高压负荷性心衰幼鼠病理生理及卡维地洛的干预

目的：探讨后负荷过高的幼鼠慢性心力衰竭（chronic heart failure，CHF）发生发展的病理生理及卡维地洛的干预。方法：腹主动脉缩窄术制备幼鼠CHF模型。术后4周随机分3组：假手术对照组、CHF组、卡维地洛组。直接灌胃给药，8周后行血流动力学、心肌病理分析、心肌细胞凋亡及其检测血清中脂质过氧化物（LPO）和超氧化物歧化酶（SOD）含量。结果：与假手术组比较，左、右心室相对重量（LVRW，RVRW）、收缩压（SBP）、舒张压（DBP）、左室收缩压（LVSP）、左室舒张末压（LVEDP）、凋亡指数（AI）、LPO均显著升高（P〈0．01—0．05）；左室内压最大收缩率（＋dp／dtmax）、左室内压最大舒张率（-dp／dtmax）、SOD均显著降低（P〈0．01）。与CHF组比较，卡维地洛组LVRW、RVRW、SBP、DBP、LVSP、LVEDP、AI、LPO显著下降，＋dp／dtmax、-dp／dtmax、SOD显著升高（P〈0．01）。结论：心室重构、心肌细胞凋亡及氧化应激参与幼鼠CHF发生、发展的病理生理过程，而卡维地洛能延缓、抑制这一过程。     

洛沙坦和卡维地洛对高血压大鼠心肌中细胞外信号调节激酶途径的影响

 目的探讨血管紧张素Ⅱ受体拮抗剂洛沙坦和β-受体阻滞剂卡维地洛对自发性高血压大鼠(SHR)心肌中细胞外信号调节激酶(ERK)和丝裂原活化蛋白激酶磷酸酶(MKP-1)的影响。方法将21只雄性SHR随机分为SHR对照组、卡维地洛组、洛沙坦组组药物干预,并设WKY为对照,分别用免疫沉淀法和RT-PCR法测定大鼠心肌组织中ERK活性和MKP-1mRNA的含量。结果①给药8周后,卡维地洛组和洛沙坦组SHR的血压均较SHR对照组明显下降(P<0.01),且心肌肥厚指数也降低(P<0.05),其中洛沙坦组心肌肥厚指数降低更明显(P<0.05);②给药后,卡维地洛组和洛沙坦组SHR心肌组织中ERK活性较SHR对照组下降(P<0.01),MKP-1mRNA的表达增加(P<0.05),两组无明显差异。结论卡维地洛和洛沙坦均可通过增加MKP-1表达,降低ERK活性型的活性ERK抑制MAPK信号途径,逆转增加MKP-1表达,从而明显减轻心肌肥厚程度。     

卡维地洛治疗轻、中度高血压病72例

目的 :观察国产卡维地洛治疗轻、中度高血压病的临床疗效和安全性并与美托洛尔做对照比较。方法 :14 4例轻、中度高血压病人随机分为卡维地洛组与美托洛尔组各 72例 ,分别用卡维地洛 10～ 2 0mg ,po ,bid与美托洛尔 2 5～ 5 0mg ,po ,bid ,共 6wk。结果 :卡维地洛组总有效率 81% ,显效率4 4% ;美托洛尔组总有效率 72 % ,显效率 36 % ;2组疗效比较差异无显著意义 (P >0 .0 5 )。 2组wk 6末心率与治疗前相比均有显著差异 (P <0 .0 5 )。卡维地洛组wk 6末动态血压监测的SBP和DBP的T/P值分别为 6 1.2 %和 5 0 .3%。wk 6末卡维地洛组尿微量蛋白降低明显 ,与治疗前相比有显著差异 ,与wk 6末美托洛尔组相比亦有非常显著差异(P <0 .0 1)。 2组不良反应的发生率分别为 19%及 18% ,均较轻微。结论 :国产卡维地洛治疗轻、中度高血压病有效、安全、并对肾脏有很好的保护作用     

