Effects of thyroxine on cardiac function and lymphocyte β-adrenoceptors in patients with chronic congestive heart failure

Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-ARs) of patients with chronic congestive heart failure (CHF). Methods Twenty-eight patients with class Ⅲ or Ⅳ advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T50) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and 125I-pindolol radioligand binding was used to measure β-AR levels in peripheral lymphocytes. Results L-T50 therapy improved cardiac output ［CO, （2.98±0.31）L/min vs （3.24±0.28） L/min, P<0.01］, left ventricular ejection fraction (LVEF, 26.21%±3.21% vs 37.93%±9.01%, P<0.01), and decreased isovolumetric relaxation time (IVRT, 0.12±0.04 vs 0.10±0.02, P<0.01). Serum TH levels and the maximal number of β-AR binding sites (βmax ) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T50 administration induced a β-AR up-regulation on peripheral lymphocyte surfaces. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate. Conclusion TH administration improves cardiac function and β-AR expression in peripheral lymphocytes of patients with CHF.     

Clinical evaluation of valsartan and metoprolol tartrate in treatment of diabetic nephropathy with positive β1-adrenergic and anti-angiotensin II type 1 receptor antibody

Background  Studies have confirmed that angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitors (ACEI) in the treatment of diabetic nephropathy (DN) has special advantages. We observed the effects of valsartan and metoprolol tartrate hydrchloride in treatment of DN patients with positive β1-adrenergic and anti-angiotensin II type 1 (AT1) receptor antibody.

Methods  The epitopes of the second extracellular loop of β1 receptor (197-222) and AT1 receptor (165-191), were synthesized and used respectively to screen serum autoantibodies from patients with DN (n=371, group A), diabetes mellitus (DM) without renal failure (n=107, group B) and healthy blood donors (n=47, control, group C) by enzyme-linked immunosorbent assay (ELISA). Metoprolol tartrate 25–50 mg, three times per day, valsartan 160 mg, once a day, aspirin 100 mg, once a day, and nitrendipine 10–20 mg, three times per day, were given to DN patients with positive or negative autoantibodies. The cystatin C level and 24-hour urinary protein were measured before and after treatment.

Results  In DN patients, the positive rate of the autoantibodies against β1 receptors and AT1 receptor was 47.7% and 51.5%, respectively, which were significantly higher than those in DM patients and healthy controls (all P <0.01). Patients with anormalous cystatin C had higher positive rates of the autoantibodies than patients with normal cystatin C. Valsartan and metoprolol tartrate reduced proteinuria significantly (P <0.01) in DN patients with positive autoantibodies.

Conclusions  The findings suggest that these autoantibodies against β1 and AT1-receptor may play important roles in the pathogenesis of DN. Valsartan and metoprolol tartrate are effective and safe in the treatment of DN.

     

Effect of polymorphisms in the β2-adrenergic receptor on the susceptibility and pulmonary function of patients with chronic obstructive pulmonary disease: a meta analysis

Background  Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex disease of which the pathogenesis remains largely unknown. Many factors could influence COPD development and progression. One of them is the genetic risk factor. A severe hereditary deficiency of alpha-1 antitrypsin is the best genetic proof. Four single nucleotide polymorphisms (SNPs) of beta2-adrenergic receptor (β₂AR) result in single amino acid substitution. Two loci had been extensively studied and found that they could change the function of β₂AR. Two SNPs consist of substitutions of glycine for arginine at amino acid position 16, glutamic acid for glutamine at position 27. Many studies proved that polymorphisms at position 16 and 27 altered the lung function of COPD patients or the patient’s susceptibility to the development of COPD. However, there was no exclusive conclusion. Therefore, a meta analysis was done to investigate the effect of polymorphisms in the β2-adrenergic receptor (ADRB2) gene on the risk of COPD and lung function.

