抗心律失常药物对蟾酥致小鼠心律失常的影响

Effect of anti-arrhythmia drugs on mouse arrhythmia induced by Bufonis Venenum

比较苯妥英钠、利多卡因(钠通道阻滞药)、普萘洛尔(β肾上腺素受体拮抗药)、胺碘酮(延长动作电位时程药)和维拉帕米(钙通道阻滞药)对蟾酥诱导小鼠心律失常的抑制作用及对离体小鼠心脏的蟾酥致死量的影响。采用动态心电图记录蟾酥诱导小鼠心律失常。观察模型组和各给药组心电图的P-R间期、QRS时程、Q-T间期、T波幅度和HR的变化,统计各心律失常发生率、存活率及心律失常评分。采用离体小鼠心脏灌流,记录心脏的蟾酥致死量。与模型组相比,苯妥英钠组的QRS时程缩短且心率减慢;室性心律失常的发生率降低,存活率增高;显著增加离体小鼠心脏的蟾酥累积致死量。利多卡因组与模型组相比,P-R间期和QRS时程缩短;室性心律失常发生率降低;显著增加离体小鼠心脏的蟾酥累积致死量。普萘洛尔组与模型组相比,P-R间期、QRS时程和Q-T间期缩短;室上性及室性心律失常的发生率降低。胺碘酮显著减慢模型小鼠的心率并且降低模型小鼠室性心律失常的发生率。维拉帕米显著延长模型小鼠P-R间期,抑制Q-T间期延长;减少室上性及室性心律失常的发生;显著减少离体小鼠心脏的蟾酥累积致死量。整体动物实验中,苯妥英钠对蟾酥诱导小鼠的心律失常最有效,其次是利多卡因和普萘洛尔,胺碘酮作用不明显,维拉帕米在蟾酥致小鼠心律失常中需慎重使用。结果提示,蟾酥诱导小鼠的室性心律失常可能与钠离子通道关系密切,室上性心律失常可能与β肾上腺素受体关系密切,传导阻滞可能与钙通道关系密切。离体实验中,苯妥英钠对模型小鼠离体心脏的直接保护最有效,其次是利多卡因,普萘洛尔和胺碘酮没有明显作用,维拉帕米减少蟾酥累积致死量。

This study is to investigate the effects of phenytoin sodium,lidocaine（sodium channel block-ers）,propranolol（β-adrenergic receptor antagonist）,amiodarone（drugs prolonging the action potential duration） and verapamil（calcium channel blockers） on arrhythmia of mice induced by Bufonis Venenum（Chansu） and isolated mouse hearts lethal dose of Chansu.Arrhythmia of mice were induced by Chansu and then electrocardiograms（ECGs） were recorded.The changes of P-R interval,QRS complex,Q-T interval,T wave amplitude,heart rate（HR） were observed.Moreover,arrhythmia rate,survival rate and arrhythmia score were counted.Isolated mouse hearts were prefused,and the lethal dose of Chansu was recorded.Compared with control group,after pretreatment with phenytoin sodium,broadening of QRS complex and HR were inhibited,and the incidence of ventricular arrhythmia was reduced dramatically,while survival rate was improved;the isolated mouse hearts lethal dose of Chansu was increased significantly.After pretreatment with lidocaine,the prolongation of P-R interval and broadening of QRS complex were inhibited,and the incidences of ventricular arrhythmia were reduced dramatically,while survival rate was improved;the isolated mouse hearts lethal dose of Chansu was increased significantly.After pretreatment with propranolol,prolongation of P-R interval,broadening of QRS complex,prolongation of Q-T interval and HR were inhibited,and the incidences of both supraventricular and ventricular arrhythmias were reduced dramatically,while survival rate was improved.After pretreatment with amiodarone,HR was inhibited,the incidences of ventricular tachycardia were reduced dramatically.Lastly,after pretreatment with verapamil,the prolongation of P-R interval and Q-T interval were inhibited and the incidences of both supraventricular and ventricular arrhythmias were reduced dramatically;the isolated mouse hearts lethal dose of Chansu was reduced significantly.In in vivo experiments,phenytoin sodium was most effective against the mice arrhythmias induced by Chansu while cautious use of verapamil for Chansu inducing arrhythmia should be noted.It is also concluded that mice ventricular arrhythmias induced by Chansu might be most closely related to sodium channel,supraventricular arrhythmias might be related to β-adrenergic receptor,and calcium channel plays an important role in conduction block.In in vitro experiments,phenytoin sodium was most effective,followed by lidocaine and propranolol,and amiodarone had no obvious effect and verapamil reduced the lethal dose of Chansu.