增窦复脉颗粒抗缓慢性心律失常的实验研究

目的 观察中药复方制剂增窦复脉颗粒对实验性缓慢性心律失常的疗效.方法 取家兔随机均分成7组,各组分别按剂量灌胃给药,1次/天,连续7 d,末次药后30 min,用20%乌拉坦5 ml·kg-1麻醉,记录不同时间段心电变化及采用生物信号采集处理系统的全程动态监控,观察实验药物对动物的心率、P-R间期、QRS波时间、出现心律失常及心律失常的持续时间和出现传导阻滞等指标的影响.结果 增窦复脉颗粒对普萘洛尔所诱导的缓慢性心律失常模型家兔有明显的加快心率,缩短P-R间期、QRS波时间,减少心律失常和传导阻滞的发生率的作用.结论 增窦复脉颗粒能够有效地治疗普萘洛尔导致的缓慢性心律失常.     

蟾酥对豚鼠心脏电生理的影响

目的探讨蟾酥对豚鼠心脏的急性毒性。方法豚鼠一次性ig给予蟾酥125和250 mg·kg-1,记录心电图并监测左心室内压力上升最大速率(dp/dtmax),最大收缩压(Pmax),心率血压乘积(RPP)和心室最小舒张压(Pmin)。结果蟾酥使豚鼠心电图发生显著改变;与正常对照组P-R间期(27.8±5.1)ms相比,蟾酥125和250 mg·kg-1组显著延长,分别为44.5±7.2和(57.1±8.9)ms(P<0.01);蟾酥也引起心电图QRS时程增宽和心率加快;dp/dtmax,Pmax和RPP显著下降以及Pmin显著升高(P<0.05)。与阳性对照地高辛300mg·kg-1相比,蟾酥组P-R间期,QRS时程,dp/dtmax,Pmax,RPP和Pmin无显著性差异,但心率显著增快(P<0.01)。结论蟾酥导致豚鼠心律失常和心功能下降。     

高龄慢性心衰伴心律失常实施胺碘酮治疗临床观察

目的:观察高龄慢性心衰伴心律失常实施胺碘酮治疗临床效果.方法:回顾性分析242例高龄慢性心衰伴心律失常患者的临床资料,根据是否实施胺碘酮治疗进行分组;在基础性治疗、抗心衰治疗的基础上,对照组采取利多卡因治疗;观察组实施胺碘酮治疗;以室性前期收缩频次、短阵室速、PR间期、QRS波时限、QTc间期等疗效观察指标.结果:观察组室性前期收缩频次、短阵室速、PR间期、QRS波时限、QTc间期均优于对照组,心脏事件、药物不良反应发生率均小于对照组,复律时间短于对照组,差异显著(P<0.05).结论:高龄慢性心衰伴心律失常实施胺碘酮治疗的临床效果显著,可加快心脏复律,对于缓解症状、改善预后均具有积极作用,且安全性高,值得推广.     

异丙酚对大鼠离体心脏再灌注心律失常的影响

目的：实验观察异丙酚对大鼠离体心脏再灌注心律失常的影响。方法：SD大鼠Langendorff离体心脏灌注后,建立冠状动脉左前降支局部心肌缺血和再灌注心律失常模型。分6组：对照组;异丙酚1μg/ml组;异丙酚3μg/ml组;维拉帕米10ng/ml组;异丙酚1μg/ml加维拉帕米10ng/ml组;异丙酚3μg/ml加维拉帕米10ng/ml组。定时测量冠脉流量、心率和连续监测ECG,以比较各组再灌注期室性期前收缩（VPB）、心室纤颤（VF）、室性心动过速（VT）的发生率以及正常窦性节律（NSR）的持续时间。结果：与对照组相比,后4组再灌注期的VF发生率均有非常显著地降低（P＜0．01）,VF的持续时间显著缩短（P＜0．01）,NSR的时间明显延长,而VT的发生率仅有下降趋势。结论：3μg/ml的异丙酚与10ng/ml的维拉帕米相似,对大鼠离体心脏再灌注期VF的发生率和持续时间具有非常显著的抑制作用。     

