卡维地洛和美托洛尔对大鼠急性心肌梗死后胶原重构影响的对比研究

目的　对比研究非选择性 β受体阻滞剂卡维地洛及选择性 β1 受体阻滞剂美托洛尔对大鼠心肌梗死后胶原的影响 ,以了解卡维地洛改善心室重构及心功能的机制。方法　将梗死后 4 8h存活大鼠分为心肌梗死对照组、美托洛尔组 (15mg·kg- 1 ·d- 1 )、低剂量卡维地洛组 (1mg·kg- 1 ·d- 1 )和高剂量卡维地洛组 (10mg·kg- 1 ·d- 1 )。另设假手术组。给药 6周后 ,测量血流动力学参数及心功能。取血测量血浆内皮素及血管紧张素Ⅱ。测量心肌梗死区及非梗死区的总间质胶原容积分数 (ICVF)及Ⅰ、Ⅲ型胶原的ICVF。结果　美托洛尔及卡维地洛均可减低左心室舒张末压、增加左心室内压最大上升和下降速率 ,以高剂量卡维地洛组效果最好。与心肌梗死对照组比较 ,高剂量的卡维地洛可减轻心肌非梗死区尤其是右心室的ICVF及Ⅰ、Ⅲ型胶原的ICVF。低剂量卡维地洛及美托洛尔对间质胶原影响不明显。结论　卡维地洛可抑制非梗死区胶原增生 ,减少心肌纤维化 ,而美托洛尔无此作用。卡维地洛对心肌纤维化的抑制可能较美托洛尔能更好地改善心肌梗死后心室重构及心功能     

Effect of metoprolol in postinfarction patients with increased heart size

Mortality was analysed in relation to clinical and radiologicalsigns of left ventricular failure in a doubleblind randomizedcomparison of 154 post-myocardial infarction patients assignedto metoprolol (100 mg b.i.d.) and 147 patients assigned to placebotreatment. The maximal respiratory rate in the coronary careunit and the relative heart size measured by chest X-ray examinationprior to discharge from hospital were used for evaluation ofmyocardial function. In the placebo group mortality was higherin those with elevated maximal respiratory rate (11% vs. 27%,P<0.05) and in those with larger hearts (8% vs. 33%, P<0.001).No increase in mortality in patients with findings of left ventriculardysfunction was found in the metoprolol treated group. Thiswas not due to an excess mortality in patients with preservedleft ventricular function, but rather due to a reduction inmortality among patients with impaired left ventricular function.In patients with relative heart sizes > 460 ml m^–2( = median), mortality was higher in the placebo treated patientsas compared to metoprolol treated patients (33% vs 16%, P<0.05). During the three year follow-up, repeat chest X-ray examinationsshowed similar heart sizes in the two treatment groups. Furthermore,treatment with digitalis and diuretics were similar in the twotreatment groups although more patients in the metoprolol groupwere withdrawn due to uncontrolled left ventricular heart failure(7 vs 1, P<0.05). We conclude that elevated maximal respiratory rate in the coronarycare unit and heart enlargement on a pre-discharge chest X-ray,indicate a worsened prognosis. This excess mortality is reducedby metoprolol treatment during a three year follow-up.     

