卡维地洛、比索洛尔、哌唑嗪对SHR心肌成纤维细胞增殖作用的对比研究

目的 观察卡维地洛(carvedilol)、比索洛尔(bisoprolol)、哌唑嗪(prazosin)对培养的SHR和Wistar大鼠心肌成纤维细胞(CFs)增殖的影响。方法 采用胰酶消化法培养CFs，用^3H—TdR法、MTT比色法分别观察carvedilol、bisolol、prazosin干预下CFs的增殖情况。结果 SHR、Wistar大鼠CFs^3H-TdR掺入及OD值随carvedilol浓度的增加而减低，呈剂量和时间依赖性。10^-5mo1／L carvedilol分别干预SHR和Wistar大鼠CFs72h其h其^H-TdR掺入分别减低52．1％和47．5％，OD值分别减低41．5％和35．3％，bisolol(10^-8mo1／L一10^-5mol／L)和przosin(10^-8mol／L一10^-5mol／L)则无此作用。结论 Carvedilol抑制心肌成纤维细胞增殖，并呈浓度及时间依赖性，高血压时，CFs对Carvedilol更为敏感。而Bisoprolol和Prazosin则对CFs细胞增殖无影响。     

Carvedilol promotes neurological function,reduces bone loss and attenuates cell damage after acute spinal cord injury in rats

Acute spinal cord injury (SCI) leads to permanent functional deficits via mechanical injury and secondary mechanisms, but the therapeutic strategy for SCI is limited. Carvedilol has been shown to possess multiple biological and pharmacological properties. The of the present study was to investigate the possible protective effect of carvedilol in SCI rats. An acute SCI rat model was established and neurological function was tested. After carvedilol (10 mg/kg, oral gavage) treatment for 21 days, the status of osteoporosis, neuron damage, astrocyte activation, inflammation, oxidative stress and apoptosis were evaluated in rats. Carvedilol significantly improved locomotor activity that was decreased by SCI. In addition, carvedilol promoted bone growth by regulating the expression of nuclear factor‐κB ligand (receptor activator of nuclear factor‐κB ligand; RANKL) and osteoprotegerin (OPG), inactivating osteoclasts and thereby increasing bone mineral density in tibias. In addition, carvedilol reduced SCI‐induced neural damage, increased neuron number and reduced astrocyte activation in the spinal cord. Furthermore, the production and mRNA expression of tumour necrosis factor‐α, interleukin (IL)‐1β and IL‐6 were significantly reduced, reduced glutathione content and superoxide dismutase activity were markedly increased and malondialdehyde content was markedly decreased in the spinal cords of carvedilol‐treated rats. These results indicate that carvedilol exhibits anti‐inflammatory and anti‐oxidative effects in SCI rats. In addition, the expression of Fas and Fas ligand was reduced by carvedilol treatment, which, in turn, reduced cleaved caspase 3 expression and finally decreased the number of apoptotic cells in the spinal cord. In conclusion, carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute SCI in rats.     

不同β-受体阻滞剂治疗心室收缩不同步特发性扩张型心肌病的临床疗效

目的：观察不同β-受体阻滞剂治疗心室收缩不同步特发性扩张型心肌病（IDC）的临床疗效。方法收集2009年1月至2011年6月,该院收治的65例 IDC 患者,分为卡维地洛组（n＝33例）和美托洛尔组（n＝32例）。分别于用药前和用药后6个月多普勒超声心动图检测患者心功能,ELISA 检测血浆中 N 末端原脑利钠肽（NT-pro-BNP）表达水平,并做长期随访。结果卡维地洛组较美托洛尔组左室收缩末内径降低和左室射血分数升高更明显,在改善心室收缩不同步状况和促进生存率方面卡维地洛组优于美托洛尔组。但是,两组血浆 NT-pro-BNP 在用药前后比较,差异无统计学意义（P ＞0．05）。结论卡维地洛可以有效改善心室收缩不同步 IDC 患者的心功能,提高患者生存率。     