四丙酰关附醇胺的抗心律失常作用及其与关附甲素的比较

在几种动物模型上观察了四丙酰关附醇胺(TPGFA)的抗心律失常作用. TPGFA使引发室性早搏，室性心动过速和心室纤颤所需乌头碱用量增加50%的剂量分别为1.6，1.4和1.8 mg·kg^-1；TPGFA 2 mg·kg^-1可提高豚鼠心脏毒毛花苷G中毒的耐受量和家兔心脏电致室颤阈；TPGFA还降低CaCl₂诱发的大鼠室颤发生率和死亡率，以及麻醉大鼠心脏冠脉结扎—再灌性室性心动过速和室颤的发生率. TPGFA的上述抗心律失常作用较关附甲素强. TPGFA显著延长大鼠心电图的QT_c间期，而对P-R间期和QRS时程影响不明显. 小鼠iv TPGFA的LD₅₀为42 mg·kg^-1.     

阿司咪唑对小鼠心脏的急性毒性研究

目的　通过观察小鼠心电图的变化,研究阿司咪唑对心脏的急性毒性,了解其致心律失常的类型,推测其致心律失常的机制。方法　用不同剂量的阿司咪唑对小鼠灌胃,分别记录不同时间的心电图变化。结果　阿司咪唑使多数小鼠心率减慢,P-R间期和Q-T间期延长,随剂量增加,甚至可引起完全性房室传导阻滞和窦性停搏。少数情况也会出现窦性、室性心动过速等快速性心律失常。结论　阿司咪唑可引起小鼠多型性心律失常,其中以缓慢性心律失常为主,并呈剂量依赖性。     

阿司咪唑对小鼠心脏的急性毒性研究

目的通过观察小鼠心电图的变化,研究阿司咪唑对心脏的急性毒性,了解其致心律失常的类型,推测其致心律失常的机制.方法用不同剂量的阿司咪唑对小鼠灌胃,分别记录不同时间的心电图变化.结果阿司咪唑使多数小鼠心率减慢,P-R间期和Q-T间期延长,随剂量增加,甚至可引起完全性房室传导阻滞和窦性停搏.少数情况也会出现窦性、室性心动过速等快速性心律失常.结论阿司咪唑可引起小鼠多型性心律失常,其中以缓慢性心律失常为主,并呈剂量依赖性.     

新药简报

<正> 扑痫酮的新用途 Q-T间期延长综合征(LQTS)的特征是Q-T间期延长,运动或情感激动易诱发室速、室颤并导致昏厥、猝死。过去治疗常用静注利多卡因、溴苄胺以消除室性快速心律失常,试用钾盐、钙盐、毛花丙甙或苯妥英钠以缩短Q-T间期,也有用β-阻断剂抑制情感兴奋或活动引起的交感兴奋,但疗效均不理想。     

槐定碱抗心律失常作用及其机理

槐定碱(Sop)明显对抗由乌头碱、BaCl_2、CaCl_2、肾上腺素和哇巴因诱发的心律失常,提高家兔左心室电致颤阈。Sop减慢大鼠和家兔的正常心率,延长P-R和校正Q-T间期;减慢离体家兔右心房自发频率。Sop使异丙肾上腺素加速离体心房自发频率的量效曲线右移并抑制最大反应。Sop 40μM使离体豚鼠心室乳头肌细胞动作电位零相去极化最大上升速率V_(max)明显减慢,有效不应期(ERP)和动作电信时程(APD)显著延长。提示Sop具有奎尼丁样作用,阻滞钠通道是其抗心律失常的主要作用机理。     

