卡维地洛对正常青年男性P波间期离散度的影响

目的探讨健康男性青年服用B受体阻滞剂卡维地洛后不同血药浓度下静息心电图P波间期离散度（Pd）与用药前比较有无显著性变化,以对卡维地洛的抗心律失常作用机理提供依据。方法对20名健康男青年在服用卡维地洛20mg前及服药后0．5、1、2、3、4、6、8、10、24h分别测血药浓度,并做静息心电图,于十二导联心电图测量P波间期离散度。并将数据进行统计分析。结果Pd变化与血药浓度的变化没有明显相关性,且与用药前结果比较无显著性差异,P〉0．05。结论卡维地洛对正常健康男性的Pd可能无影响,从反面证实,它主要对有病理情况下的心脏病患者有抗心律失常作用。     

卡维地洛对正常青年男性Q-T间期离散度的影响

目的探讨健康男性青年服用β受体阻滞剂卡维地洛后不同血药浓度下静息心电图QT间期离散度（QTd）与用药前比较有无显著性变化,以对卡维地洛的抗心律失常作用机制提供依据。方法对20名健康男青年在服用卡维地洛20 mg前及服药后0.5、1、2、3、4、6、8、10、24 h分别测血药浓度,并做静息心电图,于十二导联心电图测量Q-T间期离散度。并将数据进行统计分析。结果随着血药浓度的升高,QTd有缩小趋势,但与用药前比较各P值无显著性差异。结论卡维地洛对正常健康男性的QTd可能无影响,从反面证实,它主要对有病理情况下的心脏病患者有抗心律失常作用。     

卡维地洛对正常青年男性血压的影响

目的探讨健康男性青年服用β受体阻滞剂卡维地洛后不同血药浓度下静息坐位血压与用药前比较有无显著性变化,以评价卡维地洛的降压特点,为临床用药提供试验依据。方法对20名健康男性青年在服用卡维地洛20mg前及服药后0.5、1、2、3、4、6、8、10、24h分别测血药浓度,并监测各时间点坐位静息血压,并将数据进行统计分析。结果血压变化与血药浓度的变化没有明显相关性,与用药前血压比较有显著性降低,即P〈0.01。结论卡维地洛对正常健康男性降压迅速,并可长时间维持降压作用。无明显副反应,受试者耐受性良好。     

连续口服不同剂量胺碘酮对健康受试者心率及心律的影响

目的:观察连续口服胺碘酮600~800 mg.d-1对健康受试者心率、心律的影响。方法:16名健康男性,每日600 mg或800 mg连续分次口服胺碘酮。服药至出现各种缓慢心律失常时停药。试验过程严密监测心电图(ECG)和24 h动态心电图(Holter)。结果:ECG:胺碘酮800 mg组服药1 d后白昼心率即有明显下降,停药3周恢复至药前水平;用药后ECG最早出现的改变为PR间期延长。Holter:服药3 d时胺碘酮800 mg.d-1组平均心率及24 h总心率数较用药前明显减低。停药1周两组平均心率及24 h总心率数与用药前比较差异无统计学意义。结论:胺碘酮致心律失常作用的最早表现为P-R间期延长,与剂量呈正相关,提示服用胺碘酮时应重视对PR间期的监测。     

对抗心律失常药物房颤患者的观察

20个世纪80年代以前,很多的抗心律失常药物被用来治疗室性心律失常,也就是从那个时候开始,心律失常药物也集中用在房颤患者身上。在辅助检查中,心电图对心律失常用药后药物疗效观察起重要作用。心电图对心室率变化,对临床症状以及长R-R间期频数能进行比较可靠的分析。抗心律失常药物的使用,还可以使临床症状减轻或者心室率明显减慢,同时发现长R-R间期、室上性失常等,可以很好地对疗效进行判断。结果表现,房颤对使用抗心律失常药物后,心电图检查对患者随访,观察,诊断有很大帮助。     

