美托洛尔联合硝酸甘油治疗老年高血压伴左心衰的临床分析

目的：观察美托洛尔联合硝酸甘油治疗老年高血压伴左心衰的临床疗效及其对血管内皮生长因子（VEGF）,高敏C反应蛋白（hs-CRP）和脑钠素（BNP）的影响。方法：选取2009年6月至2010年12月入住我院的高血压伴急性左心衰患者150例,将其随机分为观察组和对照组,每组各75例。对照组在强心,利尿的基础上予以硝酸甘油治疗;观察组在对照组的基础上予以美托洛尔治疗。观察两组的疗效,血压,心率,血氧饱和度,血浆VEGF,hs-CRP和BNP的表达。结果：观察组的总有效率为94.67%,而对照组的总有效率为80.00%,观察组的总有效率明显高于对照组（P〈0.05）。两组治疗后,收缩压,舒张压,心率,VEGF,hs-CRP和BNP均较治疗前明显降低（P〈0.01）,观察组的降低水平较对照组更为明显（P〈0.01）;而两组治疗后的血氧饱和度较治疗前明显提高,观察组的提高水平更为明显（P〈0.01）。结论：美托洛尔联合硝酸甘油治疗老年高血压伴左心衰疗效显著,其机理可能与降低血浆中的VEGF,hs-CRP和BNP水平有关。     

Direct enantioseparation of some β-adrenergic blocking agents using impregnated thin-layer chromatography

The resolution of (±)-atenolol, (±)-propranolol and (±)-metoprolol into their enantiomers was achieved by TLC on silica-gel plates impregnated with optically pure

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-lysine (0.5%) and

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-arginine (0.5%) as the chiral selectors. In all cases, different combinations of acetonitrile–methanol solvent systems were found to be successful in resolving these compounds. Spots were detected using iodine vapour. The detection limit for both (±)-atenolol and (±)-propranolol was 2.6 μg and for (±)-metoprolol, it was 0.26 μg.     

Baroreflex dysfunction in rats submitted to protein restriction

Earlier studies from the authors' laboratory showed that malnourishment induces alterations in the cardiovascular homeostasis increasing the basal mean arterial pressure and heart rate. In this study, the authors evaluated whether the sympathetic and parasympathetic efferent activities contribute to changes in the cardiovascular homeostasis through altered modulation of the arterial baroreflex of malnourished rats. After weaning, male Fischer rats were given 15% (Normal Protein--NP) or 6% (Low Protein--LP) protein diet for 35 d. The baroreflex gain and latency were evaluated before and after selective autonomic blockades in control and malnourished rats. It was observed that malnourishment affected the baroreflex gain in response to activation and deactivation of the arterial baroreflex. Moreover, malnourished rats showed increased baroreflex latency as compared to that of control rats. Regarding the autonomic efferent activity directed to the heart, the data showed increased sympathetic and decreased parasympathetic efferent activities in malnourished rats, and such alterations could be related to the observed changes in the arterial baroreflex gain as well as in the basal mean arterial pressure and heart rate.     

Optimization of bilayer floating tablet containing metoprolol tartrate as a model drug for gastric retention

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing metoprolol tartrate (MT) as a model drug by the optimization technique. A 2³ factorial design was employed in formulating the GFDDS with total polymer content-to-drug ratio (X₁), polymer-to-polymer ratio (X₂), and different viscosity grades of hydroxypropyl methyl cellulose (HPMC) (X₃) as independent variables. Four dependent variables were considered: percentage of MT release at 8 hours, T_50%, diffusion coefficient, and floating time. The main effect and interaction terms were quantitatively evaluated using a mathematical model. The results indicate that X₁ and X₂ significantly affected the floating time and release properties, but the effect of different viscosity grades of HPMC (K4M and K10M) was nonsignificant. Regression analysis and numerical optimization were performed to identify the best formulation. Fickian release transport was confirmed as the release mechanism from the optimized formulation. The predicted values agreed well with the experimental values, and the results demonstrate the feasibility of the model in the development of GFDDS.     

Enantioselective determination of metoprolol and major metabolites in human urine by capillary electrophoresis

The enantiomeric separation of metoprolol and its metabolites in human urine was undertaken using capillary electrophoresis (CE). Resolution of the enantiomers was achieved using carboxymethyl-β-cyclodextrin (CM-β-CD) as the chiral selector. A 100-mM acetate buffer (pH 4.0) containing 5% 2-propanol and 10 mM CM-β-CD resulted in the optimum separation of the metoprolol enantiomers and its acidic metabolite in human urine. Following a single metoprolol oral administration of 100 mg racemic metoprolol tartrate, stereoselective pharmacokinetic analysis showed that urinary acidic metabolite 3 of metoprolol accounted for 62.3% of the dose with an R/S ratio of 1.23 and urinary unchanged metoprolol 1 accounted for 6.3% of the dose with an R/S ratio of 0.72.     