卡维地洛对87例充血性心力衰竭病人血浆细胞因子的影响

目的 :探讨卡维地洛对充血性心力衰竭(CHF)病人血浆细胞因子的影响。方法 :将 87例CHF病人随机分为常规组和卡维地洛组 ,常规组给予常规抗心力衰竭治疗 ,卡维地洛组在常规基础上按双周剂量递增方案加用卡维地洛口服 ,目标剂量2 5mg ,bid ,治疗 6mo。测定血浆肿瘤坏死因子α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 10 (IL 10 )及心功能 ,以健康人作对照。结果 :CHF病人上述细胞因子均高于健康组 (P <0 .0 1) ,治疗 6mo后卡维地洛组TNF α和IL 6降低 ,治疗前后分别为(4 6±s 18)和 (31± 15 )ng·L- 1,(35± 13)和 (15± 9)ng·L- 1,IL 10升高 ,分别为 (15± 6 )和 (2 4± 7)ng·L- 1(P <0 .0 1) ,TNF α/IL 10降低 ,心功能改善(P <0 .0 1)。结论 :卡维地洛降低炎性细胞因子、增加抗炎性细胞因子水平的这种免疫调节作用可能是其对CHF有益作用的机制之一     

卡维地洛对心力衰竭患者胰岛素抵抗的影响

目的:评价卡维地洛对心力衰竭患者胰岛素抵抗的影响.方法:45例心力衰竭患者,随机分为治疗组22例和对照组23例,分别给予卡维地洛(39.5±4.2)mg或美托洛尔(64.5±7.2)mg.观察治疗前和治疗后8周,心功能、空腹血糖、空腹胰岛素、胰岛素敏感指数的变化.结果:2组治疗后左室舒张末期内径(LVEDd)均减小(P<0.05),左心室射血分数(LVEF)及心输出量(CO)、短轴缩短率(FS)均有提高(P<0.05,P<0.01),但舒张功能均无改善.对照组对空腹血糖、空腹胰岛素、胰岛素敏感指数无影响,治疗组能降低心力衰竭患者的空腹胰岛素,增加胰岛素敏感指数.结论:卡维地洛不仅能改善患者的心功能,而且能改善心力衰竭患者的胰岛素抵抗.     

卡维地洛抑制大鼠颈动脉损伤后MMP-2和IGF-1的表达

目的 观察卡维地洛(CAR)对大鼠颈动脉损伤血管组织基质金属蛋白酶2(MMP-2)、胰岛素样生长因子-1(1GF-1)表达的影响,探讨卡维地洛防治再狭窄的机制.方法 雄性Wistar大鼠90只,随机分为假手术组、损伤组和CAR组,后两组行颈动脉球囊损伤术.3组均于术后1d、3d、7d、14d、28 d处死大鼠.光镜下观察血管损伤后内膜增生情况,用免疫组化和RT-PCR法检测MMP-2和IGF-1在各组术后不同时间点的表达情况.结果 与损伤组比较,术后14 d CAR组内膜面积、内膜与中膜面积比值显著减少,管腔面积显著扩大(P＜0.05);与损伤组比较,CAR组术后3～14d MMP-2表达显著减少(P＜0.05),7 ～ 28 d IGF-1表达显著降低(P＜0.05).结论 卡维地洛能有效抑制大鼠颈动脉损伤后MMP-2和IGF-1的表达,抑制血管平滑肌细胞(VSMC)迁移、增殖,降低内膜增生,从而减轻再狭窄.     

Carvedilol therapy for patients with Eisenmenger syndrome

Background: Eisenmenger syndrome is characterized by the development of pulmonary arterial hypertension with resultant intracardiac right-to-left shunt and hypoxemia in patients with congenital heart defects. In clinical practice, we found that these patients might benefit from carvedilol therapy. Thus, we designed this prospective, open label, observational study to evaluate the efficacy of carvedilol for patients with Eisenmenger syndrome. Methods Twenty patients(17.5 ± 4.8 years) with Eisenmenger syndrome were treated with carvedilol for 6 weeks. The efficacy of carvedilol on 6-minute walking distance, World Health Organization(WHO) functional class, arterial oxygen saturation and right ventricle systolic pressure were assessed.Results At the end of observation, change from baseline in 6-minute walking distance increased 36.35 meters(95% confidence intervals [CI] 25.43 to 47.27 m, P 0.01). WHO functional class was also significantly improved(P 0.05). Change from baseline in right ventricular systolic pressure assessed by echo was reduced by 8.11 mm Hg(95% confidence intervals [CI],-10.78 to-5.44 mm Hg, P 0.05). However, arterial oxygen saturation remained unchanged(87.5 ± 3.02 % at baseline versus 87.80 ± 7.29 % at the end of observation). Conclusions Carvedilol can improve clinical function, symptoms as well as exercise capacity in patients with Eisenmenger syndrome. These findings need to be confirmed in further randomized clinical trials.     

