Effects of myosin heavy chain manipulation in experimental heart failure

The myosin heavy chain (MHC) isoforms, α- and β-MHC, are expressed in developmental- and chamber-specific patterns. Healthy human ventricle contains ∼ 2-10% α-MHC and these levels are reduced even further in the failing ventricle. While down-regulation of α-MHC in failing myocardium is considered compensatory, we previously demonstrated that persistent transgenic (TG) α-MHC expression in the cardiomyocytes is cardioprotective in rabbits with tachycardia-induced cardiomyopathy (TIC). We sought to determine if this benefit extends to other types of experimental heart failure and focused on two models relevant to human heart failure: myocardial infarction (MI) and left ventricular pressure overload. TG and nontransgenic rabbits underwent either coronary artery ligation at 8 months or aortic banding at 10 days of age. The effects of α-MHC expression were assessed at molecular, histological and organ levels. In the MI experiments, we unexpectedly found modest functional advantages to α-MHC expression. In contrast, despite subtle benefits in TG rabbits subjected to aortic banding, cardiac function was minimally affected. We conclude that the benefits of persistent α-MHC expression depend upon the mechanism of heart failure. Importantly, in none of the scenarios studied did we find any detrimental effects associated with persistent α-MHC expression. Thus manipulation of MHC composition may be beneficial in certain types of heart failure and does not appear to compromise heart function in others. Future considerations of myosin isoform manipulation as a therapeutic strategy should consider the underlying etiology of cardiac dysfunction.     

内皮素对大鼠培养心肌细胞肥大及肌球蛋白基因表达影响的研究

为探讨内皮素（ET）在大鼠培养心肌细胞肥大及肌球蛋白（MHC）基因表达中的作用，采用心肌细胞培养及斑点杂交的方法，同时测定心肌细胞直径、数目及3H亮氨酸（3H－Leu）掺入率，观察ET耐心肌细胞肥大及肌球蛋白基因表达的影响。结果显示：ET（10-7mol／L）作用培养心肌细胞24h后，细胞直径明显增大（P＜0．01），细胞数目无明显增加（P＞0．05）；不同浓度ET（10－10～10－7mol／L）可刺激心肌细胞3H－Leu掺入率呈明显剂量依赖性增加；随ET浓度（10－9～10－7mol／L）增高，β-肌球蛋白重链（β-MHC）mRNA表达呈剂量依赖性增加，α－MHCmRNA表达相应减少。提示：①ET可促进心肌细胞肥大，而不诱导心肌细胞增殖;②ET促使心肌细胞由α-MHC向β-MHC转化，说明ET促心肌细胞肥大是病理性的，此作用发生在翻译前水平。     

一氧化氮对内皮素促心肌细胞肥大及肌球蛋白基因表达的影响

目的 :探讨一氧化氮 (NO )对内皮素 (ET)促大鼠培养心肌细胞肥大及肌球蛋白重链 (MHC)基因表达的影响。方法 :对 12 0只大鼠采用心肌细胞培养及斑点杂交的方法 ,同时测定心肌细胞直径、数目及 3H-亮氨酸(3H- L eu)掺入率。结果 :NO组、ET组心肌细胞数目与对照组比较 ,均无明显差异 (P >0 .0 5 ) ,ET组细胞直径较对照组增加 (34 .5± 5 .5 ) % (P <0 .0 1) ,NO组较对照组增加 (6 .2± 2 .5 ) % (P >0 .0 5 ) ;NO明显抑制 ET促 3H-L eu掺入率的增加 (P <0 .0 1) ,NO组与对照组相比 ,β- MHC m RNA表达明显增加 ,α- MHC m RNA表达明显减少 (P <0 .0 1) ,NO显著逆转 ET的上述作用。结论 :NO有抑制 ET促心肌细胞肥大的作用 ,并可逆转 ET致MHC同工蛋白的病理性转换     

