Oral magnesium reduces ventricular ectopy in digitalised patients with chronic atrial fibrillation

Summary We have examined the effects of magnesium replacement therapy upon post-exercise heart rate and incidence of ventricular premature beats (VPB) in digitalised patients with AF. In 11 such patients, all of whom had serum magnesium concentrations of less than 0.85 mmol/l, treatment with magnesium glycerophosphate was associated with a significant reduction in number of VPBs (982 v. 416 VPB/24 h). Five patients had a high prevalence of ventricular ectopy (>300 VPB/24 h) and these subjects showed particularly marked decreases in VPBs during magnesium treatment (1998 v. 690 VPB/24 h). Three patients had slightly increased QTc intervals but these did not change during magnesium replacement. No significant changes were seen in the mean post-exercise heart rate although 2 subjects did show falls of 25% of more during magnesium replacement.We conclude that treatment with magnesium glycerophosphate may be associated with a decreased prevalence of ventricular ectopy in some digitalised patients with chronic AF and mild-moderate hypomagnesaemia.     

Diltiazem, verapamil, and quinidine in patients with chronic atrial fibrillation

The comparative effects of diltiazem and verapamil in 30 patients with long-standing atrial fibrillation were evaluated in a prospective clinical trial. After a one- to two-day washout period during which drugs other than digoxin were withdrawn, patients were randomly assigned to diltiazem or verapamil treatment groups. All therapy was double blind. Both drugs were given in ascending doses as follows: days 1-6 (part I): diltiazem, 180 mg/d, or verapamil, 240 mg/d; days 7-12 (part II): diltiazem, 360 mg/d, or verapamil, 480 mg/d. Patients failing to convert to sinus rhythm after 12 days had dosage reduced to 180 mg/d of diltiazem or 240 mg/d of verapamil, and quinidine, 750 mg/d, was coadministered for another six days (part III). Medication compliance was verified by frequent measurement of serum drug concentrations. Three verapamil patients dropped out during part I due to adverse reactions (dyspnea, pulmonary congestion, skin rash, or hepatotoxicity). The higher dosage of either verapamil or diltiazem in part II was not well tolerated, and in eight patients part III had to be initiated early due to symptomatic bradycardia. Only one patient in the diltiazem group converted to sinus rhythm, whereas five converted with verapamil (two with verapamil alone, three when combined with quinidine). Thus, diltiazem and verapamil alone are unlikely to convert atrial fibrillation to sinus rhythm. The combination of verapamil and quinidine, however, is a potentially useful pharmacologic approach, having converted atrial fibrillation to sinus rhythm in nearly 50% of patients.     

Magnesium deficiency may be an important determinant of ventricular ectopy in digitalised patients with chronic atrial fibrillation.

Digitalised patients with chronic atrial fibrillation (AF) have a high prevalence of ventricular premature beats (VPB); magnesium deficiency may be a contributory factor. We have used a magnesium loading-test to examine the relationship between ventricular ectopy and magnesium status in 14 digitalised patients with chronic AF. Among seven patients with infrequent VPB (less than 250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four subjects retained no significant quantities of magnesium, indicating magnesium repletion. Among the remaining seven patients, mean magnesium retention was significantly higher (33.1%, P less than 0.02) and all patients retained 20% or more of the load given. There was an overall relationship between Mg retention and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be determinant of ventricular ectopy in digitalised patients with chronic AF.     

Clinical pharmacokinetics of verapamil in patients with atrial fibrillation

Summary The pharmacokinetic parameters and oral bioavailability of the antiarrhythmic drug verapamil were determined in six patients with atrial fibrillation. Plasma samples were taken following i.v. injection of verapamil 10 mg (Isoptin^® 2 ml), and oral verapamil 80 mg (Isoptin^® 2 tablets of 40 mg). Verapamil and its N-demethylated metabolite, norverapamil, were analyzed to 1 ng/ml plasma by gas chromatography-mass spectrometry using deuterated standards. Following intravenous injection, the disposition of verapamil followed a biexponential pattern with a fast distribution phase and a slower elimination phase (t_1/2=5.79 h), corresponding to a plasma clearance of 0.26 1/kg/h. After oral administration, only an elimination phase was evident, with the same elimination rate (t_1/2=5.53 h). The oral bioavailability was 10.5%±7.5%. The norverapamil formed after i.v. and oral administration of verapamil had plasma half-lives of 5.86 h and 6.77 h, respectively. The elimination of verapamil in patients with atrial fibrillation was decreased compared to that in healthy young volunteers and the oral bioavailability was lower. Very good correlation between the percentage reduction in heart rate and the log plasma concentration of verapamil was found in every patient during the elimination phase, irrespective of the route of administration. There was also a high correlation when the plasma concentration — effect data from all the patients were pooled (r=0.59,n=71;p<0.0005).     

