普罗帕酮和普鲁卡因胺抗犬缺血性快速室性心律失常的对比研究(英文)

目的　观察普罗帕酮对犬在体心脏缺血性快速室性心律失常的心电生理影响并与普鲁卡因胺对比 ,以探讨其抗缺血性快速室性心律失常的效果及作用机制。方法　用冠状动脉左前降支结扎并部分再灌注法造成犬急性前壁心肌梗死 ,5～ 8d后 ,辅以心室程控电刺激 (PES)技术及冠状动脉内恒定微量直流电刺激技术 ,并诱发与终止持续性室性心动过速和心室纤颤 ,制备成犬急性心肌缺血再灌注后可控性快速室性心律失常的在体心脏心电模型 ,心电图对比观察普罗帕酮及普鲁卡因胺的抗心律失常作用。结果　普罗帕酮及普鲁卡因胺均能显著地延长心肌梗死犬的心电图QTc间期 (P <0 .0 1 )及正常和缺血心肌的有效不应期 (P <0 .0 1 ) ,降低缺血心肌和左室心肌的有效不应期离散度 (P <0 .0 1 ) ,提高正常心肌和缺血心肌的舒张期兴奋阈值 (P <0 .0 1 ) ,抑制PES诱发的持续性室性心动过速和心室纤颤 (P <0 .0 1 ) ,并能预防犬急性心肌梗死后再次缺血所致的自发性室性心动过速和心室纤颤 (P <0 .0 5)。结论　①该犬在体心脏心电药理学实验模型具有较好的重复性、可靠性及临床相关性 ,是一种有价值的心电药理学实验研究模型。②普罗帕酮及普鲁卡因胺均具有抗缺血性快速室性心律失常的心电生理作用 ,是有效的抗颤药物 ,两药效果相似     

胺碘酮与心律平对阵发性心房颤动疗效的比较

目的：对比观察胺碘酮和心律平治疗阵发性心房颤动的疗效与安全性。方法：56例频繁发作的阵发性房颤患随机分为胺碘酮组(28例)和心律平组(28例)。胺碘酮用法为：0．2g，每天3次，7～10d；0．2g，每天2次，1wk；维持量0．2g，每天1次或0．2g，每2天1次。心律平：0.15g，每天3次或0．15g，每天4次，14d；维持量0．1g，每天3次。服用负荷量期间每周就诊1次，维持量期间每月就诊1次。结果：随访6mon，胺碘酮组和心律平组分别有4例和2例因出现难以耐受的副作用而终止治疗，无危及生命的副作用。胺碘酮组总有效率82．1％，心律平组为57．1％(P＜0．05)。结论：胺碘酮对阵发性心房颤动的疗效高于心律平，但其长期疗效可能会受到心脏外副作用的影响。     

静脉注射心律平与顿服心律平转复房颤疗效及安全性比较

关键词 房颤 心律平 顿服 文摘 目的 观察监测临床广泛应用的静脉输注心律平转复房颤的患者,是否能安全院外处方顿服心律平转复房颤。方法 临床入选>阵发房颤患者,随机分为两组静脉负荷量心律平组和口服负荷量心律平组,对成功转复的患者院外处方顿服心律平治疗,比较两组转复率、副作用发生率、急诊就诊率 结果两组首次顿服心律平发生副作用（8.9%vs5.7%,p>0.05）,无统计学差异.而院外顿服负荷量心律平治疗副作用发生率（8.9%vs1.25%,p<0.05）,急诊就诊率（19.0%vs5%,p<0.001）,据统计学差异。结论患者首次转负房颤,宜院内口服负荷量,发生副作用可及时处理,保证患者安全,即使能耐受静脉冲击量心律平转复房颤,也不能预测顿服心律平不良反应的发生。     

随机对照观察进口普罗帕酮治疗室性早搏的疗效和安全性

目的评价进口普罗帕酮治疗室性早搏的疗效及安全性.方法采用随机分组、美西律平行对照的方法,对其进行了研究;入选患者共107例,男性47例,女性60例,年龄为(45.8±12.4)a,进口普罗帕酮组71例,其中男性34例,女性37例,年龄为(45.3±13.5)a;美西律组36例,男性13例,女性23例;年龄为(46.8±10.0)a.结果进口普罗帕酮组的有效率为54.9%;美西律组的有效率为66.6%;2组有效率经χ2检验P＞0.05,无统计学意义;进口普罗帕酮组治疗前后P-R间期经t检验,延长有统计学意义(P＜0.05),对ECG的其他指标在治疗前后均无统计学意义(P＞0.05);美西律组在治疗前后对ECG的各指标无统计学意义(P＞0.05).2组治疗前后ECG各指标的改变经t检验无统计学意义(P＞0.05).进口普罗帕酮组不良反应的发生率为14.1%,与心脏有关的不良反应6例,占不良反应的60%;美西律组有3例出现不良反应,发生率为8.3%,未观察到与心脏有关的不良反应;2组均无死亡及因心脏不良反应出现严重的事件;经χ2检验,2组不良反应发生率无统计学意义(P＞0.05).未发现肝、肾功能损害.结论服用进口普罗帕酮600 mg@d-1(含600 mg@d-1)以下治疗室性早搏,有效、安全,但由于病例较少,结果仅供参考.     

