Evidence of increased oxidative stress by simple measurements in patients with dilated cardiomyopathy

The heart cannot supply sufficient blood for tissue metabolic needs in patients with congestive heart failure. Hypoxia and organ hypoperfusion increase oxidative activity. It has been reported that free radicals are involved in the genesis of heart failure. The aim of this study was to assess the status of oxidative stress by simple measurements in patients with dilated cardiomyopathy of ischemic or idiopathic etiology. Eleven patients (8 M, 3 F, age range 32 to 65 years) with dilated cardiomyopathy of ischemic etiology and 12 patients (8 M, 4 F, age range 31 to 66 years) with dilated cardiomyopathy of idiopathic etiology were included in the study. A control group included 21 healthy subjects (12 M, 9 F, age range 25 to 67 years). Levels of thiobarbituric acid-reactive substances, total thiols, and fluorescent products of lipid peroxidation were measured in plasma/serum samples of patients and controls. No statistically significant differences were found between the two patient groups for the parameters studied (p>0.05). Levels of thiobarbituric acid-reactive substances and fluorescent products of lipid peroxidation were higher in both patient groups than in controls (p<0.05), whereas concentrations of total thiols were decreased (p<0.05). In conclusion, in patients with idiopathic or ischemic dilated cardiomyopathy, there are associated abnormalities of a range of markers of increased oxidative stress and lipid peroxidation. The plasma/serum constituents studied can be routinely measured in order to monitor patients during antioxidant therapy.     

Acute onset of severe dilated cardiomyopathy during bromocriptine therapy

OBJECTIVE: To report a case of severe dilated cardiomyopathy (DCMP) in a patient on bromocriptine therapy for a microprolactinoma. CASE SUMMARY: A 31-year-old African American female, who had been receiving bromocriptine 5 mg orally daily for a microprolactinoma during the preceding month, developed severe DCMP. An echocardiogram showed a markedly dilated left ventricle with severe reduction in the left-ventricular ejection fraction in the absence of any other identifiable causes of DCMP such as a peripartum state, ethanol use, preceding systemic viral illness, chronic hypocalcemia, chronic hypophosphatemia, or chronic uncontrolled tachycardia. She improved substantially (both symptomatically and echocardiographically) after cessation of bromocriptine therapy and initiation of supportive treatment of congestive heart failure (CHF). She showed no recurrence of CHF at a follow-up visit 2 months after withdrawal of the supportive care. The patient was not rechallenged with bromocriptine due to the clinical/ethical gravity of this probable adverse effect. DISCUSSION: Although cardiopulmonary adverse effects have been reported with the use of cabergoline (another dopamine agonist), to the best of our knowledge, this is the first case report of severe life-threatening DCMP associated with bromocriptine therapy. Causality assessment using the Naranjo probability scale revealed that the adverse drug event was probable. CONCLUSIONS: Bromocriptine was probably associated with DCMP in a patient being treated for a microprolactinoma. Severe DCMP needs to be considered a potentially life-threatening but reversible adverse effect of bromocriptine therapy for microprolactinoma of the pituitary gland.     

Effects of sesame oil on oxidative stress after the onset of sepsis in rats

The aim of this study was to investigate effects of sesame oil on oxidative stress after the onset of sepsis in rats. Effects of sesame oil on lipid peroxidation, superoxide anion, superoxide dismutase, catalase, glutathione, and nitrite after the onset of endotoxin intoxication were determined. To further examine the protective effect of sesame oil on sepsis, a mortality study was also conduced in cecal ligation and puncture-induced sepsis in rats. Sesame oil was given orally 6 h after endotoxin administration and cecal ligation and puncture, and parameters were then measured in another 6 h. Data demonstrated that a single dose of sesame oil reduced lipid peroxidation 6 h after endotoxin intoxication. Superoxide anion counts were decreased, glutathione levels were increased, and activities of superoxide dismutase and catalase, as well as nitrite levels, were not altered in lipopolysaccharide plus sesame oil-treated groups compared with lipopolysaccharide-treated groups. Furthermore, sesame oil given 6 h after cecal ligation and puncture significantly increased survival rate. Thus, we suggested that sesame oil could be used as a potent antioxidant to reduce oxidative stress after the onset of sepsis in rats.     

Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy

Background: Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood. Methods and results: We studied 99 patients with IDC (age 54 ± 1 years, left ventricular ejection fraction (EF) 40 ± 1%, maximum oxygen uptake (VO₂max) 20 ± 1 ml kg^?1 min^?2, mean ± SEM) by using ¹²³I‐metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)‐ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)‐6 and N‐terminal B‐type natriuretic peptide (NT‐proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL‐6 (r = 0·42, P<0·001 and r = ?0·31, P<0·01) and NT‐proBNP (r = 0·48, P<0·001 and r = ?0·40, P<0·001). During a median follow‐up of 4·1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter–defibrillator). In these patients, MIBG washout was higher (53 ± 4 versus 40 ± 2%, P = 0·01) and H/M ratio lower (1·38 ± 0·04 versus 1·51 ± 0·02, P = 0·01) than in patients without an event. Conclusions: In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.     

Effects of insulin treatment on endoneurial and systemic oxidative stress in relation to nerve conduction in streptozotocin-diabetic rats

As increased oxidative stress is probably a pathogenetic factor in the development of diabetic complications, we studied nerve function and endogenous antioxidants in plasma, erythrocytes and sciatic nerve of untreated and insulin-treated streptozotocin-diabetic rats. After 18 weeks, the diabetes-induced sciatic nerve conduction velocity deficits were approximately 65% improved by insulin ( P <0.001). Plasma superoxide dismutase was significantly reduced in diabetes ( P <0.01); smaller decreases in plasma catalase and glutathione levels were observed. These changes were corrected by insulin treatment. In erythrocytes, decreased superoxide dismutase ( P <0.05) and increased total glutathione levels ( P <0.05) were found. All effects of diabetes, including a rise in plasma malonyldialdehyde ( P <0.05), were partially reversed by insulin treatment. In nervous tissue, diabetes caused increased catalase activity, uninfluenced by insulin ( P <0.05). Nerve superoxide dismutase and glutathione did not change. The data suggest that, in diabetes, changes in systemic rather than endoneurial oxidative stress lead to nerve dysfunction.     

Cardiac resynchronisation therapy response predicts occurrence of atrial fibrillation in non-ischaemic dilated cardiomyopathy

Aim: The aim of this study was to determine whether or not cardiac resynchronization therapy (CRT) has a favourable effect on the incidence of new‐onset atrial fibrillation (AF) in a homogeneous population of patients with non‐ischaemic idiopathic‐dilated cardiomyopathy and severe heart failure. Methods: We designed a single‐centre prospective study and enrolled 58 patients AF naïve when received CRT. After 1 year of follow‐up our population was subdivided into responders (72.4%) and non‐responders (27.6%), so as to compare the incidence of AF after 1, 2 and 3 years of follow‐up in these two groups. Results: Already after 1 year, there was a significant (p < 0.05) difference in new‐onset AF in non‐responder patients with respect to responders (18.2% vs. 3.3%). These data were confirmed at 2 years (33.3% vs. 12.2%) and 3 years (50.0% vs. 15.0%) follow‐up. In particular, 3 years after device implantation non‐responders had an increased risk to develop new‐onset AF (OR = 5.67). Conclusions: This is the first study analysing long‐term effects of CRT in a homogeneous population of patients with non‐ischaemic dilated cardiomyopathy, indicating the favourable role of this non‐pharmacological therapy on the prevention of AF.     

Factors affecting onset of ventricular arrhythmias and sudden death in patients with dilated cardiomyopathy

The study of 46 patients suffering from dilated cardiomyopathy has shown that both ventricular tachycardias detected at 24-h ECG monitoring and late ventricular potentials are essential predictors of sudden arrhythmic death. These predictors depend neither on severity of left ventricular systolic and diastolic dysfunction nor on severity of cardiac decompensation.     

