过氧化氢对乳鼠心肌细胞内游离钙浓度的影响及卡维地洛的拮抗作用

目的　研究过氧化氢 (H2 O2 )对心肌细胞[Ca2 + ]i的影响 ,以及卡维地洛对H2 O2 诱导钙超载的拮抗作用。方法　采用SD大鼠乳鼠进行心肌细胞培养。实验分为 4组 :正常对照组 ;H2 O2 组 :加入终浓度为 10 0 μmol/L的H2 O2 ;卡维地洛组 :加入终浓度为 1μmol/L的卡维地洛 ;H2 O2 +卡维地洛组 :同时加入卡维地洛 1μmol/L与H2 O2 10 0 μmol/L。以Fluo 3/AM荧光指示剂负载 ,应用激光共聚焦显微镜技术 ,分别于加入H2 O2 后即刻和 15min时检测 [Ca2 + ]i的变化。结果　对照组和卡维地洛组心肌细胞内荧光强度和荧光光密度值较低。一加入H2 O2 ,细胞内荧光光密度值便开始增加 ,15min后细胞内荧光强度和荧光光密度值较对照组显著增高 (P <0 0 5 )。而H2 O2 +卡维地洛组细胞内荧光光密度值显著低于H2 O2 组 (P <0 0 5 )。结论　H2 O2 可引起心肌细胞内钙超载 ,卡维地洛能显著减轻H2 O2 诱导的心肌细胞内Ca2 + 超载     

国产卡维地洛片剂的人体药动学及相对生物利用度

目的 :对国产卡维地洛的人体药动学及其制剂的人体相对生物利用度进行研究 ,为临床用药提供依据。方法 :选择健康志愿者单剂量服用卡维地洛制剂后 ,应用反相高效液相色谱荧光检测法测定血清药物浓度。结果 :卡维地洛在我国人体内的药代动力学过程符合二室开放模型 ,试验药品和对照药品的主要药代动力学参数 :Cmax(98 89±27 60)ng/ml、(70 06±27 29)ng/ml ,Tmax(0 4849±0 2635)h、(0 6037±0 1707)h ,CL(0 1621±0 08057) (mg·h)/(ng·ml)、(0 1796±0 09198) (mg·h)/(ng·ml) ,V/F(c)(0 2127±0 1260)mg/(ng·ml)、(0 2777±0 1860)mg/(ng·ml) ,T1/2β(2 011±1 709)h、(1 959±1 156)h ,AUC(233 1±97 12)ng/(ml·h)、(168 0±70 61)ng/(ml·h) ;平均人体相对生物利用度值 (111 3±15 18) %。结论 :试验结果可指导中国人的临床用药方案设计。     

卡维地洛固体分散体的制备及其体外溶出度的测定

目的 :制备卡维地洛固体分散体 ,提高其溶解度和溶速率。方法 :以聚乙烯吡咯烷酮 (PVP)、聚乙二醇 -6000(PEG -6000)为载体 ,以溶剂法和熔融法制备固体分散体 ,并进行体外溶出度研究。结果 :载体比例越大 ,药物溶出愈快 ;载体比例愈小 ,差异愈显著。载体为PVP所制固体分散体的体外溶出行为总体优于载体为PEG -6000的固体分散体。结论 :本试验所制卡维地洛固体分散体能加速体外溶出 ,提高生物利用度 ,可用于制备高效制剂     

卡维地洛、比索洛尔和多沙唑嗪降压疗效比较

目的：观察并比较卡维地洛（Car）、比索洛尔（Bis）和多沙唑嗪（Dox）治疗轻、中度原发性高血压的降压疗效和安全性。方法：选择48例原发性高血压患者,随机分成3组。Car组15例（Car25-50mg,po,qd）;Bis组16例（Bis5-10mg,po,qd）;Dox组17例（Dox4mg,po,qd）。3组疗程均为4wk。检测各组服药后的血压、心率、肝肾功能、血糖和血电解质等。结果：Car组的降压总有效率为80.0％,Bis组为81.25％,Dox组为70.59％,3组疗效无显著差别（P＞0.05）,Car与Dox对心率无影响,而Bis具有减慢心率作用。3种药物对肝肾功能、血糖和血电解质无明显影响。结论：Car、Bis和Dox疗效相似,均能有效降低轻、中度原发性高血压,且无明显不良反应。     

The effects of chronic carvedilol therapy on QT dispersion in patients with congestive heart failure.