盐酸胺碘酮治疗急性心肌梗死后室性心律失常的临床效果研究

目的探讨盐酸胺碘酮治疗急性心肌梗死(AMI)后室性心律失常的临床效果。方法94例急性心肌梗死后室性心律失常患者,随机分为对照组和观察组,各47例。对照组使用盐酸利多卡因进行治疗,观察组使用盐酸胺碘酮进行治疗。对比两组患者的临床疗效、不良反应发生率及治疗前后室性心律失常发生次数及持续时间、心电图指标(QTc间期、QTd间期、PR间期、QRS波时限)变化。结果观察组治疗总有效率为93.62%,明显高于对照组的74.47%,差异有统计学意义(P<0.05)。治疗前,两组室性心律失常发生次数及持续时间比较差异无统计学意义(P>0.05);治疗后,观察组室性心律失常发生次数(892.8±100.4)次/24 h明显少于对照组的(1194.4±154.6)次/24h,持续时间(3.09±0.25)min/次明显短于对照组的(4.87±0.33)min/次,差异有统计学意义(P<0.05)。治疗前,两组QTc间期、QTd间期、PR间期、QRS波时限比较差异无统计学意义(P>0.05);治疗后,观察组QTc间期、QTd间期、PR间期明显长于对照组,QRS波时限明显短于对照组,差异有统计学意义(P<0.05)。观察组不良反应发生率明显低于对照组(P<0.05)。结论盐酸胺碘酮治疗急性心肌梗死后室性心律失常的临床效果显著,能有效抑制室性心律失常发病,改善心电图指标,且不良反应发生率低,具有积极的临床意义。     

Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat

The actions of intravenous verapamil against arrhythmias induced by occlusion of a coronary artery were investigated in conscious rats. Verapamil (2-20 mg kg-1, i.v. given pre-occlusion) dose-dependently reduced arrhythmias in rats with either large or small occluded zones at an ED50 of 6 mg kg-1. This dose was effective when given immediately post-occlusion. Severe arrhythmias, as opposed to PVC, were preferentially reduced. In conscious, and pentobarbitone-anaesthetized rats, verapamil (6 mg kg-1) had different effects on electrically-induced arrhythmias, and the ECG, from an equi-effective anti-arrhythmic dose of quinidine (20 mg kg-1, i.v.). Quinidine decreased following frequency, but increased threshold current and pulse width, whereas verapamil did not. Both drugs increased P-R interval, but only quinidine increased QRS and Q-T intervals. Thirty minutes post-occlusion, the verapamil content of tissue and blood was determined after a 6 mg kg-1 dose given pre- or post-occlusion. Measurable levels of verapamil were found in both normal and ischaemic myocardium. Plasma and plasma water concentrations were 3.6 +/- 0.8 mumol l-1 and 0.6 +/- 0.1 mumol l-1 (mean +/- s.e. mean), respectively following post-occlusion administration vs. 2.7 +/- 1.2 and 0.24 +/- 0.04 for pre-occlusion administration. Plasma water concentrations were close to IC50 values for inhibition of contractility in rat atria and ventricles. Similar concentrations depressed slow action potentials induced in rat ventricles by raised K+ We suggest that the ability of verapamil to prevent severe ventricular arrhythmias following myocardial ischaemia in the conscious rat is largely due to the calcium antagonist effects of the drug.     

Interactions between bufadienolides derived from toad venom and verapamil in langendorff-perfused guinea-pig hearts

Drug toxicity may occur due to dangerous drug combination. We aimed to investigate the influence of verapamil (a P-gp inhibitor) - bufadienolides interaction on cardiotoxicity and bufadienolide uptake by the isolated heart. The study was performed in Langendorff isolated perfused guinea-pig hearts by bufadienolides infusion in the absence and presence of verapamil (250, 500 ng/ml). Arrhythmia parameters were evaluated by ECG and the content of bufadienolides in heart were measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS). In the present of verapamil, the wide QRS duration and lightly rapid heart rate (HR) were markedly reduced in the early stage of bufadienolide intoxication. However, the ECG changes characterized by prolonged P–R interval, and slow heart rate and low QRS amplitude in the late stage of bufadienolide intoxication were significantly enhanced. Furthermore, the contents of a variety of bufadienolide compounds in the verapamil + bufadienolide group were significantly higher when cardiac arrest occurred. Although verapamil reduced the bufadienolide-induced ventricular arrhythmias, verapamil worsened heart block and lethal bradycardia of bufadienolides partly via increasing the uptake of bufadienolides in heart tissue, which could compromise the protective effects of verapamil against bufadienolide intoxication. These results suggested that the verapamil may produce dangerous interactions with drugs containing bufadienolides.     