超声心动图在大鼠扩张型心肌病模型建立中的应用价值

目的探讨经胸超声心动图评价大鼠扩张型心肌病模型的价值。方法取10周龄雄性SD大鼠40只。随机分为4组:对照组和阿霉素低、中、高剂量组,经腹腔注射阿霉素累计量分别为0、8、16、24mg/kg,于0、2、4、6、8周先后行超声心动图检查;第9周行血流动力学、心肌组织病理学检查。结果超声心动图观察到随着阿霉素剂量的累积,大鼠左室舒张末径进行性增大,射血分数逐渐下降。8周时中剂量组左室舒张末径由(6.79±0.62)mm增加至(7.24±0.23)mm,射血分数由(92±2)%下降至(82±3)%(均P<0.05);高剂量组左室舒张末径由(6.84±0.39)mm增加至(7.67±0.08)mm,射血分数由(92±2)%下降至(79±1)%(均P<0.01)。血流动力学检查显示中、高剂量组左心室压峰值、左室压力最大上升及下降速度明显下降(均P<0.01)。组织病理检查显示中、高剂量组心肌损伤严重。而对照组、阿霉素小剂量组上述指标均无显著改变。结论经胸超声心动图可无创、准确、敏感地动态监测大鼠扩张型心肌病模型心腔及心功能的变化,有推广应用的价值。     

Advances in the treatment of dilated cardiomyopathy

The nursing care of the patient with dilated cardiomyopathy focuses on (1) improving right and left heart function, i.e., titrating vasoactive drugs to maintain acceptable cardiac index with minimum side effects (and/or monitoring the operation of a left ventricular assist device when left heart function is refractory to vasoactive drugs), (2) reducing cardiac filling pressures with diuretics, vasodilators, and/or restriction of dietary sodium, oral and IV fluids, (3) maintaining optimum oxygenation, (4) preventing complications associated with either the disease or treatment, and (5) assisting the patient/family to maintain hope during the often lengthy and crisis-filled wait for a donor heart. The critical care nurse is challenged, often for weeks or months at a time, by the complexity of this patient's physical and emotional needs and functions in a collaborative role with the entire health team in an attempt to maintain both cardiovascular and psychological stability until a donor heart is available.     

心脏MR特征追踪技术定量评估扩张型心肌病左心房心肌应变

目的 观察心脏MR特征追踪（CMR-FT）技术定量分析扩张性心肌病（DCM）左心房（LA）心肌应变的价值。方法 对28例临床诊断DCM患者（DCM组）及23名健康对照者（对照组）采集心脏MRI。采用CVI42后处理软件,以CMR-FT技术基于两腔心和四腔心图像获得LA应变参数,测量LA容积（LAV）参数;比较组间CMR参数的差异,分析DCM的LA应变参数与LA射血分数（LAEF）、氨基末端脑钠肽前体（NT-pro-BNP）的相关性。结果 相比对照组,DCM组LAV增大、LAEF减小,应变和应变率参数总应变（εs）、被动应变（εe）、主动应变（εa）、左心室收缩期峰值正向应变率（SRs）、左心室舒张早期LA峰值负向应变率（SRe）及左心室舒张晚期LA峰值负向应变率（SRa）绝对值均减小（P均<0.05）。DCM患者εs与LA总射血分数（LAEF_total）、εe与LA被动射血分数（LAEF_passive）及εa与LA主动射血分数（LAEF_active）均呈高度正相关（r=0.92、0.86、0.86,P均<0.05）,εs、εe、εa与NT-Pro-BNP均呈中度负相关（r=-0.49、-0.40、-0.44,P均<0.05）。结论 CMR-FT技术可评估DCM患者LA心肌应变,有助于定量分析其LA功能;DCM所致LA应变参数降低与容积参数及NT-pro-BNP相关。     

Dobutamine stress echocardiography in prediction of dilated cardiomyopathy in patients with allergic myocarditis]

Total contractility reserve (TCR) and role of TCR in prediction of dilated cardiomyopathy (DCM) were evaluated in patients with infectious allergic myocarditis (IAM) by means of stress-echocardiography with dobutamine. Systolic function of the left ventricle (LV) appeared activated in different degree in relatively equal baseline low levels of LV contractility. IAM patients with reduced reserve of TCR are characterized by low increment of LV contractility under stress test and frequent onset of DCM. The increment of ejection fraction in low-dose dobutamine stress echocardiography was found informative in prediction of DCM development, highly sensitive and specific.     