苦参碱对去甲肾上腺素促心肌细胞肥大及肌球蛋白重链基因表达的影响

目的 :探讨苦参碱对去甲肾上腺素 (NE)促心肌细胞肥大及肌球蛋白重链 (MHC)基因表达作用的影响。方法 :采用测定心肌细胞直径、数目 ,3 H 亮氨酸 (3 H Leu)掺入率及分子杂交的方法 ,观察NE对大鼠培养心肌细胞肥大及MHC基因表达的影响 ,并用苦参碱治疗。结果 :NE显著促进心肌细胞直径增大 (P <0 .0 5 )及3 H Leu掺入率的增加 (P <0 .0 1) ,并诱导心肌细胞 β MHC基因表达 ,α MHC基因表达相应减少 ,苦参碱对NE促心肌细胞直径增大及3 H Leu掺入率增加作用无明显影响 ,但显著抑制NE致心肌细胞MHC同工蛋白的病理性转换作用 ,即增加α MHC基因表达 ,减少 β MHC基因表达。 结论 :苦参碱对NE促心肌细胞肥大作用无明显影响 ,但显著逆转NE致MHC同工蛋白的病理性转换作用 ,故苦参碱在心肌细胞肥大的防治中仍有一定价值     

Relationship between lipids levels and right ventricular volume overload in congestive heart failure

BackgroundThe relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechan-isms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels.MethodsWe collected data of clinical characteristics, echocardio-graph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels[including total cho-lesterol（TCL）, high-density lipoprotein cholesterol（HDL-C）, low-density lipoprotein cholesterol（LDL-C）, and triglycerides（TG）]and right ventricle end diastolic diameter （RVEDD）, left ventricle end diastolic diameter （LVEDD）, right atrium diameter （RA）, left atrium diameter （LA）, or left ventricle ejection fraction （LVEF） were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area.ResultsThere was a significantly inverse correlation between TCL le-vels and RVEDD （r=-0.34,P〈0.001） and RA （r=-0.36,P〈0.001）. Other lipids such as LDL-C, HDL-C, and TG had asimilar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use.ConclusionsLipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as wellas identify a causal relationship, if any.     

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

Myosin is a molecular motor, which interacts with actin to convert the energy from ATP hydrolysis into mechanical work. In cardiac myocytes, two myosin isoforms are expressed and their relative distribution changes in different developmental and pathophysiologic conditions of the heart. It has been realized for a long time that a shift in myosin isoforms plays a major role in regulating myocardial contractile activity. With the recent evidence implicating that alteration in myosin isoform ratio may be eventually beneficial for the treatment of a stressed heart, a new interest has developed to find out ways of controlling the myosin isoform shift. This article reviews the published data describing the role of myosin isoforms in the heart and highlighting the importance of various factors shown to influence myosin isofrom shift during physiology and disease states of the heart.     

氯沙坦对心肌梗死后左心室肌球蛋白重链基因影响

目的 观察血管紧张素Ⅱ受体阻断药氯沙坦对急性心肌梗死后左心室心肌肌球蛋白重链（myosin heavy chain,MHC）基因表达的影响.方法 Sprague-Dawley大鼠24只随机分为3组,正常对照组,急性心肌梗死组,氯沙坦急性心肌梗死组,每组8只.急性心肌梗死造模后第2日开始灌胃给药,口服氯沙坦日剂量3 mg/kg,6周后测量左心室重量、进行心肌肌球蛋白重链基因分析.结果 急性心肌梗死组大鼠心脏重量指数明显增加,氯沙坦治疗后心脏重量指数明显下降（P＜0.01）;Northern plot发现,急性心肌梗死组大鼠心肌细胞的α-MHC mRNA表达量明显下降,而β-MHC mRNA的表达量则显著上升;而氯沙坦治疗组大鼠心肌的α-MHC mRNA表达较急性心肌梗死组增加,α-MHC mRNA表达明显降低（P＜0.01）.结论 氯沙坦能减轻梗死心肌肥厚,改善梗死心肌心室重构,机制与其调节心肌MHC的基因表达有关.     

