为另一种期望的细胞类型。该文介绍成纤维细胞向内皮细胞转分化策略及促进缺血性心脏病血管新生的应用前景。     

左旋卡尼汀治疗缺血性心脏病心力衰竭临床观察

慢性充血性心力衰竭患者存在心肌代谢紊乱，越来越引起人们注意，国外研究提示心肌能量代谢失调是心衰的病理机制之一。作者应用左旋卡尼汀(L-CN)治疗缺血性心脏病(IHD)心力衰竭患者，评估其疗效和安全性。     

内皮祖细胞与缺血性心脏病

缺血性心脏病是一类严重威胁人类健康的疾患,其发生、发展和预后与血管内皮密切相关。研究发现内皮祖细胞也参与出生后的内皮修复和血管新生过程,提示其在缺血性心脏病中的重要治疗作用和临床运用前景。     

川芎嗪及参麦注射液治疗缺血性心脏病心力衰竭50例

目的观察川芎嗪注射液联合参麦注射液治疗缺血性心脏病心力衰竭的近期疗效。方法100例缺血性心脏病心力衰竭病人按数字表法随机分为两组。对照组（50例）采用常规治疗，如血管紧张素转换酶抑制剂（ACEI）、洋地黄制剂、利尿剂、血管扩张剂等；治疗组（50例）应用川芎嗪注射液200mg联合参麦注射液50mL静脉输注，均每日1次；除不用洋地黄制剂、消心痛、硝酸甘油等扩血管药物外，其余治疗同对照组。两组均以10d为1个疗程，连用2个疗程。观察用药前后心率（HR）、心排血量（CO）、左室射血分数（LVEF）和左室舒张末期压力（LVEDP）等心功能参数及心功能分级、临床症状和体征的变化，并观察两组药物不良反应等。结果治疗组临床疗效明显改善，治疗组总有效率达92．0％，对照组为72．0％（P〈0．01）；两组治疗后LVEF、LVEDP均明显改善，治疗组药物不良反应和毒性作用发生率低于对照组。结论川芎嗪注射液联合参麦注射液治疗缺血性心脏病心力衰竭近期疗效显著，且无明显不良反应。     

缺血性心脏病心力衰竭合并脑梗死25例临床分析

缺血性心脏病心力衰竭过程中发生脑梗死不但加重病情,还给治疗带来很大困难。我院自2003年1月至2005年6月间收治25例缺血性心脏病心力衰竭合并脑梗死患者,经综合治疗疗效满意,现分析如下。1临床资料1·1一般资料:2003年1月至2005年6月收治的缺血性心脏病心力衰竭患者308例,均经心电图、超声心动图或选择性冠状动脉造影检查确诊,按NYHA分级心功能Ⅲ~Ⅳ级。治疗过程中发生脑梗死25例(发生率8·1%),男15例,女10例,年龄48~79(67·8±8·5)岁,心功能均为Ⅳ级,其中合并高血压11例、心房纤颤4例、糖尿病4例,有陈旧性心肌梗死病史者3例,陈旧性心肌…     

骨髓间质干细胞在缺血性心脏病中的应用

骨髓间质干细胞(MSCs)是一种多能造血于细胞,在一定诱导条件下,可分化为多种造血外组织细胞,如骨细胞、软骨细胞、 心肌细胞等,因此,在组织工程方面具有广泛的应用前景。近年来,MSCs在缺血性心脏病中的应用价值已得到证实和肯定,从而为 缺血性心脏病的治疗带来了新的契机。本文就骨髓间质干细胞在缺血性心脏病中的应用进行了回顾和展望。     