骨髓间充质干细胞移植治疗大鼠扩张型心肌病

背景：扩张型心肌病所致的心肌纤维化是心力衰竭的病理基础,目前药物治疗、介入治疗和外科手术均不能替代坏死心肌和彻底改善心脏功能。目的：观察异体骨髓间充质干细胞移植对大鼠扩张型心肌病心脏功能的作用和心肌纤维化的影响。方法：40只Wistar大鼠随机数字表法分为细胞移植组（n=15）、对照组（n=15）和空白组（n=10）,前2组建立大鼠扩张型心肌病模型。造模成功4周后细胞移植组注射骨髓间充质干细胞悬液150μL（含3×106个细胞）,对照组和空白组注射等量培养液。结果与结论：与空白组相比,细胞移植组和对照组移植前左室收缩末期内径增加,射血分数和缩短分数明显下降（P〈0.01）;移植后4周,细胞移植组超声心动图检查和移植前相比,左室收缩末期内径下降、射血分数和缩短分数明显升高（P〈0.01）。细胞移植组心脏胶原的表达低于对照组（P〈0.05）。与对照组相比,其他2组基质金属蛋白酶2及基质金属蛋白酶9表达明显下降（P〈0.05）。提示骨髓间充质干细胞移植后可改善心肌纤维化及扩张型心肌病鼠的心脏功能。     

Mutations of the dystrophin gene in dilated cardiomyopathy

X-linked dilated cardiomyopathy(XLDCM) is caused by mutations of the dystrophin gene, which was originally cloned as the responsible gene for Duchenne muscular dystrophy and Becker muscular dystrophy. Mutations due to XLDCM are centered on 5' end of the gene, especially M-promoter and the adjacent region. However, other mutations are dispersed and cannot be characterized. Three mechanisms have been proposed by which the involvement of cardiac muscle is so severe in spite of the lack of skeletal muscle symptoms; 1) up-regulation of B- and P-dystrophin in merely skeletal muscle compensating for the defect of M-dystrophin, 2) dysfunction of some parts of dystrophin specifically essential to cardiac muscle, 3) different expression patterns of mutant mRNA between cardiac and skeletal muscle.     

原发性扩张型心肌病的电子束CT表现

目的:评价电子束CT对原发性扩张型心肌病诊断及鉴别诊断的价值。材料与方法:对9例经临床及影象学诊断的扩张型心肌病患者行电子束CT扫描。结果:左心室扩张8例,均有室壁运动普遍减弱,LVEDV235±103ml,LVEF20.3％±7.3％;右心室扩张伴运动减弱1例。结论:电子束CT能全面反映扩张型心肌病的病理及功能改变,可作为扩张型心肌病诊断的手段。     

Activation of the complement system in dilated cardiomyopathy

The levels of anaphylatoxins (C3a, C5a) in blood, components of complements C3 and C4, antibodies to cardiolipin, IgG, IgA, IgM, IgE and circulating immune complexes were measured in 21 patients with dilated and hypertrophic cardiomyopathy (DCMP and HCMP) and in 11 donors. The mean level of C3a in DCMP patients (572 +/- 55 ng/ml) was significantly higher than in HCMP patients (344 +/- 30 ng/ml) and in donors (294 +/- 43 ng/ml) (p less than 0.001). On comparison of C5a concentrations in DCMP patients (2.2 +/- 0.52 ng/ml), HCMP patients (3.3 +/- 1.2 ng/ml) and in donors (1.6 +/- 0.82 ng/ml) no significant differences were found (p greater than 0.05). It has been established that in the group of DCMP patients with thromboembolic complications, the concentrations of C3a (736 +/- 95 ng/ml) were significantly higher than in those without such complications (334 +/- 14 ng/ml) (p less than 0.001). The data obtained permit discussing the role of anaphylatoxins in the development of thromboembolic complications in DCMP patients.     