BACKGROUND: Carvedilol therapy reduces mortality from sudden cardiac death and progressive pump failure in congestive heart failure (CHF). However, the effect(s) of carvedilol on ventricular repolarization characteristics is unclear. AIM: The aim of the study was to investigate the effects of chronic carvedilol therapy on ventricular repolarization characteristics as assessed by QT dispersion (QTd) in patients with CHF. METHOD: Nineteen patients (age 53+/-12 years; 16 male, three female) with CHF (eight ischemic, 11 non-ischemic dilated cardiomyopathy) were prospectively included in the study. Carvedilol was administered in addition to standard therapy for CHF at a dose of 3.125 mg bid and uptitrated biweekly to the maximum tolerated dose. From standard 12-lead electrocardiograms the maximum and minimum QT intervals (QTmax, QTmin), QTd, corrected QT intervals (QTcmax, QTcmin) and corrected QTd (QTcd) values were calculated at baseline, after the 2nd and the 16th month of carvedilol therapy. RESULTS: A significant reduction was noted in the QTd and QTcd values with carvedilol therapy after the 16th month (QTd: 81+/-22 ms vs. 40+/-4.3 ms P<0.001; QTcd: 91+/-25 ms vs. 51+/-7 ms P<0.001), but not after the 2nd month (P>0.05). The resting heart rate was also significantly reduced after a 16-month course of carvedilol therapy (78+/-13 bpm vs. 66+/-15 bpm, P<0.05). Carvedilol therapy did not alter QTmax and QTcmax intervals (P>0.05), however, QT min and QTcmin significantly increased with carvedilol at the 16th month (P<0.001 and P<0.01, respectively). CONCLUSION: Long-term carvedilol therapy was associated with a reduction in QTd, an effect that might contribute to the favorable effects of carvedilol in reducing sudden cardiac death in CHF.     

卡维地洛对充血性心力衰竭神经激素及心功能的影响

为了解卡维地洛对充血性心力衰竭患者神经激素及心功能的影响 ,将 35例充血性心力衰竭病人双盲随机分为卡维地洛组、安慰剂组 ,两组病人基础临床特征相似。于治疗前、后检测血浆中去甲肾上腺素 (NE)、血管紧张素Ⅱ (AngⅡ )浓度、血浆肾素活性 (PRA) ,左心室射血分数 (LVEF)及左心室腔径变化 ,15例健康人为正常对照组。结果显示 :心衰患者血浆中NE、AngⅡ、PRA均较正常对照组升高 (P <0 .0 1) ,卡维地洛组与安慰剂组相比血浆NE、PRA、AngⅡ水平下降 (P <0 .0 1) ,LVEF升高 (P <0 .0 1) ,左室舒张末径 (LVDd)、左室收缩末径(LVDs)均缩短 (P <0 .0 1)、左室收缩末容量 (ESV)减小 (P <0 .0 1)。提示卡维地洛能阻断神经激素对充血性心力衰竭的不良影响 ,改善患者左心功能 ,长期使用可使扩大的左心室腔径缩小。     

美托洛尔联合卡维地洛治疗扩张型心肌病疗效及安全性观察

目的探讨美托洛尔联合卡维地洛治疗扩张型心肌病患者的疗效及安全性观察。方法随机将心内科收治的96例扩张型心肌病患者分为美托洛尔组,卡维地洛组,联合用药组,各32例。常规治疗基础上,美托洛尔组给予美托洛尔治疗,卡维地洛组给予卡维地洛治疗,联合用药组给予两种药物联合治疗。疗程16周,评价三组患者治疗后的心功能分级,左室收缩末期内径（LVESd）、左室舒张末期内径（LVEDd）、左心室射血分数（LVEF）及不良反应。结果美托洛尔组总有效率68.75%,卡维地洛组81.25%,联用组93.75%,三组比较具有显著差异,有统计学意义（P＜0.05）。三组均可明显改善扩心病左室收缩末期内径（LVESd）、左室舒张末期内径（LVEDd）、左心室射血分数（LVEF）,但联用组优有单药使用,卡维地洛组优于美托洛尔组,差异有统计学意义（P＜0.05）。结论联用组治疗扩心病效果优于单药使用,卡维地洛组治疗效果优于美托洛尔组。     