慢性心衰患者发生房颤的多因素分析

目的通过回顾性分析慢性心衰患者的临床资料,对慢性心衰患者发生房颤的因素进行分析。方法选择2009年1月至2011年1月期间该院心脏科收治的慢性心力衰竭（NYHAII-IV）患者330例,根据患者是否发生心房颤动（AF）将其分为AF组与非AF组两组,并对两组患者的临床资料进行统计分析。结果 330慢性心力衰竭患者中共发生房颤85例（25.76%）为AF组,其余245例未发生房颤者则为非AF组。单因素COX回归分析表明患者重度心衰（III＋IV级别）、年龄、糖尿病、左室肥厚、左房直径、尿素氮、血肌酐、血尿酸、安体舒通为房颤发生的危险因素。而ACEI、洋地黄、血钠、血氯为房颤发生的保护因素。Logistic回归分析表明ACEI为心力衰竭患者初发AF的独立保护因素,重度心衰、左心室肥厚左心房直径则为AF发生的危险因素。结论重度心衰、左心室肥厚左心房直径则为AF发生的危险因素;ACEI为心力衰竭患者初发AF的独立保护因素,其能降低AF的发生。     

Twenty-four hour effects of oxprenolol oros and atenolol on heart rate,blood pressure,exercise tolerance and perceived exertion

Summary The effects of oxprenolol, a non-selective beta-blocker with moderate intrinsic sympathomimetic activity (ISA), given by the Oros delivery system, on resting and exercise heart rate and blood pressure have been compared over a 24-h period with those of atenolol, a beta₁-selective blocker without ISA. The effects on maximal and submaximal exercise tolerance and perceived exertion were studied in relation to the level of beta-blockade. 9 healthy subjects were treated with placebo, atenolol, 100 mg/day and oxprenolol Oros, 16/260 mg/day in random order, each for 5 days. Progressive maximal exercise tests and submaximal endurance tests at 80% of maximum aerobic exercise capacity were performed 2, 5 and 24 h after intake of the drugs.The reduction of blood pressure 2 and 5 h after drug intake was less pronounced after oxprenolol Oros than after atenolol, but by 24 h after the last dose the effects were similar. The peak level of beta-blockade (i.e. reduction in maximal exercise heart rate) was similar after oxprenolol Oros and atenolol. The minimal level of beta-blockade 24 h after the last dose was greater after oxprenolol Oros than after atenolol. Maximal exercise capacity and submaximal exercise tolerance were impaired after both beta-blockers. The subjective feeling of exertion did not differ between placebo, atenolol and oxprenolol Oros when related to the relative work load, except after the first minute of exercise, when the rating of perceived exertion was higher after atenolol.     

地尔硫治疗合并快速心房颤动的心力衰竭

目的 :观察地尔硫对合并快速心房颤动心力衰竭的疗效。方法 :4 2例合并快速心房颤动的心力衰竭病人分为地尔硫组 2 2例 ,硝酸甘油组2 0例 ,除常规治疗外 ,分别给予地尔硫 30mg或硝酸甘油 30mg ,均iv ,gtt,gd× 2wk。采用心功能分级和超声心动图检查左室射血分数 ,评价静脉滴注地尔硫和硝酸甘油的治疗效果。结果 :地尔硫对快速心房颤动心力衰竭治疗的有效率达 86% ,左室射血分数显著增加 ,且较硝酸甘油更明显。结论 :地尔硫对合并快速心房颤动心力衰竭治疗有效 ,不良反应少 ,较硝酸甘油疗效更好。     