Alterations in both death and survival signals for apoptosis in heart failure due to volume overload

Heart failure is known to be associated with an increase in cardiomyocyte apoptosis; however, neither its occurrence nor the mechanisms involved in hearts failing due to volume overload are completely understood. This study examined some of the signal pathways, which are known to regulate pro- or anti-apoptotic proteins, in heart failure due to volume overload induced by arteriovenous (AV) shunt in male Sprague-Dawley rats. Animals were assessed for cardiac function at 16 weeks of the operation and the left ventricle was used for studying apoptosis and associated signal transduction mechanisms. Hemodynamic and echocardiographic data indicated the presence of severe heart failure in AV shunt rats. A marked elevation in the amount of tumor necrosis factor-alpha and increased occurrence of apoptosis were detected in the volume overloaded myocardium. Western blot analysis revealed a significant increase in BAX and caspases 3/9 proteins in the failing hearts whereas the levels of phosphorylated Akt and Bcl-2 proteins were decreased. These data suggest that there is a downregulation in the Akt-dependent survival signal involving anti-apoptotic protein, Bcl-2, whereas the signals for the pro-apoptotic protein, BAX, are upregulated and these alterations may play a role in cardiomyocyte apoptosis in heart failure due to volume overload.     

A comparative serial echocardiographic analysis of cardiac structure and function in rats subjected to pressure or volume overload

Heart failure is a leading cause of death that is reaching epidemic proportions. It is a clinical syndrome attributable to a multitude of factors that begins with a compensatory response known as hypertrophy, followed by a decompensatory response that eventually results in failure. Heart failure can be triggered when the heart is subjected to extended periods of pathological pressure overload (PO) or volume overload (VO). To date there have been no comparative serial echocardiographic studies outlining the progression of hypertrophy in PO versus VO rats. We hypothesized that PO or VO would induce differential cardiac remodeling leading to contractile dysfunction with subsequent heart failure. To address this hypothesis we used echocardiography to study the serial progression of heart structure and function in rat models of both PO- and VO-induced hypertrophy. PO or VO were induced by performing abdominal aortic banding or aortocaval shunt procedures, respectively, while cardiac structure and function were assessed in both models by M-mode and Doppler echocardiography at key time intervals. PO rats showed progressive wall thickening consistent with concentric hypertrophy, while VO rats showed marked left ventricular dilatation consistent with eccentric hypertrophy. Systolic dysfunction occurred early in VO compared to PO. Diastolic dysfunction was evident in PO, while VO showed signs of enhanced diastolic function. PO and VO induced differential changes in cardiac structure and function during the progression of compensated hypertrophy to decompensated heart failure.     

Modification of myosin gene expression by imidapril in failing heart due to myocardial infarction

The beneficial effects of imidapril, an angiotensin converting enzyme (ACE) inhibitor were investigated on changes in myofibrillar ATPase as well as myosin heavy chain (MHC) content and gene expression due to myocardial infarction (MI). Three weeks after occluding the left coronary artery, rats were treated with or without imidapril (1 mg/kg/day), for 4 weeks. The infarcted hearts exhibited depressed rates of left ventricular (LV) pressure development (57+/-2.4% reduction) and pressure decay (55.5+/-1.6% reduction). LV myofibrillar Ca(2+) ATPase activity, unlike that in the right ventricle (RV), was decreased in the infarcted animals compared with controls (6.8+/-0.4 vs 10.3+/-0.6 micromol Pi/mg/hr). MHC alpha-isoform contents were decreased by 47 and 41% whereas those of MHC beta-isoform were increased by 823 and 1200% in the LV and RV due to MI, respectively. MHC alpha-isoform mRNA levels were decreased by 55 and 35% whereas those for MHC beta-isoform were increased by 50 and 30% in the infarcted LV and RV, respectively. Imidapril treatment partially prevented the changes due to MI in LV function (rate of pressure development, 24+/-2.3% reduction and rate of pressure decay, 14+/-1.8% reduction), myofibrillar Ca(2+) ATPase activity (8.2+/-0.7 micromol Pi/mg/hr), MHC protein content (alpha-MHC, 24% reduction and beta-MHC, 525% increase) and MHC gene expression (alpha-MHC, 18% reduction and beta-MHC, 15% increase). The results suggest that the beneficial effects of ACE inhibition on the failing heart are associated with improvements in myofibrillar ATPase activities as well as prevention of changes in MHC isozyme protein contents and their gene expression.     