特发性心房颤动的心率变异性与P波离散度的相关性分析

目的探讨特发性心房颤动（简称房颤）的心率变异性与P波离散度的关系。方法在动态心电图上分析30例共74阵特发性房颤患者（房颤组）的心率变异性指标：①特发性房颤发作前、后5min的心率变异性指标：低频段功率（LF）、高频段功率（HF）、LF／HF值、每5分钟的NN间期的标准差（SDNN）；②24h心率变异性指标：全部NN间期的标准差（SDNN）、每5分钟平均NN间期的标准差（SDANN）、相邻NN间期差值的均方根（RMSSD）、相邻NN间期差值大于50ms的心搏数占总心搏数的百分比（PNN50）。测量、计算P波最大时间（Pmax）、P波离散度（Pd），与30例健康者（对照组）进行比较。结果①特发性房颤发作前SDNN、HF较发作后升高，LF／HF降低，LF无明显变化。@24h时域分析显示房颤组的SDNN、SDANN、RMSSD、PNN50高于对照组。③房颤组的Pmax、Pd明显大于对照组。④房颤组的SDNN、SDANN、RMSSD、PNN50与Pmax、Pd呈正相关。结论特发性房颤怠者迷走神经张力增高，特别在发作前迷走神经张力有明显增强，并且其Pmax、Pd显著增高，两者之间有一定的相关性，可能是特发性房颤的发病机制之一。     

QT间期离散度在预测抗心律失常药物致心律失常中的作用

目的 研究QT间期离散度在室性心律失常患者中预测抗心律失常药物致心律失常的作用。方法 对364例室性心律失常患者使用抗心律失常药物,测量治疗前后QTcd及动态心电图,并与120例健康人进行对照。结果 定性心律失常治疗前与对照组比较,QTcd有显著性差异(F<0.01)。治疗好转组QTcd明显降低,与对照组无明显差异(P>0.05),无效组QTcd无明显变化,致心律失常组QTcd反而升高。QTcd在服药后 3～4天开始变化,5～7天时变化幅度最大,12～14天变化幅度变小。不同药物致心律失常发生率不同,乙吗噻嗪致心律失常最高(11.2％),胺碘酮(6.2％),普罗帕酮(10.5％),三组间比较无明显差异(P>0.05)。乙吗噻嗪、胺碘酮、普罗帕酮用药两周后QTcd比较无明显差异(P>0.05)。结论 QTcd值的变化可能是预测抗心律失常药物致心律失常作用的灵敏而重要的指标之一。     

国产伊布利特注射液对健康受试者心电图QTc间期的影响

目的:评价健康中国人单次静注新型Ⅲ类抗心律失常药物伊布利特后的心电图QTc间期的变化.方法:40例健康青年男性(24.03±3.19岁)随机分6组,分别静注伊布利特0.005 mg·kg-1(n=4),0.01 mg·kg-1(n=10),0.02 mg·kg-1(n=6),0.5 mg(n=6),0.75 mg(n=6)和1.0 mg(n=8).以心电图QTc间期为药效指标.结果:药后各组受试者QTc间期均明显延长:0.005,0.01和0.02 mg·kg-1剂量组的QTc间期变化率最大值分别为(12.42±6.71)%,(45.73±27.52)%,(64.23±11.28)%;0.5,0.75和1.0 mg剂量组的QTc间期变化率最大值分别为(45.5±27.9)%,(48.1±22.1)%,(64.5±11.6)%.高剂量组QTc间期变化程度大于低剂量组(P＜0.05).药后PR间期、QRS间期、血压、心率、心电监测、实验室检查均在正常值范围内,变化无统计学意义.无严重不良反应发生.结论:静注国产伊布利特注射液有效延长QTc间期,耐受性好.     

P波离散度与心房颤动的关系

房性心律失常的体表心电图预测指标较少,近年来对P波离散(Pd)和P波最大时限(Pmax)的研究较多,认为它是预测房颤的体表心电图的一个指标。Pd是指同步记录的12导联心电图中,不同导联测定的Pmax与P波最短时限(Pmin)的差值。现对我院2000年共收住的阵发性房颤及持     