β受体阻滞剂对心力衰竭大鼠模型心肌纤维化的影响

目的 探讨不同β受体阻滞剂对心力衰竭大鼠模型心肌纤维化的影响.方法 取Sprague-Dawley雄性大鼠,采用结扎前降支方法建立慢性心力衰竭模型.将存活动物随机分组为心力衰竭组(n=9)、卡维地洛组(n=10)、美托洛尔组a=8),并建立假手术模型(n=10),观察各试验组动物的血液动力学变化,进行心肌纤维化的相关指标测定.结果 与心力衰竭组[(4.7±2.5)mm Hg,1 mm Hg=0.133 kPa]比较,美托洛尔组[(3.9±3.0)mm Hg]、卡维地洛组[(4.0±2.6)mm Hg]心肌梗死后左心室舒张末压水平显著低,美托洛尔、卡维地洛改善左心室±dp/dt(P＜0.05).心力衰竭组羟脯氨酸水平[(4.9±2.6)mg/g]明显高于假手术组[(2.5±1.0)mg/g]及卡维地洛组[(2.8±1.8)mg/g],P＜0.05.卡维地洛组羟脯氨酸水平明显低于美托洛尔组[(4.6±2.3)mg/g],P＜0.05.心力衰竭组心肌间质胶原容积百分数、血管周围胶原面积/冠状动脉腔横断面积(PCVA/VLCA)明显高于假手术组及卡维地洛组(P＜0.05).卡维地洛组PCVA/VLCA(3.9±1.2)明显低于美托洛尔组(5.1±1.7),P＜0.05.结论 卡维地洛组胶原含量低于美托洛尔组,提示卡维地洛较美托洛尔有更强的抑制心肌梗死后心肌纤维化的作用.     

Beta-blockade in heart failure: a comparison of carvedilol with metoprolol.

OBJECTIVES: This study was performed to compare the long-term clinical efficacy of treatment with metoprolol versus carvedilol in patients with chronic heart failure. BACKGROUND: Beta-adrenergic blockade is of proven value in chronic heart failure. Metoprolol, a selective beta-blocker, is widely used, but recent trials suggest carvedilol, a nonselective beta-blocker with alpha-1-receptor antagonist activity and antioxidant activities, is also effective. It is uncertain, however, if these additional properties of carvedilol provide further clinical benefit compared with metoprolol. METHODS: In this randomized double-blind control trial, 51 patients with chronic heart failure and mean left ventricular (LV) ejection fraction of 26% +/- 1.8% were randomly assigned treatment with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy after a four-week dose titration period for a total of 12 weeks. Response was assessed by a quality of life questionnaire, New York Heart Association class, exercise capacity (6-min walk test), radionucleotide ventriculography for LV ejection fraction, two-dimensional echocardiography measurement of LV dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate variability. RESULTS: Both carvedilol and metoprolol produced highly significant improvement in symptoms (p < 0.001), exercise capacity (p < 0.05) and LV ejection fraction (p < 0.001), and there were no significant differences between the two drugs. Carvedilol had a significantly greater effect on sitting and standing blood pressure, LV end-diastolic dimension and normalized the mitral E wave deceleration time. CONCLUSIONS: Both metoprolol and carvedilol were equally effective in improving symptoms, quality of life, exercise capacity and LV ejection fraction, although carvedilol lowers blood pressure more than metoprolol.     

Prospective crossover comparison of carvedilol and metoprolol in patients with chronic heart failure

OBJECTIVES: This study investigates the effects of a change of beta-adrenergic blocking agent treatment from metoprolol to carvedilol and vice versa in patients with heart failure (HF).BACKGROUND: Beta-blockers improve ventricular function and prolong survival in patients with HF. It has recently been suggested that carvedilol has more pronounced effects on left ventricular ejection fraction (LVEF) compared with metoprolol. It is uncertain whether a change from one beta-blocker to the other is safe and leads to any change of left ventricular function.METHODS: Forty-four patients with HF due to ischemic (n = 17) or idiopathic cardiomyopathy (n = 27) that had responded well to long-term treatment with either metoprolol (n = 20) or carvedilol (n = 24) were switched to an equivalent dose of the respective other beta-blocker. Before and six months after crossover of treatment, echocardiography, radionuclide ventriculography and dobutamine stress echocardiography were performed.RESULTS: Six months after crossover of beta-blocker treatment, LVEF had further improved with both carvedilol and metoprolol (carvedilol: 32 +/- 3% to 36 +/- 4%; metoprolol: 27 +/- 4% to 30 +/- 5%; both p < 0.05 vs. baseline), without interindividual differences. There were no changes in either New York Heart Association functional class or any other hemodynamic parameters at rest. Dobutamine stress echocardiography revealed a more pronounced increase of heart rate after dobutamine infusion in metoprolol- compared with carvedilol-treated patients. After dobutamine infusion, LVEF increased in the carvedilol- but not in the metoprolol-treated group.CONCLUSIONS: When switching treatment from one beta-blocker to the other, improvement of LVEF in patients with HF is maintained. Despite similar long-term effects on hemodynamics at rest, beta-adrenergic responsiveness is different in both treatments.     

