Kijtawornrat Anusak, Panyasing Yaowalak, Del Rio Carlos, Hamlin Robert L
QTest Labs, LLC., 6438 Fiesta Dr, Columbus, OH 43235, USA.
J Pharmacol Toxicol Methods. 2010 May-Jun;61(3):231-7. doi: 10.1016/j.vascn.2010.02.001. Epub 2010 Feb 12.
The short QT syndrome (SQTS) is characterized by a short QT interval resulting from accelerated ventricular repolarization, and may be associated with ventricular fibrillation but not torsades de pointes. There are abundant data on the adverse effects of long QT, but knowledge of SQTS is sparse. The aim of this study was to examine whether analyses of several ECG biomarkers (QT, QTcB, QTcF, QTcV, QT(btb), and QT(RR1000)) and dynamic restitution of the beat-to-beat QT-TQ relationship (TQ(min), %QT/TQ ratio>1, QT/TQ ratio(max)) can be used to assess ECG changes in conscious dogs.
Sling-trained dogs were infused with escalating concentration of levcromakalim (0, 1.0, 3.3, and 10.0 microg/kg/min), pinacidil (0, 3.3, 10.0, and 33.3 microg/kg/min), and nicorandil (0, 0.03, 0.1, and 0.3 mg/kg/min), drugs known to shorten QT. The RR, QT, QTcB, QTcF, QTcV, QT(RR1000), and TQ were measured before and after each concentration of the QT shortening test compounds.
Levcromakalim, pinacidil, and nicorandil but not vehicle significantly shortened RR, QT, QT(btb), QT(RR1000), and TQ but not QTc(B,F,V). The QT-RR cloud also shifted to the lower bounds of the normal QT-RR boundary by the test compounds. The percentage of beats with a QT/TQ ratio>1 was significantly increased in a dose response manner with levcromakalim and pinacidil and the lower TQ interval boundary (5th percentile) was decreased when compared to baseline or vehicle.
QT(btb), QT(RR1000), and dynamic beat-to-beat measurements of restitution constitute clinically applicable ECG biomarkers for assessment of changes associated with arrhythmogenic risk of ventricular fibrillation due to QT abbreviation.
短QT综合征（SQTS）的特征是由于心室复极加速导致QT间期缩短，可能与室颤相关，但与尖端扭转型室速无关。关于长QT的不良反应有大量数据，但对短QT综合征的了解却很少。本研究的目的是检验对几种心电图生物标志物（QT、QTcB、QTcF、QTcV、QT(btb)和QT(RR1000)）以及逐搏QT-TQ关系的动态恢复（TQ(min)、%QT/TQ比值>1、QT/TQ比值(max)）的分析是否可用于评估清醒犬的心电图变化。
对经吊带训练的犬输注浓度递增的左卡尼汀（0、1.0、3.3和10.0微克/千克/分钟）、匹那地尔（0、3.3、10.0和33.3微克/千克/分钟）和尼可地尔（0、0.03、0.1和0.3毫克/千克/分钟），这些药物已知可缩短QT。在每种浓度的QT缩短测试化合物给药前后测量RR、QT、QTcB、QTcF、QTcV、QT(RR1000)和TQ。
左卡尼汀、匹那地尔和尼可地尔而非赋形剂显著缩短RR、QT、QT(btb)、QT(RR1000)和TQ，但不缩短QTc(B,F,V)。测试化合物还使QT-RR云移至正常QT-RR边界的下限。与基线或赋形剂相比，左卡尼汀和匹那地尔使QT/TQ比值>1的搏动百分比呈剂量反应性显著增加，且较低的TQ间期边界（第5百分位数）降低。
QT(btb)、QT(RR1000)以及逐搏恢复的动态测量构成了临床上适用的心电图生物标志物，用于评估因QT缩短导致的室颤致心律失常风险相关的变化。