Methods  Comprehensive searches of MEDLINE, Embase, Ovid, HighWire, Cochrane Library, and Chinese databases (CBMdisc, VIP, CNKI, and Wanfang data) from January 1980 to September 2011 were performed, using the keywords: COPD OR chronic obstructive pulmonary disease AND adrenoreceptor OR adrenergic receptor AND polymorphism OR mutation OR variation. Case-control research or cross sectional studies in which diagnosis of COPD met the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines; all the studies reported the ADRB2 genotype at position 16 or 27. Outcomes measured were genotype frequency and forced expiratory volume in the first second (FEV₁%) in both the case and control.

Results  Twelve case-control studies and eight cross-sectional studies were included. Compared to the control (n=1225), neither Gly/Gly (n=527) nor Arg/Arg (n=422) homozygotes at position 16 demonstrated increased susceptibility to COPD, with odds ratios (ORs) of 0.95 (95% CI (0.68, 1.31), z=0.33, P=0.740) and 0.82 (95% CI (0.52, 1.28), z=0.88, P=0.381), respectively. Similar results were obtained for position 27, with ORs of 0.97 (95% CI (0.77, 1.23), z=0.21, P=0.833) for Glu/Glu homozygotes (n=357) and 0.82 (95% CI (0.53, 1.29), z=0.85, P=0.393) for Gln/Gln homozygotes (n=704) (control=1183). In patients with COPD, Arg/Arg homozygotes (n=41) had a similar FEV₁% compared with Gly/Gly homozygotes (n=102) (standardized mean difference (SMD)=0.88, 95% CI (–0.85, 2.62), z=1.00, P=0.319). The genotype distribution was different between Caucasian and Asian populations (all P <0.05 except the genotype Arg/Gly) for both position 16 and 27.

Conclusions  Polymorphisms of ADRB2 at positions 16 and 27 did not change the risk of COPD nor affect lung function or disease severity. The genotype distribution for these polymorphisms was different between Caucasian and Asian populations.

     

Association of angiotensin Ⅱ type 1 receptor gene polymorphism with essential hypertension

Objective To determine whether the polymorphism A1166C in the angiotensin Ⅱ type 1 receptor (AT1R) gene is associated with essential hypertension.Methods A case-control study was carried out using 125 hypertensive and 103 normotensive subjects. The A→C variant at position 1166 (A1166C) of t he AT1R gene was identified by polymerase chain reaction (PCR) and PCR/ restriction fragment length polymorphism (PCR/RFLP) analysis. The digestion products were separated on 2% agarose gels and visualized with ethid ium bromide under ultraviolet ray.Results The differences in C1166 allele frequency and in the AC genotype dist ribution of the AT1R gene between the hypertensive and normotensive groups were statistically significant (C allele: 0.092 vs 0.034, χ(2) =6.1 86, P&lt;0.05; AC genotype: 0.184 vs 0.068, χ(2) =6.654, P&lt;0.05).Conclusion The AC genotype is associated with essential hypertension, and the C a llele may be a marker for predisposition to hypertension in Chinese H an population.     

Expression and role of adrenomedullm and its receptor in patients with chronic obstructive pulmonary disease

Objective To investigate the expression and role of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary disease (COPD).Methods Small pulmonary artery remodeling was observed using morphometric analysis. The expression of ADM and ADMR mRNA in lung tissue was calculated by in situ hybridization in 9 COPD cases. Cardiac catheterization was performed in 22 COPD cases to monitor changes of hemodynamic parameters and patients were divided into two groups based on mean pulmonary artery pressure (mPAP). The cases without pulmonary hypertension (PH) were placed in Group A (n =12) and those with PH were placed in Group B (n =10). The levels of pulmonary arterial plasma ADM were measured by radioimmunoassay. Blood gas analysis was also conducted.Results The ratio of vascular wall thickness to external diameter (MT%) and the ratio of vascular wall area to total area (MA%) were higher in patients with COPD ( P < 0. 01). In situ hybridization showed that ADM mRNA and     