美托洛尔与卡维地洛在慢性心力衰竭中耐受性的比较

目的 :探讨美托洛尔与卡维地洛在慢性心力衰竭中的耐受性。方法 :186例慢性心力衰竭患者随机分成美托洛尔组与卡维地洛组 ,在常规抗心力衰竭治疗基础上从小剂量开始逐渐加用美托洛尔与卡维地洛 ,直至目标剂量维持。结果 :美托洛尔组平均维持剂量为 (81.1± 33.5 )mg/d ,坚持维持量者 80例 (84 .2 % ) ,卡维地洛组平均维持剂量为 (34.9± 14 .6 )mg/d ,坚持维持量者 78例 (85 .7% ) ,卡维地洛组较美托洛尔组更易达最大靶剂量 (5 8.2 %∶2 .1% ,P <0 .0 1) ,且剂量调整时间短 [(31.6± 9.4 )d∶(4 6 .7± 17.2 )d ,P <0 .0 1]。美托洛尔组降低心率 (16 .2± 3.5 )次 /min ,卡维地洛组为 (13.8± 4 .1)次 /min(P <0 .0 1)。美托洛尔组降低收缩压 (12 .9± 3.7)mmHg(1mmHg =0 .133kPa) ,舒张压 (6 .7± 2 .6 )mmHg ,卡维地洛组分别为 (14 .4± 4 .1)mmHg和 (7.9± 2 .9)mmHg (P <0 .0 5 )。结论 :慢性心力衰竭患者对美托洛尔和卡维地洛都具有良好的耐受性 ,美托洛尔对心率的影响较大 ,而卡维地洛对血压的影响较大 ,卡维地洛比美托洛尔更易达到最大靶剂量 ,且剂量调整时间短     

卡维地洛与美托洛尔对扩张型心肌病疗效比较的Meta分析

目的比较卡维地洛和美托洛尔治疗扩张型心肌病的疗效。方法计算机检索Cochrane图书馆、MEDLINE、EMbase、中国知网、维普数据库、万方数据库和中国生物医学文献数据库,查找自1980年1月至2011年12月公开发表的比较卡维地洛和美托洛尔治疗扩张型心肌病随机对照试验,同时辅以手检纳入文献的参考文献。按纳入排除标准进行筛选、资料提取和质量评价后,使用RevMan5.1软件进行Meta分析。结果共纳入5项研究,347例患者。Meta分析结果显示：与美托洛尔相比,卡维地洛对左心室射血分数的改善有统计学差异（MD=3.93,95%CI：2.30～5.55,P〈0.01）;而对左心室舒张末内径（MD=-1.57,95%CI：-3.71～0.57,P=0.15）、血浆脑钠肽（MD=-69.86,95%CI：-192.33～52.62,P=0.26）、NYHA心功能标准疗效评价（MD=1.24,95%CI：0.21～7.25,P=0.81）等指标的影响均无统计学差异。结论在扩张型心肌病的治疗中,卡维地洛能更显著提高患者左心室射血分数,但其在改善心功能的其他方面,与美托洛尔无明显差异。由于纳入研究数目和质量有限,建议临床审慎参考。     