右室起搏对心室同步性及P波离散度的影响

目的比较右室心尖部或流出道起搏对心室同步性及P波离散度的影响。方法对60例因病态窦房结综合征(SSS)或房室传导阻滞(AVB)需行永久起搏器植入术(VVI或DDD)患者,根据起搏部位,选择右室心尖部(RVA)起搏组(n=32,男15,女17),右室流出道(RVOT)起搏组(n=28,男14,女14)。追踪术前、术后(18±7)个月两组心电图P波离散度(Pd)、最大P波时限(Pmax)、QRS波时限变化、左房容积指数(LAVI)、主动脉射血前间期(APEI)与肺动脉射血前间期(PPEI)差值来评价起搏对心室同步性及心房电活动影响程度。结果与术前相比,两组Pd、Pmax、QRS、LAVI均明显增加,但RVA组Pd、Pmax、LAVI及QRS时限增量变化较RVOT大,P0.05。与RVA组相比,RVOT组APEI-PPEI差值及LAVI较小,P0.01。结论 (1)与RVA相比,RVOT起搏心室间电激动与机械收缩更同步;(2)右室起搏可致心房的电生理紊乱,导致Pd、Pmax的增大;(3)与RVA相比,RVOT起搏对心房电活动影响小。     

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.     

The contractility enhancing effect of the calcium sensitiser levosimendan is not attenuated by carvedilol in healthy subjects

OBJECTIVE: It was assessed whether the contractility enhancing effect of the calcium sensitiser levosimendan is altered by carvedilol. METHODS: Twelve healthy subjects received 2 mg levosimendan i.v. both alone and in addition to a 7-9-day treatment with 25 mg carvedilol orally, twice daily, in a cross-over, placebo-controlled, double-blind, randomised study. Systolic time intervals, heart rate, and blood pressure were measured at baseline and up to 2 h after drug administration. RESULTS: When levosimendan was administered in addition to carvedilol, the shortening of electromechanical systole QS2i (indicating increased contractility) was similar to that found with levosimendan alone ( P=0.475). Also, the maximum heart rate change was similar, although a statistically significant difference in heart rate was detected due to minor differences at two time points during the 2-h follow-up ( P=0.018). There were no differences in diastolic blood pressure response ( P=0.962), but the systolic blood pressure response was attenuated by about 4 mmHg with the combination ( P=0.013). CONCLUSIONS: The contractility enhancing effect of levosimendan was not altered in healthy subjects who had received carvedilol for at least 1 week. Heart rate and diastolic blood pressure responses were not altered either, while the systolic blood pressure response was blunted.     

Steady-state pharmacokinetics of carvedilol and its enantiomers in patients with congestive heart failure

Carvedilol is a relatively new drug with beta- and alpha 1-receptor blocking activity and antioxidant effects recently approved for the treatment of congestive heart failure (CHF). An ascending, multiple-dose study was completed in 20 male patients with stable New York Heart Association (NYHA) Class III or IV CHF. The pharmacokinetics of carvedilol, S(-)-carvedilol, R(+)-carvedilol, and the active metabolites of carvedilol was assessed at steady state after twice-daily oral administration of carvedilol for 7 days at 6.25, 12.5, 25, and 50 mg doses. Carvedilol exhibited stereoselective pharmacokinetics in CHF patients with dose-proportional increases in steady-state plasma concentrations of carvedilol and its enantiomers. Mean AUC and Cmax values for carvedilol were up to twofold higher in patients with Class IV CHF as compared to those with Class III CHF. Steady-state plasma concentrations of the active metabolites also increased in a dose-proportional manner and were typically 10% or less of that observed for carvedilol. In general, carvedilol was adequately tolerated by adult male CHF patients at the dose levels (6.25-50 mg) evaluated in this study as adverse events were consistent with those frequently observed in patients with CHF.     