Myosin heavy chain synthesis during the progression of chronic tachycardia induced heart failure in rabbits

Chronic tachycardia causes LV dilatation and dysfunction, with no hypertrophy. However, the contributing mechanisms responsible for the left ventricular (LV) remodeling in the absence of myocardial growth in this model of heart failure remain unclear. Therefore, the goal of the present study was to serially examine changes in LV function, steady state myosin heavy chain (MHC) mRNA levels, in vivo synthesis rates, and abundance with the progression of chronic tachycardia induced heart failure. Adult rabbits (3.5–4.5 kg) were studied after one, two, or three weeks of pacing ventricular tachycardia (VT; 400 bpm) and in controls (n=6 for all groups). LV fractional shortening was reduced by 30 % at week one and by over 50 % at week three of chronic VT. End‐diastolic dimension (EDD) increased at week two compared to controls (1.66 ± 0.10 vs 1.35 ± 0.11 cm, p < 0.05) and increased further at week three of VT (1.70 ± 0.06 cm, p < 0.05). The progressive changes in LV geometry and function with chronic VT were not associated with concomitant time dependent changes in LV mass or MHC mRNA levels. In contrast, MHC fractional synthesis rates increased and reached statistical significance at week three of VT compared to controls (8.3 ± 0.8 vs 5.5 ± 0.5 %/day, p < 0.05). Despite the stable or increased MHC protein synthesis rates, there was no change in MHC protein abundance at any point during the progression of VT induced heart failure, implicating enhanced MHC protein degradation. Thus, this study demonstrated that a contributory mechanism for the LV remodeling and lack of myocardial growth, which occurs with VT induced heart failure, is enhanced contractile protein degradative processes. Received: 17 July 1997 , Returned for revision: 20 August 1997, Revision received: 8 September 1997, Accepted: 7 October 1997     

心力衰竭患者外周血淋巴细胞α/δ环磷酸腺苷反应元件结合蛋白基因表达水平

目的 探讨慢性心力衰竭(心衰)患者环磷酸腺苷反应元件结合蛋白(CREB)α或δ亚型基因表达及其他β受体信号转导相关基因表达水平的变化。方法 采用逆转录聚合酶链反应(RT-PCR)方法定量检测了正常人与心衰患者外周血淋巴细胞α环磷酸腺苷反应元件结合蛋白(α-CREB)、δ环磷酸腺苷反应元件结合蛋白(δ-CREB)、诱导性腺苷酸环化酶早期阻遏物(ICER)、β受体激酶1(β-ARK1)、β受体激酶2(B-ARK2)、β阻抑蛋白1(β—arrestinl)六种基因的信使核糖核酸(mRNA)水平。结果 核转录因子CREB的不同亚型出现不同变化,心衰时α—CREB表达水平升高(P<0.01),δ-CREB表达水平下降(P<0.05),CREB的调节蛋白ICER表达水平升高(P<0.01);受体脱偶联的关键调控蛋白β-ARK1、β-ARK2、β-arrestinl的基因表达水平在心衰患者中明显升高(P<0.01)。结论 β受体相关基因的异常表达可能是心衰β受体脱敏的重要的分子生物学机制。     

Left-right asymmetric ventricular expression of CARP in the piglet heart: regional response to experimental heart failure

