QT and RR intervals in conscious and anesthetized guinea pigs with highly varying RR intervals and given QTc-lengthening test articles
QT and RR intervals in conscious and anesthetized guinea pigs with highly varying RR intervals and given QTc-lengthening test articles
复制标题
DOI：
10.1093/toxsci/kfg254
复制
发表时间：
2003-12-01
影响因子：
3.8
通讯作者：
Hamlin, DM
中科院分区：
文献类型：
--
作者：
Hamlin, RL;Kijtawornrat, A;Hamlin, DM
使用一种用于获得清醒动物心电图的简易系统，对12只清醒和麻醉动物、4只给予溶媒（0.5%甲基纤维素）和QT延长供试品的清醒动物以及6只给予认为不会延长QTc的供试品的动物进行研究。在通过双极经胸ECG监测ECG的12只动物中，当它们在吊带中清醒时以及在用氯胺酮/甲苯噻嗪麻醉后，用1.0 mg/kg扎替雷定减慢心率。QT与RR的回归方程为：清醒动物QT = 44.7，RR = 132.9，r（2）= 0.7; QT = 79.4在RR - 287.4中，麻醉动物的r（2）= 0.8，RR间期在150和550 ms之间变化。麻醉剂在所有RR间期均增加QT（p < 0.001），但与清醒豚鼠相比，不改变QT和RR之间关系的斜率。Fridericia法最适合清醒豚鼠RR间期QT校正，而Bazett法最适合麻醉动物校正。经口给予西沙必利、酮康唑和索他洛尔（阳性供试品）的所有清醒豚鼠的QTc均显著延长，甲基纤维素（溶媒）或普萘洛尔、维拉帕米或依那普利（阴性对照）均未发生变化。这些技术和关系表明，这种方法可能是有用的，在探索新的药理学实体的致扭转性室性心动过速的影响。
A facile system for obtaining electrocardiograms from conscious animals was used to conduct studies on 12 animals studied both conscious and anesthetized, on 4 conscious animals given vehicle (0.5% methylcellulose) and QT-lengthening test articles, and on 6 animals given test articles thought to not lengthen QTc. In 12 animals whose ECGs were monitored via a bipolar transthoracic ECG, heart rates were slowed with 1.0 mg/kg zatebradine, while they were conscious in their slings, and after being anesthetized with ketamine/xylazine. The following regression equations were obtained relating QT to RR: QT = 44.7 In RR - 132.9, r(2) = 0.7, for conscious animals; QT = 79.4 In RR - 287.4, r(2) = 0.8 for anesthetized animals, with RR intervals varying between 150 and 550 ms. The anesthetic increases QT at all RR intervals (p < 0.001), but does not change the slope of the relationship between QT and RR when compared with the conscious guinea pig. The Fridericia method was best for correcting QT for RR interval in conscious guinea pigs, but the Bazett method was best for correcting in anesthetized animals. QTc lengthened significantly in all conscious guinea pigs given, orally, cisapride, ketoconazole, and sotalol (positive test articles) and did not change with methylcellulose (the vehicle) or with propranolol, verapamil, or enalapril (negative controls). These techniques and relationships demonstrate that this methodology may be useful in exploring torsadogenic effects of novel pharmacological entities.