Electrophysiological and antiarrhythmic actions of the kappa agonist PD 129290, and its R,R (+)-enantiomer, PD 129289.

1. The S,S (-)-enantiomer PD 129290, a kappa agonist, and its corresponding inactive R,R (+)-enantiomer (PD 129289) were studied in rat isolated hearts and in intact rats for cardiovascular and antiarrhythmic actions. The electrophysiological actions of PD 129290 were also studied in rat isolated cardiac myocytes using voltage clamp. 2. Ventricular pressure, heart rate and ECG were studied in isolated hearts while blood pressure, heart rate and ECG were studied in pentobarbitone-anaesthetized rats. In the latter, responses to electrical stimulation and coronary occlusion were also investigated. 3. In isolated hearts both enantiomers, over the concentration range 2-16 microM, dose-dependently reduced systolic ventricular pressure and heart rate while prolonging the P-R and QRS intervals of the ECG. 4. At doses of 1-32 mumol kg-1 both enantiomers reduced blood pressure and heart rate in anaesthetized rats. In addition, both enantiomers increased the size of the RSh and increased P-R, QRS, and Q-T intervals of the ECG. The thresholds for premature beats and ventricular fibrillation were dose-dependently increased by PD 129289. At lower doses PD 129290 decreased thresholds. These decreases were blocked by naloxone to reveal underlying increases similar to those seen with PD 129289. Both enantiomers increased refractory periods. 5. Naloxone (8 mumol kg-1) did not alter any of the actions of PD 129290, except to abolish the initial decreases in thresholds in intact rats seen with lower doses of PD 129290. 6. Both enantiomers (2 and 8 mumol kg-1) equally reduced arrhythmias in anaesthetized rats subject to occlusion of a coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactions of beta-adrenoceptor antagonists and thyroid hormones in the control of heart rate in the dog.

Propranolol, sotalol and nadolol have been infused into conscious dogs, and doses at which the three drugs are equipotent as beta-adrenoceptor antagonists determined. In euthyroid dogs, sotalol was more effective at lowering heart-rate than an equivalent dose of propranolol, while an equivalent dose of nadolol was without effect. Hyperthyroidism potentiated the lowering of heart-rate by sotalol, but inhibited that by propranolol. The effect of sotalol on heart-rate was correlated with its prolongation of the Q-T interval of the ECG. That of propranolol was correlated with its prolongation of the P-R interval. Nadolol did not affect P-R interval or Q-T interval except at relatively high dosage. We conclude that the tachycardia of hyperthyroidism is not affected by blockade of beta-adrenoceptors and therefore that it is not mediated by adrenergic mechanisms. The effectiveness of propranolol and sotalol in lowering heart-rate must be due to actions peculiar to those drugs, and not to beta-adrenoceptor antagonism.     

Electromechanical effects of bepridil on rabbit isolated hearts.

Electromechanical effects of a new antianginal agent, bepridil, on Langendorff-perfused rabbit hearts were compared with those of verapamil and lidocaine. Bepridil at concentrations above 2 X 10(-7)M caused a dose-related decrease in heart rate (HR), a prolongation of the atrio-His bundle conduction time (A-H interval) and a prolongation of the functional refractory period (FRP) of the atrioventricular (A-V) node. Similar changes in HR, A-H interval and the FRP of the A-V node were observed with verapamil at concentrations above 2 X 10(-8)M. Lidocaine at above 4 X 10(-5)M prolonged slightly the A-H interval and the FRP of the A-V node but did not decrease the HR. Bepridil at concentrations above 10(-6)M prolonged both the His bundle-ventricular conduction time (H-V interval) and the effective refractory period (ERP) of ventricular muscles. Similar changes in the H-V interval and in the ERP of ventricular muscles were observed with lidocaine at above 10(-5)M. Verapamil ranging between 5 X 10(-8)M and 8 X 10(-7)M had no effect on the H-V interval and appreciably shortened the ERP of ventricular muscles. Bepridil at concentrations above 2 X 10(-6)M reduced the developed tension as did verapamil at above 10(-7)M. On a molar basis, the depressant effect of bepridil on HR and the A-V nodal conduction, which may reflect inhibitory action on the slow channels, was less than one tenth that of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of PKC represses the prolongation of QRS complex in EAM rat model