卡维地洛与美托洛尔对心肌梗塞后大鼠血流动力学的影响

目的:研究比较卡维地洛与美托洛尔对大鼠心肌梗塞后血流动力学的影响。方法:结扎大鼠左冠状动脉建立急性心肌梗塞模型,术后24 h存活的147只SD大鼠以简单随机法分为心肌梗塞对照组(MI组,n=43),美托洛尔(20mg/kg.d)治疗组(M组,n=42),卡维地洛(10 mg/kg.d)治疗组(C组,n=42),另设假手术组(S组,n=20);各组按观察时点48 h和4周,再分为:MI组48 h和MI组4周,M组48 h和M组4周,C组48 h和C组4周,S组48 h和S组4周。M组、C组于术后24h直接灌胃法给药,并于术后48h及4周对相应的观察组进行血流动力学测定。结果:(1)与S 48h组相比,MI 48h组的主动脉收缩压(SBP)、舒张压(DBP)和平均压(MAP)、左心室收缩压(LVSP)和左心室内压最大上升和下降速率(±dp/dt)均显著降低(P<0.05~<0.01);(2)与S 4周组比较,MI 4周组心率、LVSP和±dp/dt显著降低(P<0.05~<0.01),左室舒张末压(LVEDP)则显著升高(P<0.01),而主动脉SBP、DBP和MAP无显著变化;(3)与MI 48h组相比,C48h组的SBP、MAP、LVSP、±dp/dt和心率均显著降低(P<0.05~<0.01),LVEDP无显著变化,而M 48h组血流动力学指标均无显著差异;(4)与MI 4周组相比,C4周组SBP、DBP、MAP和LVEDP均显著降低(P<0.05),LVSP、±dp/dt等无显著变化;而M 4周组只有LVEDP和心率显著降低(P<0.01)。结论:大鼠心肌梗塞后,可以发生血流动力学异常改变和左室功能异常。较长时间(4周)卡维地洛应用能有效降低AMI后大鼠左室舒张末压,改善血流动力学和左室功能,美托洛尔亦有相似作用。     

Comparison of metoprolol with low, middle and high doses of carvedilol in prevention of postinfarction left ventricular remodeling in rats

The dose-related beneficial effects of carvedilol on survival in heart failure have been verified, however, the effects on left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) have not been defined. This experiment was designed to compare the effects of low, middle, and high doses of carvedilol (LD-car, MD-car, and HD-car) with metoprolol (Meto) in preventing postinfarction LVRM in rats. After the left coronary artery was ligated, 177 surviving female SD rats were randomized to: (1) AMI (n = 35), (2) LD-car (0.1 mg x kg(-1) x d(-1), n = 35), (3) MD-car (1 mg x kg(-1) x d(-1), n = 35), (4) HD-car (10 mg x kg(-1) x d(-1), n = 37) and (5) Meto (2 mg x kg(-1) x d(-1), n = 35) groups. A sham-operated group (n = 16) was also randomly selected. Gastric gavage therapy lasted for 4 weeks. After hemodynamic studies, the rat hearts were fixed and pathologically analyzed. After exclusion of rats which died or had an infarct size < 35% or > 55%, complete data were obtained in 69 rats, comprising AMI (n = 11), LD-car (n = 11), MD-car (n = 12), HD-car (n = 12), Meto (n = 11) and sham (n = 12) groups. There were no significant differences in MI size among the five AMI groups (44.5-46.3%, all P > 0.05). Compared with the sham group, left ventricular (LV) end-diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all significantly increased, while +/- dp/dt was significantly decreased in the AMI group (all P < 0.001). Compared with the AMI group, heart rate was significantly decreased in all except the LD-car treatment groups (P < 0.05-0.01); LVEDP, LVV, LVW, and STh in the four treatment groups were also significantly decreased (P < 0.05-0.001) except LVW and STh in the Meto group (both P > 0.05)(LVEDP: 14.5 +/- 4.6, 12.1 +/- 2.4, 7.7 +/- 1.9 and 13.0 +/- 6.7 mmHg vs 24.1 +/- 5.2 mmHg; LVV: 0.82 +/- 0.1, 0.79 +/- 0.1, 0.72 +/- 0.1 and 0.72 +/- 0.1 mL vs 0.92 +/- 0.1 mL; LVW: 666 +/- 57, 622 +/- 70, 589 +/- 57 and 699 +/- 78 mg vs 730 +/- 79 mg; STh: 1.14 +/- 0.12, 1.18 +/- 0.21, 1.19 +/- 0.15 and 1.35 +/- 0.20 mm vs 1.33 +/- 0.29 mm; P < 0.05-0.001); while +/- dp/dt was significantly increased in each therapy group (P < 0.05-0.001). There were dose-effect relations in LVEDP and LVV in the carvedilol groups. The results indicate that low, middle and high dose carvedilol has dose-related effects in the prevention of postinfarction LVRM with respect to volume expansion and segmental hypertrophy in rats, while metoprolol prevents only LV dilatation but not hypertrophy.     

