Reference intervals and method sensitivity for electrocardiology, hemodynamics, and body temperature parameters in healthy cynomolgus monkeys

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Xiefan Fang, Stephen D. Tichenor
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引用次数: 1

Abstract

In nonclinical studies, electrocardiograms (ECG) of cynomolgus monkey are recorded intermittently by external leads in manually restrained animals (snapshot recording) or continuously by jacketed external telemetry (JET) or implanted radiotelemetry transmitter in freely moving animals. With the implanted device, blood pressure and core body temperature can be monitored simultaneously. Despite the frequent use of cynomolgus monkeys in nonclinical safety pharmacology testing, few reference data are available for this species, comparisons of the ECG recording methods are limited, and power analyses are seldom conducted. In this study, pretreatment data were recorded from 406, 663, and 131 healthy experimentally naïve monkeys using the snapshot, JET, and implantable method, respectively, from 2019 to 2021. Reference intervals were determined for ECG, blood pressure, and body temperature parameters. Diurnal effects were observed in these parameters, with the exception of QRS and pulse pressure. The QRS, QT, and heart rate-corrected QTc intervals, as well as blood pressure, had a weak positive relationship with age and/or body weight. There were no sex differences in these parameters, and the country of origin only had minimal influences. Compared to telemetry, snapshot ECG data had shorter RR, PR, and QT intervals and longer QRS interval. The JET and implanted telemetry ECG data were comparable. Effect size analysis was conducted to estimate the method sensitivity for each parameter in common non-clinical study design scenarios. Snapshot recording, JET, and implanted telemetry were sensitive to detect 7–15 milliseconds of changes in QTc intervals in standard study designs, indicating these are powerful methods for assessment of QT prolongation in vivo.

健康食蟹猴心电学、血流动力学和体温参数的参考区间和方法敏感性
在非临床研究中,食蟹猴的心电图(ECG)在人工约束的动物中通过外部引线间歇记录(快照记录),或在自由运动的动物中通过夹套外部遥测(JET)或植入无线电遥测发射机连续记录。通过植入装置,可以同时监测血压和核心体温。尽管食蟹猴经常用于非临床安全性药理学试验,但该物种的参考资料很少,心电图记录方法的比较有限,功率分析也很少进行。在本研究中,分别使用快照、JET和植入方法记录了2019年至2021年406、663和131只健康实验猴子naïve的预处理数据。确定心电图、血压和体温参数的参考区间。除QRS和脉压外,这些参数均观察到日效应。QRS、QT、心率校正QTc间隔以及血压与年龄和/或体重呈弱正相关。这些参数没有性别差异,原籍国的影响也很小。与遥测相比,快照心电图的RR、PR、QT间期较短,QRS间期较长。JET和植入式遥测心电图数据具有可比性。进行效应量分析,以估计方法对常见非临床研究设计方案中每个参数的敏感性。在标准的研究设计中,快照记录、JET和植入遥测技术可以灵敏地检测到7-15毫秒的QTc间隔变化,这表明这些方法是评估体内QT延长的有效方法。
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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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