Effects of ibutilide on spontaneous and induced ventricular arrhythmias in 24-hour canine myocardial infarction: a comparative study with sotalol and encainide.

The electrophysiologic and antiarrhythmic effects of ibutilide, sotalol, and encainide were compared in dogs 24 h after myocardial infarction. Ibutilide (0.03 to 0.3 mg/kg i.v.) prevented the induction of ventricular arrhythmias in 100% of the dogs that had demonstrated inducible ventricular arrhythmias prior to treatment. This antiarrhythmic action was associated with significant increases in ventricular refractoriness and monophasic action potential duration. Sotalol (1.0 to 10.0 mg/kg i.v.) increased the ventricular refractory period and monophasic action potential duration and prevented the induction of ventricular arrhythmias in 75% of the dogs that demonstrated inducible ventricular tachyarrhythmias at baseline. Although 10 mg/kg of sotalol was required to prevent the initiation of ventricular tachycardia, this dose produced marked cardiovascular depression and hypotension in 50% of the dogs tested. Neither ibutilide nor sotalol significantly decreased the incidence of spontaneous ventricular arrhythmias. The class IC agent encainide (0.3 to 3.0 mg/kg i.v.) was successful in preventing the induction of ventricular arrhythmias in only 20% of the dogs tested. However, in contrast to ibutilide and sotalol, encainide significantly reduced spontaneous arrhythmias. Atrial and ventricular refractoriness were significantly increased only after the highest dose of encainide tested (3.0 mg/kg). Over the dose ranges studied, the relative efficacy for prevention of pacing-induced ventricular arrhythmias was ibutilide greater than sotalol much greater than encainide. For suppression of spontaneous ventricular arrhythmias, the relative efficacy was encainide much greater than ibutilide = sotalol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of drug effects on spontaneous and induced ventricular arrhythmias in a 24-h canine infarction model

The antiarrhythmic efficacy of encainide, sotalol, flecainide and disopyramide was evaluated in anesthetized dogs subjected to 2-stage total occlusion of the left anterior descending coronary artery. Utilization of this canine model, while anesthetized, permitted the assessment of drug effects not only on uni- and/or multi-focal ectopic ventricular arrhythmias, but also on dysrhythmias associated with aberrant conduction or reentrant excitation pathways. The former was assessed by quantification of ectopic-to-total beat ratios while the later was determined by subjecting the animal to provocative stimuli which produced repetitive ventricular responses. At the cumulative i.v. doses studied, encainide (0.5-4 mg/kg), flecainide (1-8 mg/kg) and disopyramide (0.3-10 mg/kg), but not sotalol (2-8 mg/kg), effectively suppressed ventricular ectopic activity in a dose-related manner. In contrast, sotalol was highly effective in preventing the induction of reentrant ventricular tachyarrhythmias. Disopyramide was only modestly active, while flecainide and encainide had the least favorable profiles of effect in suppressing re-entry arrhythmias in this model. Based on these observations, the anesthetized Harris dog appears to represent a useful two-faceted in vivo model for use in the evaluation of potential antiarrhythmic agents.     

胺碘酮治疗急性心肌梗死合并室性心律失常的效果研究

目的探讨胺碘酮治疗急性心肌梗死合并室性心律失常的临床疗效。方法急性心肌梗死合并室性心律失常患者86例随机分为治疗组46例和对照组40例,治疗组出现室性心律失常后给予胺碘酮治疗,对照组出现室性心律失常后给予利多卡因治疗,比较2组临床疗效、再住院率及不良反应发生率。结果药物治疗后,治疗组起效时间短于对照组,有效率高于对照组,不良反应发生率及1年内再住院率低于对照组,差异均有统计学意义(P<0.05)。结论胺碘酮治疗室性心律失常,安全有效,值得临床推广。     