血管内皮细胞生长因子质粒治疗慢性缺血性心脏病的实验研究

以分子生物学手段来治疗组织缺血的方式被称为“治疗性血管生成”或“分子搭桥”,使用血管内皮细胞生长因子 (VEGF)基因治疗下肢或心肌缺血的治疗效果仍存在争议 ,我们在慢性心肌缺血模型基础上对VEGF基因的疗效进行了评价 ,为临床应用提供依据。材料与方法　　雄性小型猪 ,体重 (2 7 0± 3 2 )kg。全麻后左开胸于冠状动脉左回旋支近端套入慢性缩窄环 (内径 2 75mm ,ResearchInstrumentSW公司产品)。 4周后进行冠状动脉造影、心肌灌注单电子发射计算机断层扫描 (MPSPECT)和负荷超声心动图评价 ,符合慢性缺血标准的动物进入以后实验…     

血清尿酸水平与缺血性心脏病慢性心力衰竭相关性探讨

研究表明慢性心力衰竭(心衰)患者血清尿酸水平常升高,且与冠心病、高血压等心血管疾病发病有关[1]。我们探讨了血清尿酸水平升高与缺血性心脏病及扩张型心肌病慢性心衰的左心室收缩和舒张功能的相关性。对象与方法1.对象选择2002年2月～2004年10月住院的慢性心衰患者90例,男58例,女32例,年龄30～76岁,平均年龄54.2岁±6.6岁。缺血性心脏病组45例,扩张型心肌病组45例。两组间年龄、性别等一般临床资料比较无差异。入选病例诊断标准:(1)左心室射血分数<0.45;心衰病程≥6个月。(2)缺血性心肌病符合目前公认的诊断标准[即三个肯定条件:①有明确…     

铁在缺血性心脏病中的作用研究进展

铁催化羟自由基生成，介导脂质过氧化作用增加，使氧化型低密度脂蛋白（Ox-LDL)生成增多，这是造成AS损伤的一个重要过程。认为铁储存水平升高是缺血性心脏病的一种重要危险因子。     

卡维地洛与美托洛尔治疗缺血性心脏病心力衰竭的疗效观察

目的:观察卡维地洛和美托洛尔对缺血性心脏病心力衰竭患者的临床疗效。方法:缺血性心脏病心力衰竭患者80例,左室射血分数（LVEF）≤0.45,心功能（NYHA）ⅡⅣ级,常规治疗基础上随机分为卡维地洛组和美托洛尔组,治疗3月后,观察两种药物对心功能及运动耐量的影响。应用心脏彩色超声仪测定心功能基线值及3月后的变化。用6 m in步行距离测定运动耐量的改善程度。结果:经过3月的治疗,卡维地洛组与美托洛尔组心率、血压、运动耐量改善程度及心功能均有明显改善,且卡维地洛组6 m in步行试验结果,收缩压、舒张压变化及左室收缩末容积（LVESV）、左室舒张末容积（LVEDV）、LVEF改善程度明显优于美托洛尔组（P<0.01）。结论:在常规治疗基础上卡维地洛、美托洛尔对缺血性心脏病的治疗均有显著效果,前者在改善运动耐量、LVEDV、LVESV及心室射血方面更优。     

Increased ventricular sialylation in patients with heart failure secondary to ischemic heart disease

Background: Elevated serum sialic acids are associated with increased cardiovascular mortality, but sialic acid levels have not been studied in cardiac tissue. Methods: Myocardial samples were obtained at the time of transplantation from 23 patients (age 54 ± 12 years) with heart failure secondary to ischemic heart disease and 16 patients (age 51 ± 7 years) with idiopathic dilated cardiomyopathy (DCM). A control group comprised postmortem samples obtained from 14 patients (age 70 ± 5 years) who died of non-cardiovascular causes. Ventricular sialylation was quantitated using the sialic acid-specific lectins Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA) using a chemiluminescence assay. Results are expressed as the percentage (± standard error of the mean) of the binding of lectin to a standardized control sample of human myocardium. Results: Ventricular sialylation recognized by MAA was 55 ± 7% in patients with heart failure secondary to ischemic heart disease compared with 26 ± 7% for DCM (p = 0.006) and 32 ±8% for controls (p = 0.04), and that recognized by SNA was 69 ± 7% in patients with heart failure secondary to ischemic heart disease compared with 42 ± 6% for DCM (p = 0.006) and 38 ± 7% for controls (p = 0.006). No significant difference in ventricular sialylation was observed between patients with DCM and controls. Conclusion: Myocardial levels of sialic acids are significantly increased in patients with heart failure secondary to ischemic heart disease compared with patients with idiopathic dilated cardiomyopathy and controls. Our findings are important in view of recent reports of an association between serum sialic acid concentration and cardiovascular mortality and require further investigation.     