卡维地洛和美托洛尔治疗急性心肌梗死伴心功能不全的对比研究

目的: 比较卡维地洛和美托洛尔治疗急性心肌梗死(AMI)伴心功能不全患者的疗效和安全性.方法:107例AMI伴左心室收缩功能减退患者以1∶1随机分为卡维地洛组(54例)和美托洛尔组(53例).测定治疗前后临床心功能分级、血压、心率、左心室功能及肾功能和血糖、血脂水平.结果:两组治疗后NYHA心功能分级均改善,左心室射血分数增高,收缩末期容量降低(P均《0.05).治疗后,血糖、肌酐变化值卡维地洛组与美托洛尔组比较有统计学差异(P《0.05),而总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)变化值卡维地洛组与美托洛尔组比较无显著性差异.结论:卡维地洛治疗AMI伴左心功能不全患者安全,疗效与美托洛尔相似,但前者对糖代谢和肾功能可能有益.     

卡维地洛与美多心安治疗稳定型心绞痛的临床疗效比较

目的 :比较卡维地洛与美多心安治疗稳定型心绞痛 （SA）的临床疗效。方法 :将 SA患者随机分为卡维地洛治疗组 （n=80 ）和美多心安治疗组 （n=76 ） ,观察用药 6周后治疗有效率以及心肌耗氧量 （RPP）和两组患者治疗期间的心血管危险事件发生率。结果 :1卡维地洛组临床治疗总有效率明显高于美多心安组 （92 % vs80 % ,P<0 .0 5 ）。2卡维地洛组 RPP明显减少 ,用药前后分别为 （14 91± 2 2 5 ） k Pa· min- 1和 （12 32± 2 11） k Pa· min- 1 （P<0 .0 5 ） ;美多心安组用药前后分别为 （15 0 0± 2 70 ） k Pa· min- 1和 （14 99± 115 ） k Pa· min- 1 ,无显著差异 （P>0 .0 5 ）。结论 :卡维地洛临床疗效明显优于美多心安     

Effect of carvedilol and metoprolol on the mode of death in patients with heart failure

BACKGROUND: In the COMET study, carvedilol improved survival compared to metoprolol tartrate in 3029 patients with NYHA II-IV heart failure and EF <35%, followed for an average of 58 months. AIMS: To evaluate whether the effect on overall mortality was specific for a particular mode of death. This may help to identify the mechanism of the observed difference. METHODS: Of the 1112 total deaths, 972 were adjudicated as cardiovascular, including 480 sudden, 365 circulatory failure (CF) and 51 stroke deaths. For each mode of death, the effect of pre-specified baseline variables was assessed, including sex, age, NYHA class, aetiology, heart rate, systolic blood pressure, EF, atrial fibrillation, previous myocardial infarction or hypertension, renal function, concomitant medication, and study treatment allocation. RESULTS: In multivariate Cox regression analyses, compared to metoprolol, carvedilol reduced cardiovascular (RR 0.80, CI 0.7-0.91, p=0.0009), sudden (RR 0.77, CI 0.64-0.93, p=0.0073) and stroke deaths (RR 0.37, CI 0.19-0.71, p=0.0027) with a non-significant trend for CF death (RR 0.83, CI 0.66-1.04, p=0.07). Treatment benefit with carvedilol did not differ between modes of death, except for a greater reduction in stroke death with carvedilol (competing risk analysis, p=0.0071 vs CF death). There were no interactions between treatment allocation and baseline characteristics. CONCLUSION: Mortality reduction with carvedilol compared to metoprolol appears relatively non-specific and could be consistent with a superior effect of carvedilol on cardiac function, arrhythmias or, in view of the greater reduction in stroke deaths, on vascular events.     