先兆子痫患者D-二聚体水平与24h尿蛋白定量的研究

目的分析先兆子痫患者D-二聚体水平与24h尿蛋白定量的相关性。方法入选的先兆子痫患者82例(观察组)和40例正常妊娠孕妇(对照组),运用免疫比浊法测定D-二聚体;运用散色比浊法测定24h尿蛋白定量。利用相关系数(r)来表示D-二聚体水平与24h尿蛋白定量的相关性,两组均数之间的比较采用t检验。分析比较两组D-二聚体水平与24h尿蛋白定量的相关性。结果先兆子痫患者D-二聚体水平与24h尿蛋白定量呈正相关性。结论正常妊娠孕妇随着孕期的增长,血清D-二聚体水平也随着增高,表明孕妇体内处于高凝状态及继发性纤溶活性增强。先兆子痫患者血清D-二聚体水平则明显增高,提示此类患者体内处于高凝状态及继发性纤溶亢进,并且可能存在慢性DIC。正常孕妇尿中蛋白可轻度增加,这与体位和肾流量加大、肾小球滤过率增加有关。两者综合观察,可更全面的掌握子痫的预后及发展。     

氧化苦参碱对急性心肌梗死大鼠左室重构的干预作用

目的 观察不同剂量氧化苦参碱(OMT)对急性心肌梗死(AMI)大鼠心室重构的防治作用.方法 SD大鼠30只均分5组,除假手术组外,其他4组采用结扎冠状动脉左前降支的方法复制大鼠AMI模型后,其中3组分别用三种剂量OMT灌胃,8周后检测心指数、心肌重构指数、胶原含量并进行病理组织学检查,分析心室重构的程度.结果 冠脉结扎8周后,模型组大鼠心室重构各项指标与假手术组相比差异有统计学意义(P<0.01);OMT各组大鼠心室重构各项指标与模型组相比差异有统计学意义(P<0.05或P<0.01).结论 OMT能够有效延缓心脏结构的变异,抑制胶原沉积,对AMI后心室重构具有一定的预防作用.     

大豆异黄酮对心肌梗死大鼠心室重构的影响(英文)

目的：观察大豆异黄酮对心肌梗死大鼠心室重构的影响。方法：雄性SD大鼠,结扎冠状动脉左前降支,造成心肌梗死。实验分为6组：假手术组,心肌梗死模型组,卡托普利组,大豆异黄酮低、中、高剂量组。在结扎冠状动脉后3h开始,分别灌胃给予0.5%羧甲基纤维素钠(CMC-Na),0.5%CMC-Na,卡托普利50mg·kg~(-1)和大豆异黄酮30,90,270 mg·kg~(-1),qd,共35 d。给药容积均为10 mL·kg~(-1)。最后一次给药后24 h,测定心率(HR)、左室舒张末期压(LVEDP)、左室收缩压峰值(Peak)、左室压最大上升速率/下降速率(±dp/dt_(max))和心肌最大缩短速率(V_(max)),测定全心室质量和体重比(TVW/BW),用天狼猩红染色,在图像分析系统下测量梗死范围(IS)、左心室内径(LVD)、室间隔厚度(ST),心肌间质胶原容积系数(ICVF)和血管周围胶原容积系数(PCVF)。结果：卡托普利、大豆异黄酮90 mg·kg~(-1)和270 mg·kg~(-1)组大鼠的梗死范围分别是(31±s4)%,(32±3)%和(31±5)%,均显著小于心肌梗死模型组大鼠[(38.9±2.9)%,P＜0.01]。心肌梗死组大鼠的TVW/BW,LVD,ICVF和PCVF均比假手术组明显增加(P＜0.01),增加的TVW/BW,LVD,ICVF和PCVF用卡托普利和大豆异黄酮90 mg·kg~(-1),270 mg·kg~(-1)治疗后明显减少[P＜0.01,P＜0.05(SI 90 mg·kg~(-1)组的LVD)]。心肌梗死大鼠的ST显著减小(P＜0.01),而给予卡托普利和大豆异黄酮可增加ST(P＜0.01)。结扎LAD后,大鼠的Peak,±dp/dt_(max)和V_(max)明显降低(P＜0.01),而LVEDP明显升高(P＜0.01),降低的Peak,±dp/dt_(max)和V_(max)在给予卡托普利、大豆异黄酮90 mg·kg~(-1)和270 mg·kg~(-1)后明显升高(P＜0.01)；而升高的LVEDP仅在给予卡托普利治疗后降低。结论：大豆异黄酮能够改善心肌梗死大鼠的心功能和心室重构。     