Autoantibodies against the myocardial β 1- adrenergic and M 2- muscarinic receptors in patients with congestive heart failure

Objective To determine whether autoantibodies against β 1- adrenergic and M 2- muscarinic receptors are related to patients with congestive heart failure (CHF). Methods Both synthetic peptides corresponding to amino acids sequence 197-222 and 169-173 of the second extracellular loops of the β 1 and M 2 receptors were used as antigens to screen sera from 265 patients.188 were congestive heart failure (CHF) patients with different heart diseases, among them 42 were ischemic cardiomyopathy (ICD) and 52 were idiopathic dilated cardiomyopathy (IDCM),44 were hypertensive heart disease (HHD),50 were rheumatic valvular heart disease (RVHD); 77 were controls, among them 36 were simple hypertension and 41 were healthy donors (NC). Results Positive sera for β 1- adrenergic receptor was found in 45. 73% (86/188) of CHF patients, while in the controls it was 10. 4% (8/77) (P&lt;0. 01); positive sera for M 2- muscarinic receptor in CHF patients was found in 49. 5% (99/188), while in the control it was 11. 7% (9/77) (P&lt;0. 01).The positive ratio of autoantibodies against β 1- adrenergic and M 2- muscarinic receptors in CHF patients with cardiac function class Ⅱ- Ⅲ (NYHA) were significantly higher than cardiac function class Ⅳ.The average titer of autoantibodies against β 1- adrenergic and M 2- muscarinic receptors of the former was significantly higher than the latter; 56. 1% of patients with autoantibodies against β 1- adrenergic receptor had autoantibodies against M 2- muscarinic receptor.Conclusions Autoantibodies against β 1- adrenergic receptor and M 2- muscarinic receptor were found in sera from heart failure patients with different cardiac diseases.We propose that autoantibodies against β 1 and M 2 receptors are not only related to the IDCM, but also to cardiac structural and functional changes.     

Effects of Bisoprolol on the ventricular function and hemodynamics in patients with atrial fibrillation and chronic heart failure

Background: Recent data suggest that beta-blockers can be beneficial in patients with chronic heart failure (CHF). Atrial fibrillation (AF) is present in a significant number of patients with CHF and is associateing with significant morbidity and increasing mortality rates. Thus it is necessary to establish therapy to improve the poor prognosis in this high-risk population, but a specific benefit of beta-blockers to the subset with concomitant AF and CHF has been little demonstrated. Objective: To examine the effects of Bisoprolol (6 months treatment) on the ventricular function and hemodynamics in patients with AF and CHF. Methods: 84 patients with stable CHF (NYHA≤Ⅲ class) and AF were assigned to Treated Group( n = 37) or Control group Ⅰ ( n = 22, 24-hour heart mean rate < 70/min) or Control Group Ⅱ ( n = 25, 24-hour heart mean rate ≥ 70/min) . All patients were given the basic therapy for CHF, and Treated Group received Bisopolol. Clinical and echocardiographic variables were measured in 3 groups     

Association between estrogen receptor β gene Rsa1 polymorphism and depressive disorder in peri-menopausal and menopausal women

Worldwide,theprevalenceofdepressionin womenissignificantlygreaterthaninmen. Availabledatasuggestthatestrogenisstrongly implicatedintheregulationofmoodandbehavior, aswellasinthepathobiologyofmooddisorders[1]. Someresearchers[2,3]administeredtransdermal estradiol0.05mg/dor0.1mg/dtoperi- menopausalwomenwithdepression.After3 weeksofestradioltreatment,mostwomen receivingestradiolexperiencedremissionof depression,comparedwithlesswomenreceiving placebo.ThemeanMont-gomery-Asberg DepressionRatingScal…     