调脂治疗对慢性心力衰竭患者左室舒张功能及运动耐量的影响

目的:应用他汀类调脂药物,通过观察其对慢性心力衰竭患者左室舒张功能、血浆N-端脑钠肽前体(Nt-proBNP)及运动耐量等指标的影响,探讨调脂药物对慢性心力衰竭患者的治疗作用。方法:将符合入选标准的慢性心衰患者随机分为2组,治疗组(标准治疗+调脂治疗)和对照组(标准治疗),均于治疗前后进行肝肾功能、血脂分析、血液流变学等常规检查。疗程6个月。对2组患者左室舒张功能、Nt-proBNP及运动耐量进行比较分析。结果:与治前比较,2组患者心功能分级均较治前明显改善,但组间比较差异无显著性;与治前比较,2组患者左室舒张功能(VE/VA)均改善(P<0.05),治疗组改善幅度优于对照组(P<0.05);与治前比较,2组患者Nt-proBNP浓度均降低(P<0.01),治疗组下降幅度优于对照组(P<0.01);与治前比较,2组患者运动耐量(6分钟步行距离测定)均有提高(P<0.05),治疗组略优于对照组,但差异无显著性;与治前比较,2组患者全血黏度、纤维蛋白原均有改善(P<0.05),治疗组略优于对照组,但差异无显著性。结论:在标准抗心衰治疗的基础上加用调脂药物,能进一步改善慢性心力衰竭患者的左室舒张功能,但对左室射血分数和运动耐量的改善与标准抗心衰治疗无差异。     

房间隔起搏对病窦综合征(快慢型) 患者房颤及心功能的影响

目的本研究拟选取房间隔作为新的心房起搏位置,与传统的基于右心耳的双腔起搏比较,观察该方式对病窦综合征（快慢型）患者房颤发作及心功能的影响。方法选取病窦综合征（快慢型）患者,实验组29例,对照组31例。术前心脏彩色超声测定左房内径,左室舒张末期内径,左室射血分数,测定血清N末端脑钠肽前体水平,均行双腔起搏器治疗。实验组先行心内电生理检查,选择双心房同步激动的房间隔最佳起搏点,心房电极置于该位置。对照组心房电极置于传统的右心耳。比较术后3月、6月、9月、12月时两组房颤负荷,左房内径,左室舒张末期内径,左室射血分数,血清N末端脑钠肽前体水平。结果置入起搏器术后1年,实验组无房颤发生和房颤负荷减少20例（71．4％）,与对照组比较差异有统计学意义（71．4％ VS 48．4％）,术后1年房颤平均每天发作时间,左房内径,左室舒张末期内径,左室射血分数,N末端脑钠肽前体均有显著性差异：（78．8±6．9）min VS （106．7±12．8）min,（36．2±4．8）mmVS（41．7-4-6．1）mm,（49．8±6．1）mm VS （66．5±4．2）mm,（63．3％±4．1％） VS （49．1％±6．9％）,（330．8±30．5）pg／ml VS （502．8±21．4）pg／ml。结论基于房间隔起搏的房室顺序起搏方式较传统的房室顺序起搏减少病窦综合征（快慢型）患者房颤的发作,改善左室重构,延缓心功能恶化。     

Effects of bepridil, diltiazem and verapamil on atrial refractoriness and heart rate in the conscious dog: comparison with quinidine

1. Bepridil at cumulative doses between 1.25 and 8.75 mg/kg and quinidine between 2.5 and 17.5 mg/kg given in conscious dogs with chronic atrioventricular block and implanted atrial pacing electrodes, dose-relatedly lengthened atrial effective refractory period (AERP), as reflected by the decrease in maximal atrial frequency determined by pacing. 2. Diltiazem shortened AERP at 0.25 mg/kg and lengthened it at 1.75 mg/kg, but both effects were very slight. 3. Verapamil between 0.06 and 0.435 mg/kg did not alter AERP at all. 4. Except for diltiazem at 0.75 and 1.75 mg/kg and bepridil at 8.75 mg/kg, each dose of each drug increased atrial rate. Each drug produced an increase in ventricular rate and a short-lasting lowering in mean blood pressure. 5. Thus, these results indicate that bepridil exhibits more marked antiarrhythmic potentialities than quinidine and that the atrial and ventricular tachycardic effects observed are mainly baroreceptor reflex effects.     

心房颤动合并心功能不全患者血清同型半胱氨酸水平的变化及临床意义

目的探讨心房颤动合并心功能不全的患者血清同型半胱氨酸(Hcy)水平变化及临床意义。方法选择113例持续性心房颤动患者作为试验组,同时选择114例窦性心律患者作为对照组,比较2组患者血清Hcy水平,并根据患者心功能情况分成不同的亚组,比较不同亚组间Hcy水平。结果与对照组比较,房颤组Hcy水平明显升高,差异具有统计学意义(P<0.05);2组中,Hcy水平均随着心功能分级升高而上升,差异有统计学意义(P<0.05),而相同心功能亚组中,Hcy水平明显高于对照组,差异有统计学意义(P<0.01)。结论 Hcy水平的升高促进心房颤动的发生,且与心房颤动患者心功能分级的严重程度相关。     

Effects of verapamil and atenolol on exercise tolerance in 5,000 m cross-country running: a double-blind cross-over study in normal humans.