卡维地洛对兔心肌梗死后转化生长因子β1表达和心室重构的影响

目的探讨卡维地洛对兔心肌梗死后转化生长因子β1（TGF-β1）的表达和心室重构的影响。方法采用结扎冠状动脉左室支建立心肌梗死（MI）模型（假手术组开胸后在相应部位挂线不结扎）。术后24h将存活兔分为3组：假手术组、MI组、MI＋卡维地洛组。各组饲养4周后行血流动力学检查;测量体质量,左、右心室重量;采用苦味酸-酸性品红（VG）染色检测非梗死区的胶原容积分数（CVF）;采用免疫组化检测TGF-β1的表达情况。结果MI组与假手术组比较,左心室重量/体质量值（RVW/BW）、右心室重量/体质量（LVW/BW）、左室舒张末压（LV-EDP）、非梗死区CVF均显著升高（P〈0.05或P〈0.01）,TGF-β1的表达显著增强（P〈0.01）;MI＋卡维地洛组与MI组比较,RVW/BW、LVEDP、CVF均显著降低（P〈0.05或P〈0.01）,TGF-β1表达明显减弱（P〈0.05）。结论TGF-β1可能与心肌梗死后心室重构有关;卡维地洛能缓解心肌梗死后非梗死区的重构,其机制可能与减低TGF-β1的表达有关。     

Low-dose carvedilol reduces transmural heterogeneity of ventricular repolarization in congestive heart failure

Aim： To study the effects of carvedilol on the transmural heterogeneity of ventricular repolarization in rabbits with congestive heart failure （CHF）. Methods： Rabbits were randomly divided into 3 groups： control, CHF and carvedilol treated CHF group. Monophasic action potential duration （MAPD） in the 3 myocardial layers was simultaneously recorded. Results： All the rabbits in the CHF group had signs of severe CHF. Compared with the control group, the mean blood pressure and cardiac output were significantly decreased, while peripheral resistance was significantly increased in the CHF group. This proved that the CHF model was successful created with adriamycin in this study. Compared to the control group, the ventricular fibrillation threshold （VFT） was remarkably decreased and all MAPD of the 3 myocardial layers were extended in rabbits with CHF. However, the extension of MAPD in the midmyocardium was more obvious. The transmural dispersion of repolarization （TDR） was significantly increased in CHF. Low-dose carvedilol （0.25 mg/kg, twice daily） had no effects on ventricular remodeling. Treatment with low-dose carvedilol significantly increased VFT. Although the MAPD of the 3 myocardial layers were further prolonged in the carvedilol treated CHF group, the prolongation of MAPD in the midmyocardium was shorter than those in the epicardium and endocardium. Treatment with low-dose carvedilol significantly decreased TDR in CHF. Conclusion： In the present study, the transmural heterogeneity of ventricular repolarization increased in the rabbits with CHF. Low-dose carvedilol decreased the transmural heterogeneity of ventricular repolarization in CHF, which may be related to its direct electrophysiological property rather than its effect on ventricular remodeling.     