美托洛尔对心力衰竭大鼠血流动力学及 Bcl－2、Bax 蛋白表达的影响

目的：探讨不同剂量美托洛尔（ Meto）对心力衰竭大鼠血流动力学及凋亡相关蛋白Bcl－2、Bax表达的影响。方法 SD大鼠100只随机分为5组（n＝20）：sham组不结扎腹主动脉,其余操作同HF组;HF组次全结扎腹主动脉;Meto小剂量组、Meto中剂量组、Meto大剂量组大鼠次全结扎腹主动脉术后第4周开始给Meto,剂量依次为1.25、5、20 mg／（ kg· d）,至第8周。术后第8周测定有创血流动力学指标后取材称量全心湿重（ HW）、全肺湿重（ LW）,计算心重指数（全心重量／体重,HW／BW）、肺重指数（肺重／体重比,LW／BW）,Western blot检测心肌抗凋亡基因Bcl－2与促凋亡基因Bax蛋白表达水平。结果 Meto各剂量组大鼠右心室收缩压（ LVSP）及左心室压变化速率最大值（±dp／dt max）较HF组升高（P＜0.01）,Meto各剂量组左心室舒张压（LVDP）、左室舒张末期压（LVEDP）及－dp／dt max较HF组降低（P＜0.01）,Meto大剂量组LVSP较Meto小剂量组、Meto中剂量组明显降低（P＜0.01）,Meto大剂量组＋dp／dt max较Meto中剂量组明显降低（P＝0.002）;而Meto大剂量组＋dp／dt max与Meto小剂量组比较, Meto大剂量组LVDP、LVEDP及－dp／dt max与Meto中剂量组比较差异均无统计学意义（P＞0.05）。 HW／BW随Meto治疗剂量的增加逐渐降低（P＜0.01）;Meto中剂量组LW／BW较Meto小剂量组降低（P＝0.003）,而Meto大剂量组LW／BW则较Meto中剂量组有所上升（P＝0.000）。 HF组大鼠心脏Bcl－2／Bax比值较sham组降低（P＜0.05）,而随着Meto治疗剂量的增加Meto各剂量组的Bcl－2／Bax比值较HF组逐渐增加。且小剂量组比值与sham组相当,中剂量组出现比值翻转。结论中剂量Meto治疗在HF大鼠中可在获得解剖病理和抗凋亡获益的同时,保证最大的血流动力学获益,而大剂量Meto治疗则可能限制心功能进一步改善。     

坎地沙坦联合美托洛尔治疗收缩性心力衰竭疗效观察

目的探讨坎地沙坦和美托洛尔联合治疗收缩性心力衰竭(SHF)的临床疗效。方法 120例SHF患者分为2组,每组60例。对照组患者给予利尿剂、扩血管药物及洋地黄等常规治疗;观察组患者在常规治疗的基础上,给予坎地沙坦和小剂量美托洛尔治疗;连续用药48周;观察2组患者的左心室射血分数(LVEF)、左心室舒张末期内径(LVEDD)及临床疗效。结果观察组总有效率显著高于对照组(P<0.05)。治疗前2组患者LVEF及LVEDD比较差异无统计学意义(P>0.05);与治疗前比较,治疗后2组患者LVEF增加(P<0.05),LVEDD减小(P<0.05);治疗后观察组患者LVEF高于对照组(P<0.05),LVEDD小于对照组(P<0.05)。结论坎地沙坦联合美托洛尔治疗SHF疗效确切,可以显著改善患者LVEF和LVEDD。     

培哚普利联合美托洛尔治疗慢性充血性心力衰竭疗效观察

目的 应用培哚普利联合美托洛尔对慢性充血性心力衰竭(CHF)患者治疗并进行临床观察,旨在评价二者联用临床疗效.方法 根据美国纽约心脏病协会心功能分级,将112例慢性心力衰竭患者随机分为两组.对照组56 例,采用常规治疗及培哚普利;实验组56例,在对照组治疗的基础上加用美托洛尔;两组用药后18个月,观察患者临床症状缓解率、左室舒张末期容积(LVDd)、左室射血分数(LVEF)和病死率.结果 两组治疗后临床症状缓解率相比,有显著性差异(P<0.01).两组治疗前后及治疗后组间左室舒张末期容积(LVDd)、左室射血分数(LVEF)改善有显著性差异(P<0.05),两组病死率有显著性差异(P<0.01).结论 培哚普利联合美托洛尔比单用培哚普利对慢性充血性心力衰竭的治疗更有效,可明显改善心功能,降低病死率,改善预后.     