卡维地洛对急性心肌梗死大鼠血流动力学和心肌胶原含量的影响

目的研究卡维地洛(Carvedilol)对大鼠急性心肌梗死(AMI)后血流动力学的影响及其与心肌组织中胶原含量的关系。方法23只AMI术后存活的雄性SD大鼠随机分为AMI对照组(n=11)和卡维地洛治疗(Carvedilol)组(n=12),另设假手术组(n=11)。给药6周后测量室间隔超声背向散射参数(平均背向散射积分标化值IBS%,背向散射积分周期变化值CVIB)及血流动力学参数、心功能指标。结果(1)与假手术组相比,AMI组大鼠SBP、DBP、LVSP及±dp/dtmax及其校正值(±dp/dtmax/LVSP)均显著降低,LVEDP显著增高,高频超声检测显示IBS%显著升高,CVIB显著降低(均为P<0.05)。(2)与AMI组相比,Carvedilol治疗组大鼠SBP、DBP及LVSP均未进一步降低(P>0.05),LVEDP显著降低,±dp/dtmax及其校正值(±dp/dtmax/LVSP)显著升高,高频超声检测显示IBS%显著降低,CVIB显著升高(均P<0.05)。结论第3代β受体阻滞剂Carvedilol的干预有助于恢复AMI大鼠受损的左室功能,这可能与其抑制非梗死区心肌胶原过度沉积有关。     

Beta-blocker treatment of chronic heart failure: comparison of carvedilol and metoprolol

Beta blockers have been shown to prolong survival in chronic heart failure. It is currently a matter of debate whether any beta blocker is superior to the other in terms of improving symptoms, left ventricular function, or prognosis. A number of comparative studies have been performed with metoprolol, a beta1-selective second-generation beta blocker, and carvedilol, a nonselective and vasodilatative third-generation beta blocker. This review will focus on the different pharmacological profiles of carvedilol and metoprolol as well as on the clinical consequences derived from these differences. The results indicate that in some studies carvedilol is superior to metoprolol in improving left ventricular ejection fraction. However, because there is no conclusive evidence that carvedilol is superior to metoprolol in terms of prognosis, it is not justified to substitute metoprolol with carvedilol. Comparative data on mortality reduction are not available before termination of the Carvedilol or Metoprolol European Trial. Nevertheless, the different effects of both beta blockers on the beta-adrenergic system have an impact on tolerability and beta-adrenergic responsiveness and thus exercise tolerance in heart-failure patients.     

Effect of very early intervention with metoprolol on myocardial infarct size

All patients with a presumptive diagnosis of myocardial infarction, who were seen within six hours of the onset of symptoms and had no reason for exclusion, were considered for entry into a trial to compare the effects of metoprolol and placebo on creatine kinase MB isoenzyme release. The trial was randomised and double blind. The median time from onset of symptoms to receiving trial drug was just under two hours. Two hundred and four patients (of whom 120 had myocardial infarction) received metoprolol and 187 (of whom 105 had myocardial infarction) received placebo. Infarct size was estimated semiquantitatively using cumulative release of the cardiospecific isoenzyme, creatine kinase MB. Mean creatine kinase MB isoenzyme was less in patients who received metoprolol, but the reduction did not achieve statistical significance. Clinical problems related to early intravenous metoprolol were uncommon.     

Effect of cardiac rehabilitation on myocardial perfusion reserve in postinfarction patients

Cardiac rehabilitation is believed to increase myocardial perfusion reserve (MPR), but this has not been adequately studied because of poor delineation of infarcted myocardium in previous studies. The purpose of this study was to determine the effect of cardiac rehabilitation on MPR in the remote and infarcted myocardium with contrast-enhanced magnetic resonance imaging; 39 postinfarction patients were recruited for this study and randomly assigned to a training group (n = 20) or a nontraining group (n = 19). Those in the training group participated in a 3-month rehabilitation training program at an exercise intensity of 55% to 70% of peak oxygen uptake (VO2); those in the nontraining group continued their usual lifestyle. Nineteen age-, weight-, and height-matched subjects without cardiovascular risk factors were selected as healthy controls. After myocardial infarction, a reduction in perfusion reserve was seen not only in the infarcted myocardium, but also in the remote myocardium. In the training group, exercise capacity increased by 15% (p <0.01), to the same level as in healthy controls. The post-training MPR increased in both remote (30%, p <0.01) and infarcted myocardium (25%, p <0.05) and reached the same level as in healthy controls. The change in exercise capacity correlated with the change in MPR in the remote myocardium (r = 0.55, p <0.001 for peak VO2). In the nontraining group, exercise capacity and MPR were unchanged. In conclusion, cardiac rehabilitation improves perfusion reserve in both infarcted and remote myocardium, with a parallel increase in exercise capacity.     