β3肾上腺素受体介导的脂解作用与缺血性心衰的关系（英文）

β3肾上腺素受体（β3AR）是新发现的受体,主要参与脂肪组织甘油三酯的降解,产生能量;心衰时心脏中β3AR上调;心肌缺血缺氧时,内源性脂解作用可维持心肌的收缩性;为了维持心功能慢性缺血性心衰代偿期很可能存在能量代谢重建:在神经内分泌激活的同时,以外源性游离脂肪酸（FFA）为主要能量底物,心脏缺血缺氧进一步加重时,β3AR代偿性上调并介导心肌细胞的内源性脂解供能,葡萄糖经由3-磷酸甘油参与合成内源性三酰甘油再脂解而间接供能,葡萄糖的氧化被抑制,此时心肌细胞兼有类似脂肪细胞的功能。心衰时β3AR上调是能量代谢代偿的结果。但上调的β3AR长期过度激活有可能引起心肌组织继发性肉碱缺乏,导致ATP生成障碍使心衰失代偿,因而在心衰失代偿期β3AR阻滞剂可能有利于缓解心衰。而（β3AR激动药最终表现为正性肌力作用还是负性肌力作用,要看在具体的作用部位它对β3AR的直接效应与其对胰岛素的继发效应二者的力量对比）。从理论上讲,β3AR激动药用于慢性缺血性心衰代偿期,既可改善心肌的能量代谢,产生正性肌力作用,又可降低动脉血压,降低心脏的前负荷,从而改善心功能;β3AR激动药还可改善与心衰并存的胰岛素抵抗。心脏能量代谢的缺陷越来越被认为在心衰的进展中起着重要的决定性作用,心脏的代谢适应和适应不良是很有前景的药物治疗新靶点。     

Relationship between circulating endothelial progenitor cells and insulin resistance in non-diabetic patients with ischemic chronic heart failure

AimThe objective of this study was to assess a relationship between insulin resistance (IR) and counts of CD45⁻CD34⁺, CD14⁺CD309⁺, and CD14⁺CD309⁺Tie2⁺ phenotyped circulating endothelial progenitor cells (EPCs) in patients with ischemic chronic heart failure (CHF).MethodsThe study involved 300 CHF patients (186 males) aged 48–62 years with angiografically proven coronary artery disease and/or previously defined myocardial infarction. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). EPC populations were phenotyped by flow cytofluorimetry.ResultsCirculating EPCs counts were statistically significantly lower in CHF patients with IR than in patients without IR. We found that the most valuable multivariable predictors of the depletion of the CD45⁺CD34⁺ EPCs were NT-pro-brain natriuretic peptide (BNP) (1.32; 95% CI = 1.19–2.77; P = 0.001), left ventricular ejection fraction (OR = 1.30; 95% CI = 1.09–1.60; P = 0.002), NYHA class (OR = 1.12; 95% CI = 1.02–1.19; P = 0.001). NT-pro-BNP (OR = 1.45; 95% CI = 1.15–2.90; P = 0.003), left ventricular ejection fraction (OR = 1.32; 95% CI = 1.11–1.65; P = 0.001) were found as powerful predictors for depletion in CD45⁻CD34⁺ EPCs. We also identified six independent variables with high predictive value for depletion of CD14⁺CD309⁺ EPCs: NT-pro-BNP (OR = 1.41; 95% CI = 1.15–2.90; P = 0.003), left ventricular ejection fraction (OR = 1.18; 95% CI = 1.10–1.76; P = 0.036), NYHA class (OR = 1.15; 95% CI = 1.07–1.22; P = 0.001), hs-C reactive protein (OR = 1.02; 95% CI = 1.01–1.05; P = 0.012). As independent multivariable predictors for depletion in CD14⁺CD309⁺Tie2⁺ EPCs were selected five variables: NT-pro-BNP (OR = 1.65; 95% CI = 1.44–4.70; P = 0.006), left ventricular ejection fraction (OR = 1.07; 95% CI = 1.02–1.12; P = 0.018), NYHA class (OR = 1.13; 95% CI = 1.06–1.21; P = 0.001), hs-C-reactive protein (OR = 1.08; 95% CI = 1.03–1.16; P = 0.002).ConclusionIR may be an additional factor contributing decreased circulating level of proangiogenic EPCs in non-diabetic CHF patients.     