OBJECTIVE To test the hypothesis,using experimental autoimmune myocarditis(EAM) rat model, that unexplained cases of malignant ventricular arrhythmias were caused by protein kinase C(PKC) activation. METHODS Using EAM rats model and isolated heart infusion technic, the effect of PKC on the QRS complex and molecular mechanism will be clarified. RESULTS In isolated hearts of normal rats, PKC agonist PMA induced prolongation of QRS complex. Mechanistically, activation of PKC increases phosphorylation and changes distribution of Cx43, and causes prolongation of QRS duration.In contrast, administration of PKC inhibitor with Ro-32-0432 in EAM rat after the most severe inflammation period still significantly al eviated the prolongation of QRS complex.CONCLUSION Pharmacological inhibition of PKC ameliorates the prolongation of QRS complex in EAM rat, provide a potential therapeutic strategy for arrhythmias induced by myocarditis.     

Correlation between verapamil plasma concentration and P-R prolongation in essential hypertension

Plasma verapamil concentration was correlated with serial electrocardiographic P-R intervals in patients with essential hypertension receiving immediate-release (80 to 120 mg three times a day) or sustained-release (240 mg daily) verapamil. The mean P-R interval in 22 patients taking placebo and immediate-release verapamil was 0.18 second. The borderline first-degree atrioventricular block of three patients did not change during treatment. Plasma verapamil concentrations of patients with a P-R interval longer than 0.20 second and of those with a P-R interval of 0.20 second or less were 169 +/- 73 ng/mL and 63 +/- 8 ng/mL, respectively. Six patients taking sustained-release verapamil had a maximal mean P-R interval of 0.19 +/- 0.01 second during 24-hour ambulatory electrocardiographic monitoring. P-R intervals were 0.22 second or more in two patients, but they returned to normal by hour 7 for one and by hour 20 for the other patient. In summary, transient P-R prolongation occurred with oral verapamil therapy, but no patient, regardless of baseline P-R interval, developed high-grade atrioventricular block.     

Experimental amitriptyline intoxication: electrophysiologic manifestations and management

Amitriptyline intoxication can result in severe ventricular arrhythmias that may be refractory to medical management. The mechanisms of these arrhythmias are unclear, and their optimal management is problematic. We studied the cardiac effects of amitriptyline infusion in anesthetized and awake dogs. Amitriptyline significantly increased heart rate, QRS duration, and AH and HV intervals. The concentration-response curves for these effects were, however, quite different, with significant changes beginning at a concentration of 1.5 +/- 0.4 mg/L for heart rate, compared with 2.4 +/- 0.4 mg/L for QRS and HV intervals and 3.7 +/- 0.5 mg/L for the AH interval. Ventricular tachyarrhythmias developed after marked QRS widening had occurred, and appeared in all six awake dogs and five of the six anesthetized dogs studied. Sodium bicarbonate was given to seven animals with ventricular tachyarrhythmias, and it rapidly reversed the arrhythmia in all instances. The benefit from sodium bicarbonate could not be attributed to changes in serum potassium or amitriptyline concentrations. It may have been due to alkalinization or changes in serum sodium concentration. These experiments suggest that: (a) amitriptyline intoxication frequently produces ventricular tachyarrhythmias, if high enough drug concentrations are achieved; (b) these arrhythmias are associated with marked slowing of intraventricular conduction; and (c) sodium bicarbonate is effective therapy for amitriptyline-induced ventricular arrhythmia.