Pereira Paula Juliana Seadi, Pugsley Michael K, Troncy Eric, Tan Wendy, Pouliot Mylene, Harper Claudia, Prefontaine Annick, Easter Alison, Wallis Rob, Miraucourt Lois, Huang Hai, Accardi Michael V, Boulay Emmanuel, Maghezzi Mohamed Said, Authier Simon
Citoxlab, Laval, QC, Canada.
Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC, Canada.
J Pharmacol Toxicol Methods. 2019 Sep-Oct;99:106589. doi: 10.1016/j.vascn.2019.106589. Epub 2019 May 31.
Spontaneous arrhythmia characterization in healthy rats can support interpretation when studying novel therapies. Male (n = 55) and female (n = 40) Sprague-Dawley rats with telemetry transmitters for a derivation II ECG. Arrhythmias were assessed from continuous ECG monitoring over a period of 24-48 h, and data analyzed using an automated detection algorithm with 100% manual over-read. While a total of 1825 spontaneous ventricular premature beats (VPB) were identified, only 7 rats (or 7.4%) did not present with any over the recording period. Spontaneous episode(s) of ventricular tachycardia (VT) were noted in males (27%) and females (3%). The incidence of VPB was significantly higher (p < 0.01) during the night time (7 pm-7 am) compared to daytime, while males presented with significantly (p < 0.001) more VPB than females. Most VPB were observed as single ectopic beats, followed by salvos (2 or 3 consecutive VPBs), and VT (i.e. 4 consecutive VPBs). Most VPBs were single premature ventricular contractions (PVCs) (57%), while the remaining were escape complexes (43%). Spontaneous premature junctional complexes (PJC) were also observed and were significantly more frequent during the night, and in males. Lastly, 596 episodes of spontaneous 2nd-degree atrioventricular (AV) block were identified and were significantly more frequent during the day time in males. Most 2nd-degree AV block episodes were Mobitz type I (57%), with a significantly (p < 0.05) higher incidence in males. This work emphasizes the importance of obtaining sufficient baseline data when undertaking arrhythmia analysis in safety study and provides a better understanding of both sex- and time- dependent effects of spontaneous arrhythmias in rats.
在研究新型疗法时，对健康大鼠的自发性心律失常特征进行分析有助于阐释相关结果。将遥测发射器植入55只雄性和40只雌性Sprague-Dawley大鼠体内，用于记录II导联心电图。通过连续24至48小时的心电图监测评估心律失常情况，并使用自动检测算法进行数据分析，同时进行100%的人工复查。共识别出1825次自发性室性早搏（VPB），只有7只大鼠（占7.4%）在记录期内未出现任何室性早搏。在雄性大鼠（27%）和雌性大鼠（3%）中均观察到自发性室性心动过速（VT）发作。与白天相比，夜间（晚上7点至早上7点）VPB的发生率显著更高（p<0.01），且雄性大鼠的VPB明显多于雌性大鼠（p<0.001）。大多数VPB表现为单个异位搏动，其次是连发（2或3个连续的VPB）和VT（即4个连续的VPB）。大多数VPB为单个室性早搏（PVC）（57%），其余为逸搏复合波（43%）。还观察到自发性交界性早搏（PJC），且在夜间和雄性大鼠中更为频繁。最后，共识别出596次自发性二度房室（AV）阻滞发作，在白天，雄性大鼠中的发作频率显著更高。大多数二度AV阻滞发作属于莫氏I型（57%），在雄性大鼠中的发生率显著更高（p<0.05）。这项工作强调了在安全性研究中进行心律失常分析时获取足够基线数据的重要性，并有助于更好地理解大鼠自发性心律失常的性别和时间依赖性效应。