BACKGROUND AND AIM: Cardiac ankyrin repeat protein (CARP), whose expression is down-regulated in response to doxorubicin (Dox) in vitro, has been proposed to be a marker of experimentally-induced cardiac hypertrophy in rodent models. In piglets, the rapid hypertrophy rate of the left ventricle (LV) as compared to that of the right ventricle (RV) represents a natural model of asymmetric ventricular enlargement. We tested whether CARP expression correlates with postnatal ventricular hypertrophy and to what extent CARP can be sensitive to Dox treatment in vivo. METHODS: CARP mRNA and protein levels were quantified (by Northern blot hybridization, semi-quantitative RT-PCR and Western blot) in the piglet heart, both during early postnatal development and upon Dox-induced cardiomyopathy (Dox-CM). RESULTS: The study revealed: (1) significantly augmented CARP mRNA and protein levels in the LV compared to the RV resulting in left vs. right asymmetry in ventricular CARP expression throughout early postnatal development; (2) dose- and chamber-dependent CARP mRNA and protein enrichment in ventricular myocardium in response to Dox; and (3) abolishment of asymmetric patterns of ventricular CARP expression at heart failure resulting from Dox-CM. CONCLUSIONS: (1) CARP is differentially regulated in the LV and RV during both postnatal development and disease; and (2) monitoring of ventricular CARP expression patterns can be used for further analysis of transition from compensated to overt heart failure.     

Caspase-3在慢性心力衰竭大鼠心肌重塑中动态表达及意义

目的探讨慢性心力衰竭大鼠心肌内半胱氨酸天冬氨酸蛋白酶3（caspase-3）表达及意义。方法40只雄性Wistar大鼠随机分为四组,假手术组、心力衰竭1d组、7d组、14d组各10只。以缩窄大鼠腹主动脉,造成左心室压力负荷,制备慢性心力衰竭大鼠模型。观察和比较成模后1d、7d、14d及假手术组左心室肌重量指数,Masson染色后对比心肌胶原含量,免疫组化法测定心肌中caspase-3蛋白表达水平。结果腹主动脉缩窄术后各组大鼠均发生左室重塑和纤维化,左心室肌重量指数、胶原含量及caspase-3蛋白表达均明显高于假手术组;caspase-3于正常心肌内表达较少,而在心力衰竭后心肌内表达则明显增多,且随着心力衰竭程度的加重而表达增多。结论caspase-3可能参与了大鼠压力负荷性心肌重塑的发生和发展,其水平的高低与慢性心力衰竭的严重程度密切相关。     

慢性心力衰竭患者血浆脑钠肽和内皮素-1水平与血流动力学的相关性

目的:探讨慢性心力衰竭(HF)患者血浆脑钠肽(BNP)、内皮素-1(ET-1)水平与血流动力学的相关性及其临床意义。方法:2004年3月~2005年5月住院慢性HF患者75例,行Swan-Ganz导管检查53例,用干式快速免疫荧光法定量和放射免疫法分别检测血浆BNP、ET-1水平,超声心动图检查左室舒张末期内径(LVEDD)。结果:随着NYHA心功能级别增加,肺毛细血管嵌压(PCWP)、平均肺动脉压(MPAP)、右房压(RAP)和血浆BNP、ET-1水平均显著升高(P<0.01)。血浆BNP、ET-1分别与PCWP、MPAP、RAP呈显著正相关(P<0.01)。多元线性回归提示ET-1水平为影响血浆BNP浓度的独立因素(标准化偏回归系数为0.28,P<0.01)。LVEDD≥60mm组(31例)血浆BNP和ET-1浓度分别为(968.23±478.63)、(129.45±88.56)ng·L-1,显著高于LVEDD<60mm组(44例)[(286.26±156.89)、(87.45±43.65)ng·L-1],P<0.01。结论:慢性HF患者BNP、ET-1水平与PCWP、MPAP、RAP显著正相关,BNP的释放直接与心室压力负荷过度和心室容积扩张相关,BNP是反映心室受损敏感指标,ET-1可刺激HF心室BNP的分泌。     