卡维地洛联合参松养心胶囊对高血压伴阵发性房颤患者P波离散度的影响

目的：探讨卡维地洛联合参松养心胶囊对高血压伴阵发性心房颤动（PAF）P波离散度（Pd）的影响。方法：83例PAF患者，随机分成4组：卡维地洛实验组21例；参松养心胶囊实验组20例；联合用药组21例；对照组21例。实验组给予药物干预，观察药物对Pd及PAF发生率的影响。结果：实验组3个月后PAF的发生率、Pd较对照组明显降低，但是卡维地洛实验组，参松养心胶囊实验组和联合用药组间的Pd无显著差异。结论：单用卡维地洛或参松养心胶囊可以通过降低Pd来减少高血压患者PAF的发作。但是联用这两种药物却不能取得更好的效果。     

Stability indicating ultraviolet spectroscopic method for the estimation of ezetimibe and carvedilol

In this study, new and rapid stability indicating ultraviolet spectroscopic methods were developed and validated for the estimation of ezetimibe and carvedilol in pure form and in their respective formulations. Since both the drugs are poorly water soluble, 20% v/v acetonitrile in triple distilled water was selected as the solvent system for both the drugs. This ensured adequate drug solubility and maximum assay sensitivity. The linearity range for ezetimibe and carvedilol at their respective wavelength of detection of 232 nm and 238 nm was obtained as 2-50 microg/ml and 2-20 microg/ml respectively. The linear regression equations obtained by least square regression method, were Y = 0.0443 x (X) + 0.0106 for ezetimibe and Y = 0.1080 x (X) + 0.034 for carvedilol, where Y is the absorbance and X is the concentration (in microg/ml) of pure drug solution. The detection and quantitation limit as per the error propagation theory were found to be 0.4 microg/ml and 1.3 microg/ml respectively for ezetimibe and 0.7 microg/ml and 2.1 microg/ml respectively for carvedilol. The methods were employed with high degree of precision and accuracy for the estimation of total drug content in two commercial tablet formulations of each of the two drugs. It was concluded that both the developed methods are accurate, sensitive, precise, and reproducible. They can be applied directly for the estimation of drug content in pharmaceutical formulations.     

Development and characterization of a carvedilol-loaded self-microemulsifying delivery system

The objective of the work was to develop, optimize, and evaluate a self-microemulsifying drug delivery system of the poorly water-soluble drug, carvedilol. Solubility of carvedilol was determined in various vehicles. Ternary and pseudo-ternary phase diagrams were constructed to indentify the efficient self-emulsification region using oils, surfactants, and co-surfactants in aqueous environment. Optimized formulations were assessed for drug content, spectroscopic clarity, emulsification time, contact angle, zeta potential, particle size, and dissolution studies. Zeta potential was measured in the absence and presence of oleylamine, a positive charge inducer. On the basis of similarity and dissimilarity of particle size distribution, formulations were characterized using PCA and AHCA, a multivariate statistical analysis. Decrease in t_50% and increase in DE attributed to small globule size and eventually higher surface area. The relevance of differences in t_50% and DE was evaluated statistically by two-way ANOVA. DRIFTS, DSC, and X-RD studies indicated no incompatibility between drug, oil, and surfactants. The results of this study indicate that the SMEDD formulations of carvedilol owing to nanosize have the potential to enhance its absorption, without interaction or incompatibility between the ingredients.     

Impact of pharmacotherapy on lymphocyte volumes and activity of the Na+/H+ exchanger in patients with congestive heart failure.

Previous studies in patients with congestive heart failure (CHF) have revealed abnormalities of cellular volume that might have an impact on the dysregulation of peripheral vascular resistance. Human mononuclear leukocytes (HML) represent a model for the study of cellular volume regulation. We investigated the impact of enalapril and carvedilol on HML volume and on the activity of the Na+/H+ exchanger in 26 patients with CHF and 20 volunteers. Over a period of 4 weeks, 18 patients received enalapril in addition to the previous therapy while 8 patients additionally received carvedilol. HML diameters and the activity of the Na+/H+ exchanger were measured by a Coulter Counter. Both patient groups showed abnormally increased initial volumes of HML compared to the volunteer group at baseline. Four weeks of therapy with enalapril in addition to therapy with diuretics and digoxin did not result in a statistically significant reduction of lymphocyte volume, whereas add-on therapy with carvedilol to therapy with ACE inhibitors, diuretics and digoxin reduced the volume significantly. Alterations could not be found in the activity of the Na+/H+ exchanger in either patient group compared to volunteers. Supplementary drug therapy with carvedilol in patients with CHF leads to a reduction of the increased lymphocytic volume, possibly reflecting the beneficial effect of beta-blockade.