右室心肌梗死对急性下后壁心肌梗死预后的影响

目的 探讨右室心肌梗死对急性下后壁心肌梗死预后的影响.方法 对比分析自2002年2月～2006年2月在我院住院治疗的42例合并右室心肌梗死的急性下后壁心肌梗死(IWMI合并RVMI组)的患者与4JD例单纯下后壁心肌梗死(IWMI组)的患者,在住院期间及出院后病死率及心衰、心律失常等并发症发生率的差异.结果 经研究得出急性下后壁心肌梗死合并右室心肌梗死时与单纯急性下后壁心肌梗死对比,患者院内病死率(29%对5%,P＜0.01)及心律失常、心衰、心源性休克等主要并发症的发生率(67%对29%,P＜0.01)均明显高于单纯急性下后壁心肌梗死的患者.经1～4年随访,合并右室心肌梗死的患者出院后病死率(35%对16%,P＜0.05)及心衰、心律失常等并发症的发生率(75%对36%,P＜0.05)均明显增高.结论 合并右室心肌梗死的急性下后壁心肌梗死患者预后不良.     

静脉用药调配中心24h运行的设计与管理

通过介绍本院静脉用药调配中心（PIVAS）24h运作模式的设计与管理,特别是皮试医嘱、加急医嘱的设计与管理,为进一步完善PIVAS的临床服务功能提供经验。先进的信息化设计和严格的科学管理体系是PIVAS24h正常运行以及各项工作有序进行的有力保障。     

抗氧化治疗对防治急性心肌梗死患者远期心室重构的临床研究

目的：研究抗氧化剂普罗布考对防治急性心肌梗死血运重建患者远期心室重构的疗效。方法：符合纳入标准的急性ST段抬高型心肌梗死（STEMI）血运重建患者90例,按随机数字表法分为组①和组②。组①：常规冠心病二级预防治疗;组②：冠心病二级预防加"普罗布考"抗氧化治疗。观察指标：（1）各组患者住院期间及1年后心脏彩超结果;（2）各组患者住院期间及3个月后超氧化物歧化酶（SOD）检测结果。结果：（1）治疗前,组①和组②的基线资料、SOD水平及心脏彩超检查结果对比无差别（P>0.05）。（2）1年以后复查心脏彩超结果提示：组①相比于组②发生心脏扩大患者的比率更高（P<0.05）;（3）3个月后复查SOD水平,组①与前期对比无差异（P>0.05）。组②与前期对比SOD水平升高（P<0.05）。利用二元Logistic回归模型建立数值间线性关系,得出SOD表达水平与左室舒张末内径呈负相关（B=-0.042,P<0.05）。结论：氧化应激是导致心梗后进一步心室重构主要因素之一,抗氧化剂普罗布考对防治心肌梗死后心室重构的临床疗效显著,值得推广。     