The effects on exercise tolerance of 7-day treatment with a calcium channel blocker, verapamil 160 mg twice daily (b.i.d.), and a beta 1-selective blocker, atenolol 50 mg b.i.d., were compared in 10 healthy and physically active young subjects in 5,000-m cross-country running at high intensity. The study was a double-blind cross-over trial. Comparison was made with a single-blind placebo as well. Performance time was measured every 1,000 m in seven 5,000-m runs, in which subjects were instructed to keep to a constant fatigue perception (Borg scale rating). Both drugs significantly (p = 0.001) increased the performance time over the first 1,000 m as compared with placebo. However, running time after 1,000, 2,000, and 3,000 m was prolonged significantly less (p less than 0.05) by verapamil than by atenolol. For the entire 5,000-m run, atenolol caused a significant increase (p = 0.001) in mean running time by 1 min 34 s (i.e., 7.5%; 95% confidence interval 48 s to 2 min 21 s) as compared with placebo, whereas verapamil caused no significant change (+46 s).     

冠心病慢性房颤患者血清8-OHdG水平的研究

目的:探讨氧化应激标志物8-羟基脱氧鸟苷(8-OHdG)在冠心病慢性房颤患者体内水平的变化。方法:选择冠心病慢性房颤患者30例、冠心病窦律患者30例及健康对照组30例,应用酶联免疫吸附试验(ELISA)方法检测试验对象血清8-O-HdG水平。结果:冠心病慢性房颤组与冠心病窦律组相比血清8-OHdG浓度升高(P<0.05),与健康对照组相比8-OHdG浓度更高(P<0.05)。结论:冠心病慢性房颤患者体内存在8-OHdG水平的变化,氧化应激可能参与了冠心病慢性房颤的发生及发展,8-OHdG对冠心病后合并房颤具有预测价值。     

缬沙坦和美托洛尔联合治疗慢性心功能不全患者阵发性心房颤动

目的探讨缬沙坦和美托洛尔对慢性心功能不全患者阵发性心房颤动的影响。方法将138例慢性心功能不全患者阵发性房颤随机分为：胺碘酮组（Ⅰ组）、胺碘酮＋缬沙坦组（Ⅱ组）、胺碘酮＋美托洛尔组（Ⅲ组）、胺碘酮＋缬沙坦＋美托洛尔组（Ⅳ组）,治疗随访2年,比较四组治疗前后左心房内径,窦性心律维持率。结果 （1）Ⅰ组和Ⅲ组左心房内径均大于Ⅱ组和Ⅳ（P〈0.05）,而Ⅰ组和Ⅲ、Ⅱ和Ⅳ组的比较差异无统计学意义。（2）Ⅰ、Ⅱ、Ⅲ、Ⅳ组的窦性心律维持率Ⅰ组低于Ⅱ、Ⅲ和Ⅳ组（P〈0.05）。结论缬沙坦和美托洛尔联合治疗能减少慢性心力衰竭患者阵发性心房颤动的复发,缬沙坦和美托洛尔联合治疗可显著减慢左房的扩大。     

Effects of azimilide on heart rate and ECG conduction intervals during sinus rhythm in patients with a history of atrial fibrillation

The purpose of this study was to assess the effect of azimilide, a Class III antiarrhythmic drug, on ECG conduction intervals recorded during sinus rhythm in patients with a history of symptomatic atrial fibrillation or atrial flutter. In Phase I clinical pharmacology studies, azimilide was associated with prolongation of the QT and QTc intervals on electrocardiograms recorded during sinus rhythm in normal subjects, but the effect of azimilide on the target population of patients with atrial fibrillation has not been reported in detail previously. Patients with a history of atrial fibrillation, atrial flutter, or both were randomly assigned to receive placebo or azimilide twice daily for 3 days and then qd thereafter. Azimilide doses of 50 mg, 100 mg, or 125 mg were tested. The RR, PR, QRS, QT, QTc(Bazett), and QTc(Fridericia) intervals were measured from electrocardiograms recorded at baseline and on Day 4 of test therapy. Increasing azimilide doses were associated with significant increases in the RR, QT, QTc(Bazett), and QTc(Fridericia) compared with changes in the placebo group based on the F-test for differences among treatment groups and the test for a dose response. In the azimilide 125 mg dose group, the mean change in RR was significantlygreater than the mean change in the placebo group (+61.4 ms in the azimilide 125 mg group vs. -14.1 ms in the placebo group). The mean change in QT was significantly greater in the azimilide 125 mg group than the mean change in the placebo group (+44.2 ms in the azimilide 125 mg group vs. -1.0 ms in the placebo group). The mean change in QTc using both correction methods was significantly greater in the azimilide 125 mggroup than the mean change in the respective placebo group: QTc(Bazett) +31.6 ms in the azimilide 125 mg group versus +2.1 ms in the placebo group and QTc(Fridericia) +35.8 in the azimilide 125 mg group versus +1.0 ms in the placebo group. It was concluded that in patients with a history of atrial fibrillation or flutter, azimilide was associated with statistically significant increases in RR, QT, QTc(Bazett), and QTc(Fridericia) when patients were in sinus rhythm.     