卡维地洛对急性心肌梗死患者神经内分泌激素及心功能的影响

为评价卡维地洛对急性心肌梗死(AMI)患者神经内分泌激素水平及心功能的影响 ,将 5 2例AMI患者随机分为卡维地洛组、美托洛尔组和对照组 ,于治疗前和治疗后 6个月分别采血检测血浆肾素活性 (PRA)、血管紧张素Ⅱ(AngⅡ)浓度、血浆醛固酮 (Ald)浓度、血浆去甲肾上腺素 (NE)和肾上腺素 (E)浓度 ,并测定左心室射血分数 (LVEF)和左心室腔径变化。结果显示 ,卡维地洛组治疗后血浆PRA、NE、E水平以及美托洛尔组治疗后血浆PRA水平与对照组比较均显著下降 (P <0 0 1) ;卡维地洛组治疗后与治疗前比较LVEF增加(P <0 0 1) ,与对照组比较 ,左心室舒张末容量 (LVEDV)减小 ,LVEF增加 (P <0 0 5 )。提示卡维地洛可以抑制心肌梗死后神经内分泌激素的过度激活 ,从而减缓左心室重塑 ,改善心功能     

卡维地洛治疗轻中度原发性高血压的临床疗效观察

目的:观察卡维地洛治疗轻中度原发性高血压的疗效和安全性.方法:随机单盲平行对照试验,符合条件的54例轻中度原发性高血压患者随机分为2组:卡维地洛组29例,柳胺苄心定组25例.每日分别口服卡维地洛20 mg和柳胺苄心定100 mg,分二次给药.每周随访1次.2周后,如患者舒张压>90 mmHg,则剂量加倍,即卡维地洛40 mg、柳胺苄心定200 mg.疗程4周.结果:(1)治疗4周末,卡维地洛组降压总有效率79.3%,柳胺苄心定组降压总有效率84.0%,两组比较无统计学差异.(2)卡维地洛组治疗前后收缩压下降幅度为12.4%,舒张压下降幅度12.9%.柳胺苄心定组治疗前后收缩压下降幅度为11.8%,舒张压下降幅度11.0%.两组比较无统计学差异(P>0.05).(3)不良反应的发生率相似,卡维地洛组为10.1%,柳胺苄心定组为19.2%,常见的不良反应为头晕、皮疹、丙氨酸转氨酶轻度升高,均较轻.结论:卡维地洛20 mg/d～40 mg/d,治疗轻中度原发性高血压安全有效.     

Effects of carvedilol on common carotid arterial flow, peripheral hemodynamics, and hemorheologic variables in hypertension

The effects of a beta-blocker, carvedilol, on peripheral hemodynamics and hemorheologic parameters were evaluated in 11 geriatric patients with essential hypertension [3 men and 8 women aged 62–79 years (mean, 68.6 years)]. Carvedilol was given orally after breakfast at a dose of 10 or 20 mg daily for 8 weeks. Peripheral hemodynamics, the common carotid arterial flow, and hemorheologic parameters were determined twice prior to administration and after 4 and 8 weeks of carvedilol treatment. The common carotid arterial flow was determined using the pulsed Doppler method. Peripheral hemodynamics were assessed by venous occlusion plethysmography. The hemorheologic parameters assessed include erythrocyte aggregation, erythrocyte deformability, plasma viscosity, whole-blood hematocrit, and platelet function tests. Erythrocyte aggregation was measured using an Erythrocyte Aggregometer MA-1 (Myrenne, USA), taking a high shear rate of 600 s^\t-1 and a low shear rate of 3 s^\t-1 as the indices. Statistical comparisons of values before and after carvedilol administration were made using the paired Student'st-test. Systolic and diastolic blood pressure were decreased by carvedilol. The common carotid arterial flow was increased, and peripheral hemodynamics were improved by carvedilol. Erythrocyte aggregation (measured at both a high and a low shear rate) and plasma viscosity were decreased, erythrocyte deformability was increased, and levels of circulating platelet aggregates were also improved by carvedilol. This improvement of hemorheologic variables may contribute to prevention of the initiation and progression of thrombosis and atherosclerosis in geriatric patients with essential hypertension.