卡维地洛对急性心肌梗死大鼠左室重构的影响

目的建立大鼠急性心肌梗死(acute myocardial infarction,AMI)模型,观察AMI后卡维地洛早期处理对心梗后左室重构的影响。方法雄性Wistar大鼠60只,随机分为假手术组(n=15)、AMI组(n=15)、低剂量卡维地洛组(n=15)和高剂量卡维地洛组(n=15)。建模后2周心肌组织取材,HE、Masson染色病理学检查;免疫组织化学测定心肌组织中毛细血管及抗凋亡、凋亡蛋白表达;建模前1 d及建模后2周心脏超声检查;采用Elisa法对建模前及建模后2周血浆脑钠肽(BNP)水平测定。结果建模后2周,与AMI组比较,卡维地洛组梗死面积减小,梗死区存活心肌细胞数增加,替代性纤维化面积减小,抗凋亡蛋白bcl-xl表达增强,凋亡蛋白Bax表达降低,P<0.05;梗死区及梗死旁区心肌组织中幼稚毛细血管密度增加,上述改变在高剂量药组明显;心脏超声左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、室间隔厚度(IVS)直线小,心率(HR)减慢,左室射血分数(EF)值增加(P<0.05);血浆BNP水平较AMI组明显降低(P<0.05)。结论大鼠AMI后早期应用卡维地洛处理,可减少心肌细胞的凋亡及丢失,减轻AMI后心肌梗死程度,减轻左心室重构,改善AMI后左室功能,延缓心力衰竭的发生。     

卡托普利对心肌梗死后左室重塑的影响

目的 探讨卡托普利(开搏通)与急性心肌梗死(AMI)后左室重塑的关系.方法 选择首次AMI患者70例,在发病后给予卡托普利治疗,应用彩色多普勒超声显像仪,于发病第4周和52周行超声心动图检查,观察左室形态、大小、室壁运动并记录左室收缩末期内径(LVDs)、舒张末期内径(LVDd)、左室收缩末期容积(LVESV)、左室舒张末期容积(LVEDV)、左室射血分数(LVEF)、左房内径(LAD)和二尖瓣血流频谱图中快速充盈E波最大流速(VE)和心房充盈A波最大流速(VA)等指标并计算VE/VA等指标.其中8例退出研究,将不规律应用卡托普利(n=29)和规律服用卡托普利(n=33)患者分为A、B 2组,比较52周时2组超声心动图观察指标.结果 B组的LVDs、LVDd、LVESV、LVEDV和LAD比A组降低,但LVEF和VE/VA比A组升高(P＜0.05).结论 卡托普利可以干预AMI后左室重塑,明显改善左室舒缩功能.     

吲达帕胺在逆转急性心肌梗死左室重构中的作用

目的：通过给急性心肌梗死患者应用吲达帕胺（Ｉｎｄ）,观察其在逆转急性心肌梗死左室重构中的作用。方法：选择急性心肌梗死患者１１６例,随机分为Ｉｎｄ治疗组和对照组（各５８例）。用脉冲多普勒超声心动图测定等容舒张时间（ＩＶＲＴ）、二尖瓣口血流频谱、肺静脉血流频谱和左室射血分数。结果：Ｉｎｄ治疗组与对照组比较：ＩＶＲＴ、ＥＤＴ和ＡＲ波时间明显缩短;Ｅ／Ａ比值、Ｓ／Ｄ波幅比值、Ｓ／Ｄ时间比值和ＥＦ明显升高;     

Effects of antidepressants on the intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation in the dog heart after myocardial infarction

Summary The effects of mianserin, a tetracyclic antidepressant, and adinazolam, a new triazolobenzodiazepine which has antidepressant activity, on intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation were studied in the dog heart after myocardial infarction and compared to the effects of amitriptyline, a standard tricyclic antidepressant.Amitriptyline at a dose of 1 mg/kg significantly slowed ventricular conduction in a frequency-dependent manner and at doses of 2 and 3 mg/kg significantly slowed ventricular conduction in infarcted ventricular myocardium. Amitriptyline also significantly slowed ventricular conduction in normal myocardium. Amitriptyline increased the incidence of ventricular arrhythmias induced by the programmed ventricular stimulation and prolonged the intraventricular delayed conduction resulting in re-entrant ventricular arrhythmia.On the other hand, mianserin and adinazolam at doses of 1–3 mg/kg had no significant effects on intraventricular conduction in infarcted and normal myocardium and on the incidence of arrhythmias induced by programmed ventricular stimulation. From these results, we can expect that mianserin and adinazolam may have a much lower cardiac toxicity than amitriptyline. Send offprint requests to M. Nishimoto at the above address     

