The incidence of spontaneous arrhythmias in telemetered beagle dogs, Göttingen Minipigs and Cynomolgus non-human primates: A HESI consortium retrospective analysis

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Emmanuel Boulay , Loïs S. Miraucourt , Michael K. Pugsley , Matthew M. Abernathy , Ray Chui , Jill Dalton , Marjorie Demers , Noel Dybdal , Elissa Gazaille , Andrea Greiter-Wilke , Peter Hoffmann , Hai Huang , Carrie LaDuke , Kevin Norton , Jennifer B. Pierson , Isabelle Reeves , Brian Roche , Eric I. Rossman , Albert E. Schultze , Hai-Ming Tang , Simon Authier
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引用次数: 1

Abstract

Introduction

Characterization of the incidence of spontaneous arrhythmias to identify possible drug-related effects is often an important part of the analysis in safety pharmacology studies using telemetry.

Methods

A retrospective analysis in non-clinical species with and without telemetry transmitters was conducted. Electrocardiograms (24 h) from male and female beagle dogs (n = 131), Göttingen minipigs (n = 108) and cynomolgus non-human primates (NHP; n = 78) were analyzed.

Results

Ventricular tachycardia (VT) was observed in 3% of the dogs but was absent in minipigs and NHPs. Ventricular fibrillation (VF) was not observed in the 3 species. Ventricular premature beats (VPBs) were more frequent during daytime and atrioventricular blocks (AVBs) were more frequent at night in all species. A limited number of animals exhibited a high arrhythmia frequency and there was no correlation between animals with higher frequency of an arrhythmia type and the frequency of other arrythmias in the same animals. Clinical chemistry or hematology parameters were not different with or without telemetry devices. NHP with a transmural left ventricular pressure (LVP) catheter exhibited a greater incidence of VPBs and PJCs compared to telemetry animals without LVP.

Discussion

All species were similar with regards to the frequency of ventricular ectopic beats (26–46%) while the dog seemed to have more frequent junctional complexes and AVB compared to NHP and minipigs. Arrhythmia screening may be considered during pre-study evaluations, to exclude animals with abnormally high arrhythmia incidence.

遥测比格犬、哥廷根迷你猪和食蟹猴非人类灵长类动物自发性心律失常的发生率:HESI联盟回顾性分析
引言在使用遥测的安全药理学研究中,表征自发性心律失常的发生率以确定可能的药物相关影响通常是分析的重要组成部分。方法对使用和不使用遥测发射器的非临床物种进行回顾性分析。分析了雄性和雌性比格犬(n=131)、哥廷根小型猪(n=108)和食蟹猴非人类灵长类动物(NHP;n=78)的心电图(24小时)。结果3%的犬出现室性心动过速(VT),但在小型猪和NHP中没有。在3个物种中未观察到心室颤动(VF)。在所有物种中,室性早搏(VPB)在白天更频繁,房室传导阻滞(AVB)在夜间更频繁。数量有限的动物表现出高心律失常频率,心律失常类型频率较高的动物与同一动物中其他心律失常的频率之间没有相关性。无论有无遥测装置,临床化学或血液学参数均无差异。与没有LVP的遥测动物相比,具有透壁左心室压(LVP)导管的NHP表现出更大的VPB和PJC发生率。讨论所有物种的心室异位搏动频率相似(26-46%),而与NHP和小型猪相比,狗似乎有更频繁的交界复合体和AVB。研究前评估期间可考虑进行心律失常筛查,以排除心律失常发生率异常高的动物。
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来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
期刊介绍: Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.
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