Weinhouse E, Kaplanski J, Jarenwattananon M, Nudel D B
Medical College of Wisconsin, Department of Pediatrics, Milwaukee.
Methods Find Exp Clin Pharmacol. 1989 Jun;11(6):367-72.
We have previously described a method for inducing atrial ectopic tachycardia (AET) in the anesthetized adult rat using digoxin, 30 mg/kg s.c. In this study, we used this model to study digoxin-verapamil interactions in young and older male rats and have found age-related differences in their responses to digoxin alone and to digoxin-verapamil interactions as well. Overall, 90% of the animals of both groups combined that developed AET, developed a ventricular proarrhythmic response to verapamil. Thus, this model might broaden the pre-clinical evaluation of anti-arrhythmic agents and predict which drugs are most likely to have a proarrhythmic effect.
我们之前曾描述过一种在麻醉的成年大鼠中使用地高辛(30毫克/千克皮下注射)诱发房性异位性心动过速(AET)的方法。在本研究中,我们使用该模型研究年轻和老年雄性大鼠体内地高辛与维拉帕米的相互作用,并且发现它们对单独使用地高辛以及地高辛与维拉帕米相互作用的反应存在年龄相关差异。总体而言,两组中出现AET的动物合并起来有90%对维拉帕米产生了室性促心律失常反应。因此,该模型可能会拓宽抗心律失常药物的临床前评估范围,并预测哪些药物最有可能产生促心律失常作用。