Flecainide: long-term effects in patients with sustained ventricular tachycardia or ventricular fibrillation.

Efficacy of flecainide was investigated in 50 patients with sustained ventricular tachycardia (n = 38) or ventricular fibrillation (n = 12) during a 4-week in-hospital and 1-year follow-up period. Furthermore, the predictive value of programmed electrical stimulation, Holter monitoring, and exercise testing on outcome of long-term treatment was studied. Etiology of the tachyarrhythmia was coronary artery disease in 37 patients and other etiologies in 13 patients. The success rate of flecainide after 1 year, based on intention to treat, was 54%. The success rate during the in-hospital phase was 84% (in six patients flecainide was discontinued because of tachyarrhythmia and in two because of side effects). Calculated after 4 weeks hospitalization, the success rate was 78% for patients with tachyarrhythmias based on coronary artery disease and 55% for patients with tachyarrhythmias based on other etiologies (11 patients showed recurrences and two patients severe side effects). Patients with tachyarrhythmias based on coronary artery disease showed a lower ejection fraction and earlier recurrence than patients with arrhythmias based on other etiologies. Proarrhythmic effects developed in six patients (12%). Electrophysiological evaluation was performed in 28 patients at baseline and after intravenous flecainide. Negative predictive value of the electrophysiological evaluation after intravenous flecainide for patients with inducible tachyarrhythmias at baseline (n = 21) was 40%. For Holter monitoring (n = 24) this value was 86%. Non-ischemia-related induction of tachycardia by exercise was present in two of 30 patients on flecainide; both patients showed recurrence of the tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacologic response of cesium-induced ventricular tachyarrhythmias in anesthetized dogs.

Cesium chloride administration causes ventricular tachyarrhythmias in dogs, with many of the features of the clinical long QT syndrome. We developed a model of cesium-induced arrhythmias, using loading and maintenance doses of cesium to produce continuous cesium effects. The purpose of the present experiments was to study the response of arrhythmias in this model to a variety of pharmacologic interventions. Cesium chloride caused ventricular tachyarrhythmias that either degenerated to ventricular fibrillation (VF) or remained stable for greater than 30 min. Cesium-induced arrhythmias were suppressed by the calcium antagonist diltiazem, magnesium chloride, beta blockade (with atenolol), or vagal nerve stimulation--all interventions that can suppress calcium entry. beta-Adrenergic stimulation with isoproterenol initiated ventricular arrhythmias in the presence of subarrhythmic doses of cesium. Sodium channel blockers (lidocaine and high concentrations of quinidine) also suppressed cesium-induced arrhythmias. Intravenous (i.v.) bolus doses of isotonic saline solution at times corresponding to the other interventions studied did not alter the severity of cesium-induced arrhythmia. We conclude that cesium-induced ventricular arrhythmias in this model are suppressed by agents that reduce transmembrane calcium currents as well as by high doses of sodium channel blockers. These findings may have relevance to the mechanisms of, and the therapeutic approach to, the clinical long QT syndrome.     

Effects of propafenone on calcium current in guinea-pig ventricular myocytes.

1. The modulation of L-type voltage-sensitive calcium channels in guinea-pig isolated ventricular myocytes by propafenone was examined by the whole cell voltage-clamp technique. 2. Propafenone, 10(-7) -5 x 10(-5) M, produced a concentration-dependent inhibition of Ca current (ICa) without any significant change in the current-voltage relation. Half-blocking concentration (IC50) of propafenone for the peak ICa at +10 mV was 5 x 10(-6) M. 3. The voltage-dependence of ICa inactivation was shifted in the hyperpolarizing direction in the presence of 5 x 10(-6) M propafenone. 4. A frequency-dependent relative block by propafenone was observed after repetitive depolarizing test pulses at a frequency of 0.5 and 1 Hz. The recovery of ICa from inactivation was prolonged by propafenone and the reactivation exhibited an additional exponential component attributed to the slow release from drug block of Ca channels. 5. These results suggest that propafenone, at therapeutic concentrations exhibits Ca channel blocking properties that may be involved in its antiarrhythmic mechanism.     

