Weigand Kyle, Witte Russell, Moukabary Talal, Chinyere Ike, Lancaster Jordan, Pierce Mary Kaye, Goldman Steven, Juneman Elizabeth
IEEE Trans Biomed Eng. 2017 Jun;64(6):1393-1399. doi: 10.1109/TBME.2016.2605578. Epub 2016 Sep 2.
The objective of this study was to define the clinical relevance of in vivo electrophysiologic (EP) studies in a rat model of chronic ischemic heart failure (CHF).
Electrical activation sequences, voltage amplitudes, and monophasic action potentials (MAPs) were recorded from adult male Sprague-Dawley rats six weeks after left coronary artery ligation. Programmed electrical stimulation (PES) sequences were developed to induce sustained ventricular tachycardia (VT). The inducibility of sustained VT was defined by PES and the recorded tissue MAPs.
Rats in CHF were defined ( 0.05) by elevated left ventricular (LV) end-diastolic pressure (5 ± 1 versus 18 ± 2 mmHg), decreased LV + d P/dt (7496 ± 225 versus 5502 [Formula: see text] s), LV - dP/dt (7723 ± 208 versus 3819 [Formula: see text]), LV ejection fraction (79 ± 3 versus [Formula: see text]), peak developed pressure (176 ± 4 versus 145 ± 9 mmHg), and prolonged time constant of LV relaxation Tau (18 ± 1 versus 29 ± 2 ms). The EP data showed decreased ( 0.05) electrogram amplitude in border and infarct zones (Healthy zone (H): 8.7 ± 2.1 mV, Border zone (B): 5.3 ± 1.6 mV, and Infarct zone (I): 2.3 ± 1.2 mV), decreased MAP amplitude in the border zone (H: [Formula: see text] 1.0 mV, B: 9.7 ± 0.5 mV), and increased repolarization heterogeneity in the border zone (H: 8.1 ± 1.5 ms, B: 20.2 ± 3.1 ms). With PES we induced sustained VT (>15 consecutive PVCs) in rats with CHF (10/14) versus Sham (0/8).
These EP studies establish a clinically relevant protocol for studying genesis of VT in CHF.
The in vivo rat model of CHF combined with EP analysis could be used to determine the arrhythmogenic potential of new treatments for CHF.
本研究的目的是确定在慢性缺血性心力衰竭（CHF）大鼠模型中体内电生理（EP）研究的临床相关性。
在成年雄性Sprague-Dawley大鼠左冠状动脉结扎六周后，记录其电激活序列、电压幅度和单相动作电位（MAPs）。制定程序电刺激（PES）序列以诱发持续性室性心动过速（VT）。持续性VT的诱发性由PES和记录的组织MAPs确定。
CHF大鼠的定义为（P<0.05）左心室（LV）舒张末期压力升高（5±1对18±2 mmHg）、LV + dP/dt降低（7496±225对5502 [公式：见正文] s）、LV - dP/dt降低（7723±208对3819 [公式：见正文]）、LV射血分数降低（79±3对[公式：见正文]）、峰值收缩压降低（176±4对145±9 mmHg）以及LV舒张时间常数Tau延长（18±1对29±2 ms）。EP数据显示边界区和梗死区的心电图幅度降低（P<0.05）（健康区（H）：8.7±2.1 mV，边界区（B）：5.3±1.6 mV，梗死区（I）：2.3±1.2 mV），边界区的MAP幅度降低（H：[公式：见正文] 1.0 mV，B：9.7±0.5 mV），并且边界区的复极异质性增加（H：8.1±1.5 ms，B：20.2±3.1 ms）。通过PES，我们在CHF大鼠（10/14）中诱发出持续性VT（>15个连续室性早搏），而假手术组大鼠（0/8）未诱发。
这些EP研究建立了一个用于研究CHF中VT发生机制的临床相关方案。
CHF大鼠体内模型与EP分析相结合可用于确定CHF新治疗方法的致心律失常潜力。
