Measurement of the inducing rate of arrhythmia
Programmed electrical stimulation (S1S2S3) and burst pacing (S1S1) were used sequentially to induce arrhythmia at baseline, after drug administration, or during LL-ES of ARVGP. Atrial arrhythmia was provoked first by S1S2S3at the base of the left atrial appendage, and ventricular arrhythmia was induced at the left ventricular via bipolar screw-in pacing with leads fixed epicardially[8]. Each two-burst pacing protocol was performed with a 10 min interval in-between to allow for recovery from the rapid pacing to occur via atrial remodeling. The programmed stimulation protocol was set at basic cycle lengths of 400 and 300 ms with up to two extra stimuli (S3). All stimuli were monitored on a 64-channel electrophysiological recorder (Henan Huanan Medical Science & Technology Co., Zhengzhou, China). The first extra stimulus (S2) was introduced with an S1-S2 interval 30 ms longer than the atrial effective refractory period, and the coupling interval was shortened in 10 ms decrements. If the S1-S2 extra stimuli failed to induce arrhythmia, a second extra stimulus (S3) was introduced at 10 ms scanning decrements during an S1-S2 interval set at 80% of the basic cycle length. If programmed stimulation failed to induce arrhythmia, burst pacing at a cycle length of 200 ms for 30 seconds was applied to provoke arrhythmia, and the cycle length was subsequently decreased to 160 and 120 ms if 200 ms was ineffective. The above electrical stimulation procedure was repeated twice. A successful endpoint was defined as arrhythmia started either by S1S2S3, by a subsequent S1S1, or both if either procedure failed. Arrhythmiais defined as atrial or ventricular tachycardia (sustained>10sec), atrial fibrillation (sustained>30sec), or ventricular flutter or fibrillation. If malignant arrhythmia occurred (persistent ventricular tachycardia over 5 min or ventricular flutter or fibrillation), epicardial electrical conversion (50J) was performed immediately to recover a stable internal environment.

Measurement of VERP, stroke volume of the LV, and ejection fraction of the LV

VERP was measured at baseline and after treatment with a placebo, drugs, and LL-ES, respectively. It was recorded using the extra stimulus technique (basic cycle length of 400 ms and final extra stimulus steps of 5 ms; Electrophysiological Recorder, 64 channels, Henan Huanan Medical Science & Technology Co., Zhengzhou, China). Furthermore,transthoracic echocardiography was performed with dogs in the left lateral decubitus position, breathing slowly, using aphased-array probe(Vivid E9, GE, USA). The LV endocardial surface was detected using the Simpson′s method from the apical four-chamber view and the apical right heart two-chamber view to measure LVEDV and LVESV. Then, LVSV and LVEF were obtained at baseline and after 1 week of treatment with a placebo, drug, and LL-ES, respectively.