Efficacy of esmolol in the treatment and transfer of patients with supraventricular tachyarrhythmias to alternate oral antiarrhythmic agents

The efficacy and safety of esmolol, a titratable intravenous beta-adrenergic blocking agent with a short elimination half-life (t 1/2 = 9.0 min) was evaluated in a multicenter open-label study for the treatment of supraventricular tachyarrhythmias (heart rate greater than 100 bpm). The study also investigated the feasibility of transferring patients from esmolol to alternate oral antiarrhythmic agents without loss of therapeutic response. Of the 113 patients studied, 95 (84%) achieved therapeutic response (reduction in heart rate of 15% or more or conversion to sinus rhythm). Most of these patients (93%) achieved the therapeutic response at esmolol doses of 200 micrograms/kg/min or lower. Transfer from esmolol to an oral antiarrhythmic agent(s) was studied in 76 patients. Alternate antiarrhythmic agents used in this study were digoxin (N = 25), propranolol (N = 21), verapamil (N = 10), metoprolol (N = 11), quinidine (N = 2), and a combination of two antiarrhythmic agents (N = 7). Sixty-seven (88%) patients were successfully transferred to oral antiarrhythmic agents without loss of the therapeutic response obtained with esmolol. The most frequent adverse effect observed during the study was hypotension, which resolved quickly (16 +/- 14 min) either by decreasing the dose or by discontinuation of esmolol infusion. This study supports previous observations concerning the safety and efficacy of esmolol in the treatment of supraventricular tachyarrhythmias. Furthermore, it demonstrates that the majority of patients successfully treated with esmolol can be safely and effectively transferred to oral therapy with alternate antiarrhythmic agents.     

The influence of CYP2D6 polymorphism on the antiarrhythmic efficacy of propafenone in patients with paroxysmal atrial fibrillation during 3 months propafenone prophylactic treatment

OBJECTIVE: Propafenone (PPF) is an antiarrhythmic, Class Ic agent. Its metabolism is genetically controlled by a cytochrome P450 isoenzyme named CYP2D6, which shows polymorphism in human population. The aim of this paper was to determine the correlation between the antiarrhythmic efficacy of PPF and the oxidation phenotype. SUBJECTS AND MATERIAL: The study group consisted of 42 patients, aged 36 to 75 years, suffering from paroxysmal atrial fibrillation (AF). The oxidation phenotype was described by the metabolic ratio (MR) of sparteine. The MR value separated the group of poor metabolizers (MR > 20) from the group of extensive metabolizers (MR < 20) with the subgroup of very extensive metabolizers (MR < 1). METHOD: The study was conducted during a 3-month PPF therapy for the prophylaxis of paroxysmal atrial fibrillation. PPF was given orally, 300-450 mg/day. The oxidation phenotype was checked prior to the administration of PPF. Serum concentration of PPF at 7, 11 days and the end of PPF therapy were determined. Statistical analysis of data was performed with the chi2 test and the Pearson's correlation methods. RESULTS: In the group of 42 patients, PPF therapy was 100% effective in poor metabolizers (PM). In extensive metabolizers (EM), 61% efficacy was observed with efficacy 0% in very extensive metabolizers (VEM). The correlation between oxidation phenotype and the ability to maintain sinus rhythm (SR) was statistically significant (r = 0.414, p < 0.05). CONCLUSIONS: The antiarrhythmic efficacy of propafenone depends on the oxidation phenotype; 100% efficacy occurred in the group of poor metabolizers whereas PPF, at the dose tested, was ineffective in very extensive metabolizers.     

槐定对犬缺血性快速室性心律失常及心梗后自发性室颤电生理变化的影响

用心脏程控刺激技术(PES),研究了ⅳ槐定对慢性心肌梗塞犬的正常心肌和梗塞心肌的电生理及快速室性心律失常的影响,并与普鲁卡因胺对比。两药均可显著延长OTc间期,RERP,NERP及IERP,缩小IDR和VDR,提高DET,抑制PES诱发的VT或VF,槐定尚可预防犬心肌梗塞后由急性心肌缺血所致的自发性室颤,证实了槐定抗缺血性快速室性心律失常的作用。     