Comparative study of the effects of flurazepam and nitrazepam on sleep by 24-hour polygraphy

Summary A new method, 24-hour polygraphy (EEG, EMG, and EOG), was applied not only to investigate the influence of hypnotics on night sleep, but to examine the precise influence on sleep-wake-fulness rhythm the day following administration. The hypnotics used were flurazepam 15 mg and nitrazepam 5 mg. The subjects were healthy volunteers, 5 men and 4 women, aged 20–50 years. The polygraphic record was made three times for each subject. Flurazepam prolonged sleep time (%) significantly (p<0.05), shortened sleep latency (p<0.05), decreased waking period (p<0.05), and increased the percentage of Stage 2 sleep (p<0.1) in comparison to nitrazepam. Flurazepam 15 mg appears to be a better hypnotic than nitrazepam 5 mg, but caution is required in its use because of a greater residual sedative effect on the following day. Some nondrug factors affecting sleep and a method for detecting the residual effect of hypnotics are discussed.     

Advances in the pharmacologic treatment of ventricular arrhythmias

Introduction: Despite many advances in nonpharmacologic management of ventricular arrhythmias, antiarrhythmic drugs remain important in both the acute conversion and chronic prevention of ventricular arrhythmias.

Areas covered: Key trials related to antiarrhythmic drug use are reviewed, emphasizing the impact of recent discoveries. Sodium channel blockers are discussed with an emphasis on recently identified specialized uses. Beta blockers, amiodarone, sotalol, and dofetilide are discussed together in the context of structural heart disease, because they do not increase mortality in this group of patients. Other medications found to reduce ventricular arrhythmia burden are discussed last.

Expert opinion: Since most patients with ventricular arrhythmias have structural heart disease, pharmacologic treatment is limited to amiodarone, d-,l-sotalol, and dofetilide (off-label indication), in conjunction with defibrillator implantation. While amiodarone has superior reduction in arrhythmias, its long-term extracardiac toxicities can cause significant morbidity. A trial of sotalol is reasonable if there are no contraindications, recognizing that over 20% of patients have to discontinue it because of adverse effects. Beta blockers are first line therapy for most patients. Genetic testing is particularly informative regarding treatment approach in long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic VT. Research should continue to focus on developing more effective antiarrhythmic medications with less long-term toxicity.     

Effects of DPI 201-106, a novel cardiotonic agent,on hemodynamics,cardiac electrophysiology and arrhythmias induced by programmed ventricular stimulation in dogs with subacute myocardial infarction: A comparative study with dobutamine

