双苯氟嗪对实验性心律失常及心室肌细胞内钙浓度的影响(英文)  

Effects of dipfluzine on experimental arrhythmias and cytosolic calcium concentration

作　　者：苗庆峰[1] 苏素文[1] 张伟[1] 郭鸣放[1] 李林芳[1] 孟静[1] 张永健[1] 

机构地区：[1]河北医科大学药理学教研室,河北石家庄050017

出　　处：《中国药理学与毒理学杂志》2006年第6期448-454,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家高技术研究发展计划(863)资助项目(2002AA2Z3132)~~

摘　　要：目的观察双苯氟嗪对实验性心律失常的作用及其可能机制。方法采用静脉灌流毒毛花苷G诱发豚鼠心律失常,心肌缺血再灌注诱发大鼠心律失常,观察双苯氟嗪的抗心律失常作用;利用激光共聚焦扫描显微镜观察双苯氟嗪对心室肌细胞内游离钙子浓度([Ca2 +]i)的影响。结果双苯氟嗪20mg·kg-1能提高毒毛花苷G诱发豚鼠室性早搏、室速、室颤和死亡的剂量;10 mg·kg-1提高诱发室性早搏的剂量。双苯氟嗪20 mg·kg-1减少心肌缺血再灌注诱发的大鼠室速、室颤发生率及动物死亡率;10mg·kg-1减少室颤发生率及动物死亡率。双苯氟嗪预先给药可降低豚鼠正常心室肌细胞[Ca2 +]i,并抑制细胞外高钙诱发的细胞[Ca2 +]i升高;在细胞外高钙已诱发细胞[Ca2 +]i升高的条件下,仍可降低[Ca2 +]i升高的程度。结论双苯氟嗪具有抗实验性心律失常作用,这种作用可能与其保持细胞内钙稳态有关。AIM To investigate whether dipfluzine （Dip） possesses antiarrhythmic effect on experimental arrhythmias and effect on cytosolic calcium in ventricular myocytes of guinea-pig. METHODS Experimental arrhythmias were induced by strophanthin G infusion through jugular vein in guinea-pigs and by myocardial ischemia-reperfusion （I-R） in rats respectively. Cytosolic calcium concentration （ [Ca^2＋]i ） of isolated guinea-pig ventricular myocytes was examined with laser confocal scanning microscope. RESULTS In guinea-pigs pretreatment with Dip 20 mg· kg^-1 increased the dosages of strophanthin G required to induce ventricular premature contraction （VP） , ventricular tachycardia （VT）, ventricular fibrillation （VF） and cardiac arrest （CA） , pretreatment with Dip 10 mg·kg^-1 increased the dosages of strophanthin G required to induce VP. In the I-R-induced arrhythmic model of rats, Dip 20mg·kg^- 1 decreased the number of rats exhibiting VT, VF and CA, and the number of rats exhibiting VF and CA was decreased by Dip 10 mg·kg^-1. Both Dip and verapamil （Ver） decreased [Ca^2＋]iof the ventricular myocytes in normal Tyrode＇s solution. The Ca^2＋ overload evoked by high extracellular Ca^2＋ levels was inhibited by Dip and Vet, and the prophylactic effect of Dip was less than that of Ver, while the curative effect of Dip was more obvious than that of Ver. CONCLUSION Dip has antiarrhythmic effect, which is likely related to the modulation on the intracellular calcium homeostasis.

关 键 词：抗心律失常药 双苯氟嗪 心律失常 心肌钙 细胞内 

分 类 号：R96[医药卫生—药理学]