经皮冠状动脉腔内成形术治疗老年冠心病的近期和远期疗效观察

目的　探讨经皮冠状动脉腔内成形术 (PTCA)和支架术治疗老年冠心病患者的近期和远期疗效。方法　连续 2 5 0例冠心病患者 32 1处病变行 PTCA治疗 ,依年龄分为 >6 5岁组 (10 2例 )和≤ 6 5岁组 (14 8例 )。观察手术成功率和住院期并发症。术后每 3～ 4个月定期临床随访 ,如有心肌缺血可疑表现 ,则重复冠脉造影检查 ,如发现再狭窄≥ 70 %则再次进行介入治疗 ,记录再次靶血管重建 (TL R)、总心脏事件和无心脏事件存活率。结果　与≤6 5岁组相比 ,>6 5岁组的女性、糖尿病、高血压病、三支血管病变较多见。两组手术成功率相似 ,分别为 91.2 %和92 .1% (P>0 .0 5 )。随访 6个月两组患者再次靶血管重建 (TL R)、总心脏事件和无心脏事件存活率均相似。结论　经皮冠状动脉腔内成形术 (PTCA)和支架术治疗老年冠心病患者的近期疗效和远期预后良好 ,与年龄无明显关系。     

Effects of propafenone on calcium currents in single ventricular myocytes of guinea-pig.

1. The effects of propafenone on the inward calcium current (ICa) were investigated in isolated single ventricular myocytes of the guinea-pig by the whole-cell clamp method. Propafenone inhibited ICa in a dose-dependent manner at concentrations of propafenone ranging from 1 x 10(-8) to 1 x 10(-3) M and half maximal block of ICa occurred at a propafenone concentration of 1.5 x 10(-6) M. Propafenone did not change the current-voltage relation of ICa other than a reduction in amplitude and showed no clear use- or frequency-dependent effects upon ICa (stimulation frequencies from 0.03 to 2 Hz). Propafenone did not alter the steady-state inactivation process: the half maximal activation potentials were 18.5 +/- 2.2 mV in the control state and 20.9 +/- 5.0 mV in the presence of 1 x 10(-6) M propafenone (n = 12, NS). Propafenone (1 x 10(-6) M) increased the half-time of reactivation by 73.9% (n = 6, 212.3 +/- 1.2 ms vs 369.2 +/- 1.5 ms, P < 0.05). 2. We conclude that propafenone blocks ICa in a concentration-dependent and a channel state-, use- or frequency-independent manner. The ICa blockade elicited by propafenone at clinically therapeutic plasma concentration is significant and may be involved in its anti-arrhythmic effects.     

CYPD6＊10基因型对中国室性心律失常病人普罗帕酮药效学的影响

AIM: To determine the effect of CYP2D6*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia. METHODS: Seventeen Chinese patients with ventricular premature contractions (VPC> or =1000/d) were recruited. They were normal in routine laboratory testing and administered propafenone hydrochloride 450-600 mg per day in three divided doses. Twelve lead cardiogram and 24 h Holter monitoring were performed before and after 7 d treatment of propafenone. Steady-state peak and trough concentrations of propafenone were measured by HPLC method. CYP2D6*10 genotypes of patients were assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Total inhibitory rate of VPC was 79.9 % in 17 patients with ventricular arrhythmia after propafenone treatment. PR interval prolongation was increased from 0.146 s+/-0.018 s to 0.161 s+/-0.022 s (P<0.05). CYP2D6 genotypes played an important role in plasma levels and effects of propafenone. In 450 mg/d group, patients with homozygous mutant of CYP2D6*10 not only had a Cmax of propafenone two times as high as those of wild-type genotype, but also showed a two fold higher inhibitory rate of VPC compared with those with homozygous CYP2D6*1 (P<0.05). CONCLUSION: CYP2D6*10 genotype is relevant to decreased activity of CYP2D6 enzyme in Chinese patients. Elevated plasma concentration is consistent with better efficacy of propafenone in patients with ventricular arrhythmia.     

长效利培酮微球治疗精神分裂症的远期疗效研究

目的探讨长效利培酮微球对精神分裂症的远期临床疗效和安全性,以及对血清催乳素的影响。方法于2007年至2009年间入选56例精神分裂症患者,随机分入长效利培酮微球（RLAI）研究组和利培酮口服液（ROS）对照组进行为期1年的治疗,分别以痊愈率、缓解率、停药率、复发率和再住院率进行评价,评定两组的临床总体印象-严重度（CGI-S）与个人和社会功能评分（PSP）量表,并测定血清催乳素水平,以χ2检验和t检验进行统计分析。结果至研究终点时,RLAI组的临床治愈率和缓解率均高于ROS组,无停药、复发或再次住院发生,临床总体印象与个人和社会功能评分改善均优于ROS组。RLAI组血清催乳素水平及总体不良反应发生率均明显低于ROS组（P〈0.05）。与ROS组相比,RLAI组无1例发生不依从（P〈0.05）。结论长效利培酮微球的远期疗效、安全性及治疗依从性均优于利培酮口服液,适用于维持治疗。     