卡维地洛对阿霉素心肌病兔氧化应激的影响

目的:研究卡维地洛对阿霉素心肌病兔氧化应激的影响,并探讨氧化应激与慢性心肌毒性之间的关系。方法:将40只日本长耳白兔随机分为对照组、阿霉素组、美托洛尔组和卡维地洛组,每组各10只。耳缘静脉注射阿霉素(每次1ml.kg-1,每周2次,共8周)建立阿霉素心肌病模型,对照组采用耳缘静脉注射0.9%氯化钠(每次1ml.kg-1,每周2次,共8周)。3周后,对照组和阿霉素组以0.9%氯化钠(5ml.kg-1.d-1)灌胃,美托洛尔组和卡维地洛组分别给予美托洛尔(5mg.kg-1.d-1)和卡维地洛(5mg.kg-1.d-1)灌胃。2个月后,超声心动图观察各组心脏结构变化,检测兔血清中丙二醛(MDA)、超氧化物岐化酶(SOD)和N末端前体脑钠肽(NT-proBNP)水平,并制备兔左室楔形心肌块的灌注模型,记录快频率程序刺激条件下室性心律失常的发生率。结果:与对照组比较,阿霉素组左室舒张末径(LVEDd)增大、左室射血分数(LVEF)降低(均P<0.05),血清SOD活性降低、NT-proBNP和MDA浓度升高,室性心律失常发生率增加(均P<0.05)。与阿霉素组比较,美托洛尔组无显著性变化,卡维地洛组LVEDd缩小、LVEF升高(均P<0.05),血清SOD活性增加、NT-proBNP和MDA浓度降低,室性心律失常发生率明显降低(均P<0.05)。结论:与美托洛尔比较,卡维地洛对阿霉素心肌病有保护作用,并能降低室性心律失常的发生,其机制与氧化自由基降低密切相关。     

Amelioration of cyclosporine-induced testicular toxicity by carvedilol and/or alpha-lipoic acid: Role of TGF-β1, the proinflammatory cytokines,Nrf2/HO-1 pathway and apoptosis

Cyclosporine is an immunosuppressive agent that is used to prevent organ rejection after organ transplantation. Due to the widespread use of this type of surgery, the effect of cyclosporine on reproduction and fertility should have a specific interest. Our aim was to assess the effect of carvedilol and/or alpha-lipoic acid on cyclosporine-induced testicular toxicity in rats. Sixty male Wistar rats were divided into six equal groups: Control; cyclosporine; cyclosporine + carvedilol; cyclosporine + alpha-lipoic acid; cyclosporine + carboxymethyl cellulose; and cyclosporine + carvedilol +alpha-lipoic acid. Food intake, testis weight, testicular functions, serum testosterone, luteinizing hormone and follicle-stimulating hormone were measured. Also, testicular tissue 3 β-hydroxysteroid dehydrogenase, 17 β- hydroxysteroid dehydrogenase, paroxonase-1, proinflammatory cytokines, transforming growth factor beta-1, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Heme oxygenase-1 (HO-1) content and sperm characteristics were determined. Parts of the testes were subjected to histopathological and electron microscopic examination. The carvedilol/alpha-lipoic acid combination restored the food intake, testicular weight and functions, sperm characteristics, hormonal profile and the antioxidant defences compared to the use of each of these drugs alone. Also, this combination significantly ameliorated inflammation (P < .05) and induced significant increase in tissue Nrf2/HO-1 content (P < .05) and significant improvement of the histopathological and electron microscopic picture (P < .05) compared to the use of each of these drugs alone. So, carvedilol/alpha-lipoic acid combination might represent a novel therapeutic strategy to ameliorate testicular damage induced by cyclosporine.