美托洛尔治疗非瓣膜病慢性心力衰竭的耐受性观察

目的探讨β-受体阻滞剂(美托洛尔)在治疗慢性心力衰竭的剂量耐受性及临床疗效。方法对62例心衰患者在常规抗心衰治疗的基础上加用美托洛尔,并逐渐增加剂量至目标剂量,分别于服药前及达目标剂量后由专人监测心率、血压及左室射血分数(LVEF)等变化。结果美托洛尔的平均维持量为(132.27±44.20)mg/d,本组62例患者中达最大目标剂量者14例,18例因血压下降不能加量,21例因心率降低不能加量,9例因心功能下降而未达目标剂量。加用美托洛尔不同剂量后心功能都有不同程度改善,尤其以大剂量组改善显著(P<0.01)。结论不同患者对美托洛尔耐受性不同,加用美托洛尔治疗充血性心衰后所有患者心功能都有不同程度改善,尤以大剂量组改善显著(P<0.01)。     

β-受体阻滞剂治疗老年人心衰的临床观察

通过对３３例不同程度心衰的老年冠心病患者应用β－受体阻滞剂倍他乐克治疗的临床观察，结果表明：３３例患者经治疗后症状体征有明显好转。平均减慢心率２３次／ｍｉｎ，平均减少体重１４ｋｇ，平均动脉压治疗前后无明显变化。β－受体阻滞剂倍他乐克可使β１－受体数目增多，改善心肌收缩力，还可阻止、减轻儿茶酚胺对心脏的损伤，保护了心肌。倍他乐克通过减慢心率，增加心排出量。同时具有抑制肾上腺素能递质的作用，延迟房室传导时间及有效不应期，降低心肌耗氧量，认为选择适当的β－阻滞剂，对改善充血性心衰的症状和预后有确切的疗效     

美托洛尔对扩张型心肌病心力衰竭患者P波离散度的影响

目的:探讨美托洛尔对扩张型心肌病合并慢性心力衰竭(CHF)患者P波离散度的影响及其机制,分析其在心房颤动发生中的意义。方法:采用同步体表12导联心电图仪,观察40例心功能(NYHA分级)ⅡⅣ级CHF患者美托洛尔治疗前和治疗6个月后心电图的改变,计算P波最大时限和P波离散度;超声心动图测定左心房内径、左心室舒张末内径和左心室射血分数。分析P波最大时限和P波离散度与超声参数之间的相关关系。结果:32例CHF患者纳入统计分析。美托洛尔治疗6个月后P波最大时限较治疗前明显缩短((102.1±13.0)msvs(118.3±11.5)ms,t=9.568,P<0.05);P波离散度较治疗前显著降低((27.5±11.6)msvs(37.5±9.8)ms,t=7.723,P<0.05)。美托洛尔治疗前后P波最大时限和P波离散度均与左房内径呈显著正相关(治疗前r=0.411,0.475;治疗后r=0.624,0.486;P均<0.05)、与左室射血分数显著负相关(治疗前r=-0.418,-0.590;治疗后r=-0.554,-0.691;P均<0.05);而与心率、左室舒张末内径无明显相关性。结论:美托洛尔治疗扩张型心肌病合并CHF患者通过改善心功能使P波最大时限缩短,P波离散度减小,提示可能减少心房颤动的发生。     