宁心宝胶囊联合普罗帕酮治疗室性心律失常的临床研究

目的观察宁心宝胶囊联合普罗帕酮治疗室性心律失常的安全性与有效性。方法选取2016年7月—2017年7月于重庆市巴南区人民医院治疗的室性心律失常患者151例,随机分成对照组(75例)和治疗组(76例)。对照组患者口服盐酸普罗帕酮片,6片/次,3次/d;治疗组患者在对照组基础上口服宁心宝胶囊,2粒/次,2次/d。两组患者连续治疗2个月。观察两组患者临床疗效,同时比较治疗前后两组患者动态心电图指标、心功能指标和不良反应情况。结果治疗后,对照组和治疗组临床有效率分别为85.33%和96.05%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者QRS波时限、室性早搏及短阵室速较治疗前显著降低(P0.05),且治疗组这些动态心电图指标明显低于对照组(P0.05)。治疗后,两组患者6min步行距离和左心室射血分数(LEVF)水平较治疗前显著升高(P0.05),脑尿钠肽(BNP)水平显著降低(P0.05),且治疗组这些心功能指标明显好于对照组(P0.05)。治疗期间,治疗组患者药物不良反应发生率为3.95%,显著低于对照组患者的14.67%,两组比较差异具有统计学意义(P0.05)。结论宁心宝胶囊联合普罗帕酮治疗室性心律失常效果显著、安全性高,且能够显著改善患者心功能,具有一定的临床推广应用价值。     

普罗帕酮在心律失常患者中的代谢

目的：考察普罗帕酮（ＰＰＦ）在心律失常患者人群中存在的代谢差异，方法：用高效液相色谱法测定心得失常患者药后体内的ＰＰＦ和５－羟普罗帕酮（５－ＯＨＰ）的血药浓度。结果 在各剂量组中５－ＯＨＰ和ＰＰＦ的稳态谷值均具有较大的个体差异，随着剂量的增加ＰＰＦ血浓呈线性增加，而５－ＯＨＰ浓度变化较小，结论：约有４．６％患者的５－ＯＨＰ血浓超过ＰＰＦ，低剂量组中５－ＯＨＰ的体内积聚为明显，本研究中弱代谢的发生率     

Effects of a long-term treatment with alacepril on left ventricular hypertrophy and function in patients with essential hypertension.

The authors examined the effects of a long-term treatment with the angiotensin-converting enzyme inhibitor, alacepril, with respect to the reversal of left ventricular hypertrophy and the improvement of left ventricular function. Ten uncomplicated essential hypertensive patients with left ventricular hypertrophy, aged 53 +/- 8 years, were treated with alacepril alone for 12 months. All patients underwent echocardiography to to assess left ventricular dimensions and function before and after the treatment. After the treatment, blood pressure was decreased significantly from 163 +/- 14.1/98 +/- 4.2 to 142 +/- 20.3/86 +/- 11.0 mm Hg (each, P less than .01), whereas heart rate did not change (66 +/- 6 versus 69 +/- 8 beats/min). The left ventricular mass index was decreased significantly from 146 +/- 27 to 119 +/- 29 g/m2 (P less than .01). Ejection fraction, fractional shortening, peak shortening rate, and peak lengthening rate all improved significantly after the treatment. There was a significant inverse relationship between fractional shortening and end-systolic wall stress before the treatment (r = .63, P less than .05), and this relationship did not change after the treatment. It is concluded that alacepril improved both left ventricular systolic and diastolic function without causing any consistent augmentation of left ventricular contractility.     

Effect of long-term cimetidine treatment on left ventricular function in haemodialysis patients with active hyperparathyroidism.

1 The effect of long-term oral cimetidine on left ventricular function was evaluated in chronic haemodialysis patients with active hyperparathyroidism. 2 Radionuclide ventriculography (seven patients) and echocardiography (five patients) revealed a significant increase in ejection fraction and mean velocity of circumferential fibre shortening six months after treatment. 3 The improved cardiac performance was associated with improvement of bone histology. C-terminal parathyroid hormone, serum calcium, and mean arterial pressure changed little after treatment. 4 The improved cardiac performance is thought to be related to the suppression of uraemic hyperparathyroidism by cimetidine. 5 The present study suggests that uraemic hyperparathyroidism may play an important role in "uraemic cardiomyopathy".