24-hour antiarrhythmic effect of conventional and slow-release verapamil in chronic atrial fibrillation

Summary Twenty-four-hour heart rate control by verapamil given as conventional tablets t.d.s., or as a new slow release formulation once daily, has been compared in an open cross-over trial. Eight patients with chronic atrial fibrillation and one with chronic atrial flutter were studied outside hospital.Trough serum concentration of verapamil did not differ during the two dosage regimens (59 ng/ml — conventional formulation and 49.3 ng/ml — slow release tablet). The average serum concentration of digoxin in the patients was not changed. Compared to the control phase, both dosage regimens significantly and equally reduced individual and average heart rates throughout the entire 24-h period. A positive correlation between the serum concentration of verapamil and the relative increase in average R-R interval was demonstrated.It is concluded that dosage t.d.s. with conventional tablets of verapamil or once daily with the slow release formulation gave the same antiarrhythmic efficacy over 24 h, and was associated with equal trough serum concentrations of verapamil.     

环磷腺苷葡胺、维拉帕米和硫酸镁三联转复心房颤动

目的　观察环磷腺苷葡胺、维拉帕米和硫酸镁三联疗法对持续性或慢性心房颤动 (房颤 )的转复作用及转复半年后窦律维持率。方法　治疗组静滴环磷腺苷葡胺、硫酸镁 ,静注或口服维拉帕米 ;对照组除心室率快及伴有心衰者静注毛花苷C外 ,其余均用安慰剂。结果　治疗组 34例转复率 73 5 3% ,对照组 34例转复率 8 8% ,两组比较差异有显著意义 (P <0 0 0 1)。治疗组总转复率达 72 3% ,半年窦律维持率 6 3 83%。结论　环磷腺苷葡胺、维拉帕米和硫酸镁三联疗法转复持续性或慢性房颤安全有效 ,半年窦律维持率亦较高。     

慢性心房颤动患者P-选择素水平及内皮功能障碍

目的研究慢性心房颤动 (房颤 )患者血小板活化和内皮功能障碍的有关标志物 ,探讨其临床意义。方法采用酶联免疫双抗体夹心法测定心脏病患者房颤组 (30例 )、无房颤组 (2 0例 )和正常对照组 (1 7例 )的血浆P 选择素 (P selectin)及血管性血友病因子 (vonWillebrandfactorvWF)的水平。结果房颤组血浆P 选择素及vWF水平显著高于无房颤组及正常对照组 (P均 <0 0 1 ) ,无房颤组与正常对照组比较上述指标亦增高 (P <0 0 1 )。结论慢性房颤组患者存在血小板激活和内皮功能障碍 ,这些异常可能参与了房颤患者血栓的形成     

贝那普利对瓣膜病心衰患者左室重塑及运动耐量的影响

目的观察血管紧张素转换酶抑制剂贝那普利对瓣膜病心力衰竭患者心室重塑和运动耐量的影响。方法选择瓣膜病心力衰竭患者60例,随机分为A组(对照组,28例)和B组(贝那普利组,32例)。A组采用洋地黄、利尿剂等常规治疗,B组在A组治疗的基础上加用贝那普利。测量治疗前和治疗后12个月患者6 min步行距离,心脏彩超测定左室舒张末径(LVEDD)、左室收缩末径(LVESD)、左室短轴缩短率(LVFS)。结果与常规治疗组相比,贝那普利组治疗12个月后LVEDD缩小[(53.2±6.1)mmvs(60.8±8.9)mm,P<0.01]、LVESD缩小[(44.5±6.9)mmvs(49.2±7.2)mm,P<0.01]、LVFS增加[(24.2±5.4)%vs(20.1±4.9)%,P<0.01],6 min步行距离增加[(430±88.2)mvs(398±75.9)m,P<0.05]。结论贝那普利可显著改善瓣膜病心力衰竭患者左室重塑,提高运动耐量。