卡维地洛与培哚普利联合干预心肌梗死后心力衰竭对心肌细胞凋亡和肌浆网Ca^2＋泵活性的影响

目的：探讨β受体阻滞剂卡维地洛与血管紧张素转换酶抑制剂培哚普利联合干预心肌梗死（MI）后慢性心力衰竭对心肌细胞凋亡和肌浆网（SR）Ca^2＋泵活性的影响及意义．方法：通过结扎大鼠左冠脉建立慢性心力衰竭模型,术后1wk开始分别给予卡维地洛[6mg／（kg·d）]、培哚普利[4ms／（kg·d）]、特拉唑嗪[2mg／（kg·d）]、卡维地洛[6mg／（kg·d）]及培哚普利[4mg／（kg·d）]联合干预9wk,对照观察血流动力学、左室心肌细胞凋亡、SR Ca^2＋泵活性的变化．结果：与假手术组（SH组）相比,心力衰竭组（HF组）左室舒张末压（LVEDP）显著升高（P〈0．01）,＋dp／dtmax,-dp／dtmax显著降低（P〈0．01）,心肌细胞凋亡指数增高,SR Ca^2＋泵活性显著降低（P〈0．01）．卡维地洛、培哚普利单独及联合干预均降低LVEDP（P〈0．01）,升高＋dp／dtmax,-dp／dtmax（P〈0,01）,使左室心肌细胞凋亡比例降低,并使左室心肌SR Ca^2＋泵活性增高（P〈0．01）,联合干预变化更明显（P〈0．01）．特拉唑嗪组（Ter组）对上述指标无明显影响．结论：卡维地洛和培哚普利长期联合干预MI后慢性心力衰竭,能够改善血流动力学,抑制心肌细胞凋亡,并改善心肌SR Ca^2＋泵活性,优于任何单一药物干预．     

卡维地洛治疗慢性心力衰竭的随机对照研究

目的评价卡维地洛治疗慢性心力衰竭的疗效。方法将2007年1月～2010年6月收治入院的符合慢性心力衰竭诊断标准的82例患者随机分为对照组40例及治疗组42例。两组均给予常规心力衰竭治疗。治疗组在常规治疗基础上加用卡维地洛起始剂量3.125mg,2次/d,直至目标剂量25mg,2次/d;对照组在常规治疗基础上治疗加用美托洛尔,起始剂量6.25mg,2次/d,每2周逐步递增至最大剂量50mg。共双盲治疗3个月。结果治疗组心功能NYHA改善总有效率（92.9%）优于对照组的（77.5%）（P〈0.05）。两组治疗后LVEDD、LVES均较治疗前显著减小,LVEF较治疗前提高（P〈0.05或P〈0.01）,但治疗组较对照组变化更明显（P〈0.05）。结论在常规治疗充血性心力衰竭基础上加用卡维地洛治疗慢性心力衰竭效果满意,并在减少LVEDd和提高LVEF方面优于同类β受体阻滞剂美托洛尔。     

beta-blocker use and diabetes symptom score: results from the GEMINI study

AIM: The Glycemic Effect in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial compared the metabolic effects of two beta-blockers in people with type 2 diabetes and hypertension treated with renin-angiotensin system (RAS) blockade and found differences in metabolic outcomes. In this paper, we report the results of a prespecified secondary analysis of GEMINI that sought to determine the effect of these two beta-blockers on commonly reported symptoms. METHODS: The Diabetes Symptom Checklist (DSC), a self-report questionnaire measuring the occurrence and perceived burden of diabetes-related symptoms, was completed by GEMINI participants at baseline and at the end of the study (maintenance month 5). The DSC assessed symptoms in eight domains: psychology (fatigue), psychology (cognitive), neuropathy (pain), neuropathy (sensory), cardiology, ophthalmology, hyperglycaemia and hypoglycaemia. RESULTS: Comparison of the mean change in self-reported diabetes-related symptoms indicated a significant treatment difference favouring carvedilol over metoprolol tartrate in overall symptom score (-0.08; 95% CI -0.15, -0.01; p = 0.02) and in the domains for hypoglycaemia symptoms (-0.12; 95% CI -0.23, -0.02; p = 0.02) and hyperglycaemia symptoms (-0.16; 95% CI -0.27, -0.05; p = 0.005). Carvedilol resulted in fewer perceived diabetes-related symptoms in patients with diabetes and hypertension. CONCLUSION: Carvedilol resulted in a lower perceived burden of diabetes-related symptoms in patients with type 2 diabetes and hypertension. The addition of a well-tolerated beta-blocker to RAS blockade may improve hypertension treatment and quality of life in patients with diabetes.