培哚普利对慢性心力衰竭患者血浆t-PA和PAI-1水平的影响

目的评价培哚普利对慢性心力衰竭(CHF)患者血浆组织型纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制物-1(PAI-1)水平的影响。方法采用酶联免疫吸附法测定60例CHF患者(CHF组)及20例健康人(正常对照组)血浆t-PA、PAI-1水平。CHF组患者又随机均分为常规治疗亚组和培哚普利亚组。培哚普利亚组在常规治疗基础上加用培哚普利2~4mg,每日1次。所有CHF患者治疗2周后复测血浆t-PA、PAI-1水平。结果CHF患者血浆t-PA、PAI-1水平比正常对照组明显增高(P<0.01)。治疗后,培哚普利亚组血浆PAI-1水平比常规治疗亚组明显降低(P<0.01),血浆t-PA水平比常规治疗亚组明显升高(P<0.01)。结论培哚普利不仅可降低PAI-1水平,而且可升高t-PA水平,改善内源性纤溶功能。     

慢性乙型肝炎患者外周血单个核细胞基质金属蛋白酶-1及其抑制因子基因的表达

目的 比较外周血单个核细胞(PBMC)及自身血清中基质金属蛋白酶-1(MMP-1)及金属蛋白酶组织抑制因子-1(TIMP-1)表达水平,探讨MMP-1及TIMP-1基因表达对肝纤维化的诊断价值.方法 实时荧光定量反转录聚合酶链反应(FQ-RT-PCR)方法分别检测37例慢性乙型肝炎患者及20例健康对照者PBMC中MMP-1及TIMP-1 mRNA的表达水平,双抗体央心酶联免疫吸附方法检测血清MMP-1及TIMI-1水平;慢性乙型肝炎患者均行肝组织穿刺活检,行纤维化程度分期(S).组间比较采用多个独立样本非参数检验,并作Spearman相关性分析.结果 健康对照组PBMC中MMP-1 mRNA及TIMP-1 mRNA呈低水平表达,慢性乙型肝炎患者PBMC中MMP-1mRNA表达水平与健康对照组比较差异无统计学意义,而TIMP-1 mRNA表达水平显著高于健康对照组的(0.48±0.80)lg拷贝/μL,血清TIMP-1也高于健康对照组的(158.29±58.58)μg/L.随着慢性乙型肝炎肝纤维化程度加重,各期之间MMP-1 mRNA的表达水平及血清MMP-1水平比较差异无统计学意义(χ~2=8.960,P=0.111;χ~2=7.898,P=0.211);从S1～S4,TIMP-1 mRNA表达水平依次为(1.67±0.84)、(3.48±2.08)、(5.86±3.47)及(8.14±6.48)lg拷贝/μL,血清TIMP-1水平依次为(233.73±64.84)、(262.10μ71.12)、(301.15μ62.74)及(381.15±152.75)μg/L,各期之间TIMP-1mRNA表达水平及血清TIMP-1水平比较差异均有统计学意义(χ~2=14.290,P=0.002;χ~2=12.209,P=0.007).PBMC中TIMI-1 mRNA、血清TIMP-1与肝纤维化呈正相关(r=0.752.P<0.01;r=0.530,P=0.008).结论 PBMC中TIMP-1 mRNA表达水平及血清TIMP-1水平与肝脏纤维化程度密切相关.PBMC中TIMP-1 mRNA及血清TIMP-1可以作为诊断肝纤维化的新指标,尤其PBMC中TIMP-1 mRNA诊断价值最大.     