雌激素与缺血性心脏病

以往的临床观察证实 ,生育年龄的女性缺血性心脏病的发病率和死亡率明显低于同龄男性。绝经后的妇女服用雌激素与不服用雌激素相比 ,前者心脏病事件少于后者。尽管临床的观察结果还有争议 ,越来越多的临床前期研究表明 ,雌激素对缺血性心脏病具有保护作用。研究结果显示 ,雌激素和其受体调节器是通过减少炎性反应在缺血/再灌注引起心肌损伤时起保护作用的。本文作者就近年的一些研究结果作一综述 ,并就雌激素替代治疗处理心肌缺血及再灌注损伤进行探讨。     

Melatonin protects against ischemic heart failure in rats

Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an important role in heart failure. Melatonin is thought to have antiatherogenic, antioxidant, and vasodilatory effects. In this study, we investigated whether melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF was induced by left anterior descending (LAD) coronary artery ligation and rats were treated with either vehicle or melatonin (10 mg/kg) for 4 weeks. At the end of this period, echocardiographic measurements were recorded and the rats were decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lysosomal enzymes (β‐D‐glucuronidase, β‐galactosidase, β‐D‐N‐acetyl‐glucosaminidase, acid phosphatase, and cathepsin‐D) were studied in plasma samples, while malondialdehyde and glutathione levels and Na+, K+‐ATPase, caspase‐3 and myeloperoxidase activities were determined in the cardiac samples. Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin‐3 levels in cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin‐3 levels were also determined by histological analyses. In the vehicle‐treated HF group, cardiotoxicity resulted in decreased cardiac Na+, K+‐ATPase and SERCA activities, GSH contents and caveolin‐3 levels, while plasma LDH, CK, and lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities were found to be increased. On the other hand, melatonin treatment reversed all the functional and biochemical changes. The present results demonstrate that Mel ameliorates ischemic heart failure in rats. These observations highlight that melatonin is a promising supplement for improving defense mechanisms in the heart against oxidative stress caused by heart failure.     

Effect of aprindine on heart rate variability indices in patients with ischemic heart disease

BACKGROUND: Decreased heart rate variability indices (HRV) are associated with untoward outcome of patients with ischemic heart disease (IHD). Most class I antiarrhythmic agents decrease HRV, but aprindine (a new class I antiarrhythmic agent) is reported to increase HRV in patients without ischemia. HYPOTHESIS: The study was undertaken to determine whether apridine might increase HRV in patients with IHD. METHODS: To investigate the effect of aprindine on HRV in patients with IHD, we performed 24-h ambulatory electrocardiogram (ECG) at the end of placebo and aprindine (60 mg daily) treatment phases on 38 patients with IHD and at least isolated premature ventricular contractions (PVC). The study protocol utilized a single blind, 4-week, placebo-controlled design. Heart rate variability from ambulatory ECG included SDNN (ms), SDANN (ms), SD (ms), rMSSD (ms), pNN50 (%); frequency analysis of HRV consisting of total (ms, 0.01-1.00 Hz), low (ms, 0.04-0.15 Hz), and high (ms, 0.15-0.40 Hz) components. RESULTS: Study patients were divided into three groups according to the severity of IHD and antiarrhythmic efficacy of aprindine. Group 1 consisted of 15 patients with angina with single-vessel disease, and Group 2 was composed of 10 patients with either multivessel disease or post myocardial infarction; PVCs decreased in both groups as result of aprindine treatment. Group 3 consisted of 13 patients who showed no decreased PVC after aprindine treatment. RMSSD increased, and pNN50 and high-frequency spectra tended to increase in Group 1, while SD, rMSSD, pNN50, and total and low-frequency spectra decreased in Group 3; no significant changes were observed in Group 2. Aprindine significantly augments vagal activity, as reflected by the increase of rMSSD, pNN50, and high-frequency spectra in mild IHD. CONCLUSION: These salutary effects are less in more severe IHD, but aprindine does not aggravate HRV. Thus, if there are salutary effects on arrhythmias and no proarrhythmic effects, aprindine could be prescribed to patients with IHD without concern about decreasing HRV.     