扩张型心肌病相关基因的研究与进展

目的：分析基因突变与扩张型心肌病发病的可能关系。 资料来源：应用计算机检索Pubmed及English Medcal Current Contents（EMCC）数据库1998-01／2005-11关于基因突变与扩张型心肌病的文献，检索词为“dilated cardiomyopathy，gene，mutation”，语言种类为English。同时检索Chinese Medical Current Contents（CMCC）数据库2000-01／2005-11有关扩张型心肌病遗传学研究的文献，检索词为“扩张型心肌病，基因，突变”，并限定语言种类为中文。 资料选择：对检索结果进行初审，选取基因突变与扩张型心肌病方面的相关信息进行整理，筛除明显不相关的或针对性不强的文章。同一领域的文章则选择近期发表或权威杂志文章。 资料提炼：进一步整理分析所选的37篇文献，筛除重复的研究或Meta分析，最后选择符合标准的20篇文章作为参考文献。 资料综合：扩张型心肌病是一种多病因、多因素的心肌疾病，其发病与病毒感染、自身免疫反应、细胞凋亡及遗传因素等相关。近年来，研究表明遗传因素在其发病中起着重要作用，国内外学者发现了许多与扩张型心肌病相关的基因突变，这些突变主要位于细胞骨架蛋白编码基因、肌小节蛋白编码基因及线粒体DNA等。 结论：基因突变在扩张型心肌病的发病中起着重要作用，突变基因的检测将有利于扩张型心肌病的早期诊断、早期预防及特定基因个性化治疗。但目前仍有许多实际问题有待进一步探讨。     

扩张型心肌病相关基因的研究与进展

目的:分析基因突变与扩张型心肌病发病的可能关系。资料来源:应用计算机检索Pubmed及EnglishMedicalCurrentContents(EMCC)数据库1998-01/2005-11关于基因突变与扩张型心肌病的文献,检索词为“dilatedcardiomyopathy,gene,mutation”,语言种类为English。同时检索ChineseMedicalCurrentContents(CMCC)数据库2000-01/2005-11有关扩张型心肌病遗传学研究的文献,检索词为“扩张型心肌病,基因,突变”,并限定语言种类为中文。资料选择:对检索结果进行初审,选取基因突变与扩张型心肌病方面的相关信息进行整理,筛除明显不相关的或针对性不强的文章。同一领域的文章则选择近期发表或权威杂志文章。资料提炼:进一步整理分析所选的37篇文献,筛除重复的研究或Meta分析,最后选择符合标准的20篇文章作为参考文献。资料综合:扩张型心肌病是一种多病因、多因素的心肌疾病,其发病与病毒感染、自身免疫反应、细胞凋亡及遗传因素等相关。近年来,研究表明遗传因素在其发病中起着重要作用,国内外学者发现了许多与扩张型心肌病相关的基因突变,这些突变主要位于细胞骨架蛋白编码基因、肌小节蛋白编码基因及线粒体DNA等。结论:基因突变在扩张型心肌病的发病中起着重要作用,突变基因的检测将有利于扩张型心肌病的早期诊断、早期预防及特定基因个性化治疗。但目前仍有许多实际问题有待进一步探讨。     

Apheresis in the treatment of idiopathic dilated cardiomyopathy

Dilated cardiomyopathy (DCM) causes significant morbidity and mortality and is the number one indication for cardiac transplantation in the United States. A large percentage of cases of DCM have no identifiable cause with evidence suggesting that these may represent an autoimmune disorder triggered by viral myocarditis. There is a growing body of literature suggesting that a number of immunoadsorption techniques, as well as plasma exchange, may have a role in the treatment of idiopathic DCM. The hypothesized autoimmune mechanism behind idiopathic DCM as well as the published evidence for the use of apheresis in this disorder are reviewed. The available evidence suggests that apheresis may be an effective treatment, but additional research is needed to identify markers that will predict response and the most effective apheresis technique. J. Clin. Apheresis 2012. © 2012 Wiley Periodicals, Inc.     

Cardiac resynchronization therapy in a case of myotonic dystrophy (Steinert's disease) and dilated cardiomyopathy

Steinert's disease (Dystrophia myotonica type 1) is an autosomal dominant neuromuscular disease characterized by myotonia, muscle weakness, frontal balding, cataracts, cardiac conduction abnormalities, especially long PR interval and wide QRS complex. Although subclinical mild myocardial dysfunction may be detected in this syndrome, overt myocardial dysfunction with heart failure called as "myotonic heart disease" is not frequent. Cardiac resynchronization therapy is an effective treatment modality to improve morbidity and mortality in patients with intraventricular conduction delay and congestive heart failure. We report improvement of cardiac dyssynchrony and symptoms of heart failure with biventricular pacing in a 37-year-old male patient with overt myotonic heart disease, PR segment prolongation, and complete left bundle branch block.