螺内酯联合美托洛尔治疗舒张性心力衰竭疗效观察

目的探讨螺内酯联合琥珀酸美托洛尔缓释片治疗舒张性心力衰竭(DHF)的临床效果。方法 60例DHF患者分为观察组和对照组,每组30例。2组患者在常规治疗的基础上,对照组患者给予琥珀酸美托洛尔缓释片治疗,观察组患者给予螺内酯联合琥珀酸美托洛尔缓释片治疗,治疗12个月后观察2组患者心功能改善情况。结果与治疗前比较,治疗后2组患者心功能均显著改善,差异有统计学意义(P<0.05);治疗后观察组患者心功能改善显著优于对照组,差异有统计学意义(P<0.05)。治疗后2组患者左心室舒张末期内径(LVEDD)、A峰血流速度、左心房内径(LAD)显著低于治疗前(P<0.05),而E峰血流速度、E峰血流速度/A峰血流速度(E/A)、6 min步行距离(6MWD)显著高于治疗前(P<0.05);2组患者治疗前后心脏射血分数比较差异均无统计学意义(P>0.05)。治疗后观察组患者LVEDD、A峰血流速度、LAD显著低于对照组(P<0.05),而E峰血流速度、E/A、6MWD显著高于对照组(P<0.05)。对照组治疗前后患者血清I型前胶原羧基端肽(PICP)、N-末端脑钠肽前体(NT-proBNP)和醛固酮(ALD)水平比较差异均无统计学意义(P>0.05);治疗后观察组患者血清PICP、NT-proBNP和ALD水平显著低于治疗前,差异有统计学意义(P<0.05);治疗后观察组患者血清PICP、NT-proBNP和ALD水平显著低于对照组,差异有统计学意义(P<0.05)。结论螺内酯联合琥珀酸美托洛尔缓释片治疗DHF可显著改善患者心脏的舒张功能。     

小剂量倍他乐克在慢性充血性心力衰竭中的应用观察

目的：观察小剂量倍他乐克在慢性充血性心力衰竭的临床疗效。方法．45例慢性充血性心力衰竭患者在口服地高辛0．125-0．25mg／d及使用利尿，扩血管药同时加服倍他乐克，开始剂量6．25mg／次，2次／d，1周后视情渐增至12．5mg／次，2—3次／d。结果：45例患者，病情好转，心功能有不同程度改善。临床疗效评定：显效11例，有效34例。结论：慢性充血性心力衰竭患者在常规治疗基础上加服应用小剂量倍他乐克，可使患者心衰症状和心功能得到改善，与使用倍他乐克治疗前比较，有显著性差异（P〈0．01）。     

美托洛尔治疗高龄老年慢性心力衰竭的总结报告

目的:探讨美托洛尔治疗慢性心力衰竭的疗效和安全性。方法:76例老年慢性心力衰竭患者,平均74.2±6.8岁,随机分为治疗组(37例)和对照组(39例)。对照组采用心力衰竭的标准治疗方案:治疗组在心力衰竭标准治疗方案基础上加用美托洛尔,治疗1年。结果:治疗组心功能改善、左室舒张末内径减小,左室射血分数明显增加,与对照组比较有差异有统计学意义(P<0.05)。结论:美托洛尔治疗高龄老年人慢性心力衰竭安全、有效。     

心力衰竭患者血浆内皮素的变化及倍他乐克的影响

为探讨充血性心力衰竭（ＣＨＦ）患者血浆内皮素－１（ＥＴ－１）的变化及倍他乐克（Ｂｅｔａｌｏｃ）对之影响，采用放射免疫法及高效液相色谱法测定４３例ＣＨＦ患者血浆ＥＴ－１和去甲肾上腺素（ＮＥ）水平。４３例中２４例用倍他乐克＋常规治疗，１９例用常规治疗，疗程１月。结果表明：ＣＨＦ患者治疗前血浆ＥＴ－１和ＮＥ均显著升高，且与ＣＨＦ程度呈正相关；治疗后降低。常规治疗对ＥＴ－１和ＮＥ均无影响