Stress Doppler echocardiography in the evaluation of ischemic heart disease

Doppler echocardiography enables convenient, noninvasive evaluation of global, systolic performance at rest and during exercise. Early studies suggested that Doppler parameters of systolic function were sensitive to exercise-induced myocardial ischemia and could identify patients with severe coronary artery disease. Subsequent investigation, however, has identified several factors in addition to myocardial ischemia that can significantly influence exercise Doppler study results. Thus, in order to obtain reliable information, the many factors that can influence Doppler measurements of aortic flow velocity and acceleration must be accounted for. Further work in this area is likely to produce results that encourage greater application of this technique in experimental and clinical research. At present, the role of stress Doppler echocardiography in the evaluation of ischemic heart disease remains uncertain.     

干细胞治疗缺血性心脏病的分子影像评价

缺血性心脏病(IHD)是目前世界范围内致病和致死的主要原因之一,干细胞(SC)作为一项潜在的治疗手段,成为当今实验室研究的热点,然而在研究过程中,遇到诸多问题:如SC在体的存活率不高及功能发挥不理想等。分子影像,包括多种多样的成像技术,一方面可以非侵入性的观察细胞,另一方面通过较长时间追踪细胞的转归和分化情况,指导优化SC治疗效果。本文将从以下3个方面介绍近年来在分子影像技术SC治疗IHD上的进展及突破:SC移植后在体内存活增殖的分子影像评估;移植SC在体功能的分子成像;针对SC治疗安全性的分子成像。最后,我们对分子影像的应用提出设想和展望。     

Increased circulating endothelial cells in acute heart failure: comparison with von Willebrand factor and soluble E-selectin

BACKGROUND: Circulating endothelial cells (CECs) in the peripheral blood, probably representing the most direct evidence of endothelial cell damage, are increased in myocardial infarction, unstable angina and critical limb ischaemia. As chronic heart failure is also associated with endothelial abnormalities, we hypothesised that CECs are raised in acute heart failure and that they would correlate with plasma indices of endothelial perturbation, that is, von Willebrand factor (vWf) and soluble E-selectin. METHODS: We studied 30 patients with acute heart failure (venesected within 24 h of emergency hospital admission), 30 patients with chronic stable heart failure (venesected as out-patients, all patients in sinus rhythm with ejection fraction < or = 40%) and 20 healthy controls. CECs were quantified using epifluorescence microscopy after CD146-immunomagnetic separation and phenotyped by streptavidin/biotin immunocytochemistry. Citrated plasma was analysed for soluble E-selectin and vWf by ELISA. RESULTS: Levels of CECs, vWf and soluble E-selectin were significantly higher (all p<0.01) in patients with heart failure compared to controls, with no significant differences between acute and chronic heart failure. CECs correlated with plasma vWf (p<0.0001) and soluble E-selectin (p = 0.022) but not ejection fraction or NYHA class. In multiple regression analysis, heart failure was the only independent predictor of raised CECs (p<0.0001). Immunoperoxidase-defined surface expression of CD34, CD45 and CD36 by CECs was <2%, 0% and 8%, respectively. CONCLUSION: CECs, a possibly heterologous population, may be used as a novel measure of endothelial damage in acute heart failure and may have implications for the thrombotic risk associated with acute and chronic heart failure and prognosis in this condition.