Effect of carvedilol on attenuating the acute myocardial infarction-induced myocardial fibrosis in rats

Carvedilol,nonselective β-adrenoreceptor antagonist,was showed protective effects against acute myocardial infarction(AMI)-induced myocardial injury,however,the mechanisms underlying the antifibrosis effect of carvedilol has not been well known.The aim of the present study was to investigate the potential mechanism for the anti-fibrosis effect of carvedilol against AMI-induced myocardial fibrosis in rats.Methods Male SD rats were randomized into the sham group,LAD surgery-AMI model group,AMI plus low dose of carvedilol treatment group(1 mg /kg per day,CAR-L),AMI plus medium dose of carvedilol treatment group(5 mg /kg per day,CAR-M) and AMI plus high dose of carvedilol treatment group(10 mg /kg per day,CAR-H).The passage 3 neonatal SD rat cardiac fibroblasts were used for hypoxia /normoxia(2 h /4 h) treatment in the presence of carvedilol(0,1,2 and 4 μM).Results Cardiac remodeling and impaired heart function were observed after 14-week LAD surgery treatment,however,and the cardiac remodeling and decreased ejection fraction(EF%) and fractional shortening(FS%) were efficiently rescued in the CAR-M and CAR-H groups.The up-regulated expressions of Col1a1,Col3a1 and α-SMA at mRNA and protein levels were significantly reduced in the CAR-M and CAR-H groups.The in vitro study showed that Col1a1,Col3a1 and αSMA expressions at both mRNA and protein levels were down-regulated by carvedilol in rat cardiac fibroblasts in a dose-dependent manner.Smad3 inhibitors,SIS-3 and naringenin,could efficiently decrease Col1a1,Col3a1 and α-SMA expressions in rat cardiac fibroblasts.Smad3 was shown significantly inactivated in carvedilol-treated rat cardiac fibroblasts.Conclusion Carvedilol negatively regulates Smad3 signal pathway and inhibits extracellular matrix related Col1a1,Col3a1 and α-SMA expressions,contributing to the anti-fibrosis effect of carvedilol against AMI-induced myocardial fibrosis in rats.     

美托洛尔和卡维地洛对慢性心力衰竭的影响

目的比较选择性β1受体阻滞剂美托洛尔和非选择性β受体阻滞剂卡维地洛治疗对慢性心力衰竭(CHF)代谢底物、细胞因子及心脏功能的影响。方法选择CHF患者86例(CHF组)及健康体检者25例(正常对照组)。CHF组患者又随机分为美托洛尔组(43例)和卡维地洛组(43例)。记录两组CHF患者治疗前后心功能分级及不良事件次数及TNF-α、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)含量。所有入选者均测定血清游离脂肪酸(FFA)含量。结果美托洛尔组和卡维地洛组患者经过治疗后心功能明显改善(P<0.01),其中卡维地洛组更加明显(P<0.01)。美托洛尔组不良事件40次,卡维地洛组不良事件24次(P<0.01)。血浆TNF-α、IL-1β和IL-6较治疗前显著降低(P<0.05)。卡维地洛组较美托洛尔组TNFα和IL-1β降低更明显(P<0.01,P<0.05)。CHF组患者血清FFA含量同正常对照组比较明显升高(P<0.01)。治疗后卡维地洛组血清FFA较美托洛尔组降低更明显(P<0.01)。结论β受体阻滞剂可以改善CHF患者心功能,降低血浆细胞因子及FFA水平,非选择性的β受体阻滞剂卡维地洛优于选择性的β1受体阻滞剂美托洛尔。