Summary DPI 201-106 (DPI), a novel and potent cardiotonic agent, exhibits its effects by prolonging the open state of Na⁺ channels, resulting in an increase in action potential duration, and thus, is supposed to share the class III antiarrhythmic activity. The effects of DPI on the hemodynamics, intraventricular conduction and refractoriness of heart, and the incidence of arrhythmias induced by programmed electrical ventricular stimulation (PES) were compared with (±)-dobutamine. Dogs which survived for 5 to 7 days after the induction of myocardial infarction were used as the model. The presence of sub-acute myocardial infarction caused by occluding the left anterior descending coronary artery elicited a mild left ventricular dysfunction represented by a significant decrease in peak LV dp/dt by about 20%.Both i.v. bolus injection of DPI (1, 3 and 5 mg/kg) and i. v. continuous infusion of dobutamine (3, 5 and 10 g/kg/min), which were administered in a cumulative manner, dose-dependently improved the hemodynamic parameters. At the higher doses of both DPI (3 and 5 mg/kg) and dobutamine (5 and 10 g/kg/min) the control values were reached or even exceeded. DPI dose-dependently increased the effective refractory period (ERP) of both non-infarcted and infarcted ventricular myocardia to a similar degree, but the conduction time showed a frequency-dependent increase in the infarcted myocardium to a greater degree than in the non-infarcted myocardium after DPI. In contrast, dobutamine decreased the ERP in both non-infarcted and infarcted myocardia, and slightly increased the difference of refractoriness between the non-infarcted and infarcted zones with no effect on the intraventricular conduction. In the PES study, DPI (3 and 5 mg/kg) produced a significant decrease in the incidence of ventricular tachycardia, whereas dobutamine (5 and 10 g/kg/min) tended to worsen the arrhythmias. These findings suggest that cardiotonic agents with a class III antiarrhythmic property such as DPI may be potentially useful for the management of heart failure accompanied by ischemic heart disease.Abbreviations DPI, DPI 201-106; PES programmed electrical ventricular stimulation - LV dp/dt the rate of rise of left ventricular pressure - ERP effective refractory period - RVOT right ventricular outflow tract - VT ventricular tachycardia - LAD left anterior discending coronary artery Send offprint requests to T. Uematsu at the above address     

Effects of an olmesartan medoxomil based treatment algorithm on 24-hour blood pressure control in patients with hypertension and type 2 diabetes

Abstract

Objective:

The BENIFICIARY (BENIcar safety and efFICacy evaluatIon: An open-label, single-ARm, titration study in patients with hypertension and tYpe 2 diabetes) study was conducted to evaluate the efficacy and safety of olmesartan medoxomil (OM) plus hydrochlorothiazide (HCTZ) in patients with hypertension and type 2 diabetes.     

心脏和肾脏短暂缺血对心肌梗死后心律失常的影响

目的　研究心脏和肾脏短暂缺血预处理对急性心肌梗死(AMI)后心律失常的影响。方法　观察AMI组(A组)、心脏缺血预处理(MIP)组(B组)和肾脏缺血预处理(RIP)组(C组)新西兰兔在AMI前后的心律失常情况及QT间期离散度(QTd) ,并行心内电生理诱发室性心动过速(VT) ,对三组的指标进行比较,同时设置假手术组(D组)作对照。结果　四组在手术前心律失常及QTd差异无显著意义(P >0 . 0 5 ) ;D组手术前后心律失常及QTd比较差异无显著意义(P >0 . 0 5 ) ;在AMI后,B、C两组室性心律失常及QTd明显小于A组(P <0 . 0 5 ) ,而B、C两组室性心律失常及QTd比较差异无显著意义(P >0 .0 5 )。结论　MIP和RIP均可减少AMI后室性心律失常的发生,而且两者的作用没有明显差异。     

盐酸普罗帕酮终止心梗后持续性室速的特征及其机制

目的 观察普罗帕酮终止心梗后持续性室速的特征及其机制。方法 32例陈旧性心梗后持续性室速患者在基线治疗基础上室速时应用普罗帕酮70mg在20min内静脉推注,根据能否终止室速分为有效组和无效组,观察心率、血压、心电图QRS时程的变化及室速的终止方式。结果 有效组普罗帕酮应用前后QRS间期明显增宽（P〈0.01）;心室率明显减低（P〈0.01）,无效组普罗帕酮应用前后QRS间期及心室率变化不明显（P〉0.05）。27室速终止患者中25例患者为室速突然中止占92.6%（25/27）,2例患者逐渐终止占7.4%（2/27）;应用普罗帕酮后无论是有效组还是无效组,血压较应用前都有所下降（P〈0.05）。结论 普罗帕酮作可以有效地终止心梗后持续性室速,其有效的特征是QRS间期明显增宽,心室率明显减低,识别普罗帕酮是否有效的特征对于避免过量用药及抗心律失常药物的选择具有重要意义。