A Retrospective Comparison of Electrocardiographic Parameters in Ketamine and Tiletamine-Zolazepam Anesthetized Indian Rhesus Monkeys (Macaca mulatta).

IF 1.2 4区医学 Q4 PHARMACOLOGY & PHARMACY

International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-12-18 DOI:10.1177/10915818231221276

Laxit K Bhatt, Chitrang R Shah, Shital D Patel, Sudhir R Patel, Vipul A Patel, Rajesh J Patel, Nikita M Joshi, Niraj A Shah, Jitendra H Patel, Pankaj Dwivedi, Rajesh Sundar, Mukul R Jain

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Abstract

Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies.

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氯胺酮和利他敏-唑拉西泮麻醉印度恒河猴心电图参数的回顾性比较

在进入临床试验之前，先对恒河猴进行心电图评估，以确定候选分子的心血管安全性。这些动物通常通过氯胺酮（KTM）和瓦他敏-唑拉西泮（TZ）进行化学固定，以获得稳态心率并确保足够的人体安全性。本研究旨在评估这些麻醉方案对不同心电图参数的影响。与 TZ 麻醉组相比，KTM 麻醉组的心率明显降低，P 波持续时间、RR、QRS 和 QT 间期明显延长。PR 间期和 P 波振幅没有明显变化。在 TZ 和 KTM 麻醉组的雄性和雌性动物中观察到了这些参数的性别差异。对四种 QTc 公式在 TZ 麻醉恒河猴中的回归分析表明，QTcNAK（Nakayama）比 QTcHAS（Hassimoto）、QTcBZT（Bazett）和 QTcFRD（Fridericia）公式能更好地校正 QT 间期。QTcNAK 与 RR 间期的相关性最小（斜率最接近零，r = 0.01），在雌雄动物之间没有统计学意义。这些数据将有助于在非临床安全性评估研究中选择对猕猴进行化学约束的麻醉方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Toxicology 医学-毒理学

CiteScore

3.40

自引率

4.50%

发文量

审稿时长

4.5 months

期刊介绍： The International Journal of Toxicology publishes timely, peer-reviewed papers on current topics important to toxicologists. Six bi-monthly issues cover a wide range of topics, including contemporary issues in toxicology, safety assessments, novel approaches to toxicological testing, mechanisms of toxicity, biomarkers, and risk assessment. The Journal also publishes invited reviews on contemporary topics, and features articles based on symposia. In addition, supplemental issues are routinely published on various special topics, including three supplements devoted to contributions from the Cosmetic Review Expert Panel.