慢性心力衰竭患者心脏β1受体自身抗体与心功能及QTcd的相关性分析

目的通过β1肾上腺素受体自身抗体水平的检测，分析其与心功能及心电图表现的相关性，并观察β受体阻滞剂卡维地洛的治疗作用。方法65例慢性心力衰竭患者采用酶联免疫法测定患者血清中β1受体自身抗体水平，据此分为β1受体自身抗体阳性组（β1阳性组）30例和β1受体自身抗体阴性组（β1阴性组）35例，采用超声心动图测量左室舒张末径，左室收缩末径和左室射血分数进行心功能检测，常规12导心电图测量QTcd值。在血管紧张素转换酶抑制剂、利尿剂和洋地黄制剂治疗基础上加用β受体阻滞剂卡维地洛，随访半年。结果（1）治疗前β1阳性组左室舒张末径显著大于β1阴性组[（66．01±5．47）vs（63．07±5．64）mm；P〈0．05）]，左室收缩末径大于β1阴性组[（54．24±8．43）vs（50．72±6．12）mm；P=0．052）]，左室射血分数显著低于β1阴性组[（32．16±9．00）vs（36．64±8．20）％；P〈0．05）]。治疗后两组左室舒张末径、收缩末径均较治疗前显著减小（P〈0．01），左室射血分数较治疗前提高（P〈0．01）。β1阳性组左室舒张末径、收缩末径和左室射血分数与β1阴性组无差异（P〉0．05）。（2）治疗前β1阳性组心率显著高于β1阴性组[（94±14）vs（87±16）次／min；P〈0．05）]，β1阳性组QTcd值显著大于β1阴性组[（71．14±34）vs（58．33±14）ms；P〈0．05）]，治疗后两组心率及血压均较治疗前显著减低（P〈0．01），β1阳性组QTcd值较治疗前显著减低（P〈0．05），β1阳性组心率和QTcd值与β1阴性组无显著差异（P〉0．05）。结论β1受体自身抗体阳性者心功能较差且QTcd值长，β受体阻滞剂可以抑制心肌重构，改善心功能，减小QT离散度，提示β1受体自身抗体参与心力衰竭的病理生理过程，阳性者可能临床预后差。     

心衰患者心肌中NHE1 mRNA的表达与血浆内皮素及心肌胶原的相关性研究

目的:观察心力衰竭(HF)患者心肌组织中钠氢交换体1（natrium-hydrogen exchanger 1,NHE1）的表达及其与血浆内皮素-1(ET-1)及心肌胶原的相关性,探讨NHE1、ET-1在HF、心肌纤维化发生发展中的作用。方法: 采用实时荧光定量PCR（FQ-PCR）检测35例HF患者心肌组织中NHE1 mRNA的表达水平。采用放射免疫分析法分别测定受试者血浆ET-1及Ⅰ型前胶原羧基端肽Ⅰ（PⅠCP）和Ⅲ型前胶原氨基端肽（PⅢNP）的含量。同时用心脏多普勒超声检查心脏左房内径、左室射血分数（LVEF％）。结果: FQ-PCR检测心功能Ⅰ、Ⅱ、Ⅲ级组HF患者心肌组织中NHE1 mRNA的△Ct值,分别为6.29±0.66、5.01±0.60和4.40±0.74。心功能Ⅱ级、Ⅲ级组患者心肌组织中NHE1 mRNA的表达明显高于心功能Ⅰ级组（P<0.01）,心功能Ⅲ级组患者心肌组织中NHE1 mRNA的表达明显高于心功能Ⅱ级组（P<0.05）。HF组ET-1及PⅠCP、PⅢNP的含量较对照组明显升高（P<0.01）,并随着HF程度的加重而增加,心功能Ⅱ级和Ⅲ级组显著高于心功能Ⅰ级组（P<0.05,P<0.01）,心功能Ⅲ级组显著高于心功能Ⅱ级组（P<0.05）;且ET-1及PⅠCP、PⅢNP的含量与NHE1 mRNA的△Ct值（r=-0.587,P<0.01）呈显著的负相关。ET-1与PⅠCP、PⅢNP含量（r=-0.418,P<0.05）呈显著的正相关。结论: HF患者NHE1 mRNA的表达与ET-1及PⅠCP、PⅢNP的含量均密切相关。NHE1在HF、心肌纤维化的发生和发展过程中可能起着重要作用。