氯沙坦早期联合美托洛尔治疗高龄重症心力衰竭的疗效

目的:研究氯沙坦早期联合美托洛尔治疗高龄重症心力衰竭的临床疗效。方法:选取2010年1月至2013年1月本院住院治疗的60例高龄重症心力衰竭患者,采用随机数字表法随机分为氯沙坦联合美托洛尔治疗组、氯沙坦治疗组和对照组,每组患者20例;所有患者均采取常规治疗,对照组加用口服强心剂和利尿剂,氯沙坦治疗组在常规治疗的基础上加用氯沙坦,氯沙坦联合美托洛尔治疗组在常规治疗的基础上加用氯沙坦和美托洛尔,在治疗前及治疗后0.5a、1.0a检测所有患者的心功能、左室射血分数(LVEF)和血液中的B型脑钠肽(BNP),并观察治疗后1.0a的临床疗效。结果:治疗前三组患者的心功能、左室射血分数(LVEF)以及B型脑钠肽(BNP)间均无统计学差异(P0.05);氯沙坦治疗组、氯沙坦联合美托洛尔治疗组治疗后0.5a和1.0a的心功能和BNP均低于对照组(P0.05),而治疗后0.5a和1.0a的LVEF均高于对照组(P0.05);氯沙坦联合美托洛尔治疗组治疗后0.5a的心功能、LVEF以及BNP与氯沙坦治疗组无统计学差异(P0.05),而氯沙坦联合美托洛尔治疗组治疗后1.0a的心功能、LVEF以及BNP与氯沙坦治疗组均存在着统计学差异(P0.05);三组治疗后1.0a死亡率间存在统计学差异(P0.05);每年住院次数和平均住院日最少的是氯沙坦联合美托洛尔治疗组,其次为氯沙坦组。结论:氯沙坦与美托洛尔早期联合治疗高龄重症心力衰竭的疗效优于氯沙坦单独治疗。     

Gender Dependency of Circadian Blood Pressure and Heart Rate Profiles in Spontaneously Hypertensive Rats: Effects of Beta‐Blockers

This study investigated (i) blood pressure (BP), heart rate (HR), and their relation to urinary NOx and eNOS protein expression in male and female spontaneously hypertensive rats (SHR), as well as (ii) gender‐dependent cardiovascular effects of nebivolol (NEB) in comparison to metoprolol (MET) in SHR. BP and HR were measured telemetrically after a single intraperitoneal application of NEB or MET at 07.00 and 19.00 h in male rats and at 19.00 h in proestrus female rats. The two β‐blockers varied in time of decreasing BP and HR and also in duration. In males, MET decreased BP and HR for few hours exclusively when applied at the onset of the activity phase (i.e., at 19.00 h), while after its application at 07.00 h, BP and HR were unchanged. In females, MET also caused a short‐lasting BP and HR reduction, with the effect being more pronounced than in males. In males, NEB at either dosing time decreased HR and BP to a greater extent than did MET. This effect was evident both during the activity and rest periods and persisted for at least five days. In females, NEB provoked a similar, but more pronounced, effect on BP and HR in comparison to males. These findings demonstrate that significant gender‐dependent differences in the circadian profile of BP and HR exist. BP and urinary NOx as well as eNOS expression are inversely correlated, and the cardiovascular effects of NEB and MET vary, depending on the time of application as well as gender.     

早期足量应用美托洛尔对急性心肌梗死疗效及安全性的研究

目的:研究早期足量应用美托洛尔对急性心肌梗死的疗效及安全性.方法:将40例AMI患者随机分为治疗组和对照组.治疗组静脉缓慢注射美托洛尔15mg后予关托洛尔150-200mg/d口服;对照组按常规剂量给予美托洛尔25-50mg/d口服.其它治疗相同,两组治疗4周.比较两组治疗后QTcd、心律失常发生的种类、心肌耗氧指数、梗死后心绞痛、梗死延展的发生率和心功能的变化.结果:治疗组QTcd、室性心律失常发生率、心肌耗氧指数、梗死后心绞痛和梗死延展的发生率均低于对照组(P<0.05).心功能两组无显著性差异.结论,AMI患者早期足量使用美托洛尔可以从多方面获益,安全性高.     

ENOS is not activated by nebivolol in human failing myocardium

Nebivolol is a highly selective beta(1)-adrenoceptor blocker with additional vasodilatory properties, which may be due to an endothelial-dependent beta(3)-adrenergic activation of the endothelial nitric oxide synthase (eNOS). beta(3)-adrenergic eNOS activation has been described in human myocardium and is increased in human heart failure. Therefore, this study investigated whether nebivolol may induce an eNOS activation in cardiac tissue. Immunohistochemical stainings were performed using specific antibodies against eNOS translocation and eNOS serine(1177) phosphorylation in rat isolated cardiomyocytes, human right atrial tissue (coronary bypass-operation), left ventricular non-failing (donor hearts) and failing myocardium after application of the beta-adrenoceptor blockers nebivolol, metoprolol and carvedilol, as well as after application of BRL 37344, a specific beta(3)-adrenoceptor agonist. BRL 37344 (10 microM) significantly increased eNOS activity in all investigated tissues (either via translocation or phosphorylation or both). None of the beta-blockers (each 10 microM), including nebivolol, increased either translocation or phosphorylation in any of the investigated tissues. In human failing myocardium, nebivolol (10 microM) decreased eNOS activity. In conclusion, nebivolol shows a tissue-specific eNOS activation. Nebivolol does not activate the endothelial eNOS in end-stage human heart failure and may thus reduce inhibitory effects of NO on myocardial contractility and on oxidative stress formation. This mode of action may be of advantage when treating heart failure patients.     

氨氯地平联合美托洛尔治疗原发性高血压的临床疗效观察

目的：观察氨氯地平联合美托洛尔治疗高血压的临床效果及安全性。方法：对2012年4月至2012年11月期间在我科住院治疗的102例患者随机分成两组,对照组接受氨氯地平治疗,治疗组在对照组的基础上使用美托洛尔治疗,分析比较两组的疗效。结果：治疗组和对照组的血压以及心率较治疗前明显降低,差异有统计学意义（P〈0．01）;治疗组治疗后的舒张压与对照组治疗后的舒张压相比,差异有统计学意思（P〈0．01）;治疗组的总有效率高于对照组（P〈0．05）;治疗组的副反应低于对照组（P〈0．05）。结论：氨氯地平联合美托洛尔治疗高血压效果显著,优于单纯应用氨氯地平。