Comparison of different QT correction methods for nonclinical safety assessment in ketamine-anesthetized Indian rhesus monkeys (<i>Macaca mulatta</i>)

Bhatt, Laxit; Shah, Chitrang; Patel, Rajesh; Patel, Shital D.; Patel, Sudhir R.; Patel, Vipul; Patel, Jitendra; Dwivedi, Pankaj; Shah, Niraj; Sundar, Rajesh; Jain, Mukul

doi:10.1080/15376516.2023.2187730

Cited by 1 publication

(10 citation statements)

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“…This trend of QT correction observed in TZ-anaesthetized monkeys was similar to the data observed in our previous study on KTM-anaesthetized Indian rhesus monkeys (Table 5). 28 Sex-based significance was not observed in any of the QTc formulas tested in this study in TZ-anaesthetized monkeys.…”

Section: Resultsmentioning

confidence: 57%

“…The nomenclature of these formulas is based on the technique previously published by us. 28 Each formula has been provided with the initials 'QTc' standing for "corrected QT interval", followed by the first author's name's first letter and two characters relevant to the author's name in upper case. QTc formulas used in this study are listed in Table 2.…”

Section: Ecg Datamentioning

confidence: 99%

“…The corrected QT interval finds extensive application in pharmaceutical and clinical research. 28,[43][44][45] In the current study, we have examined the QT correction in TZ-anesthetized rhesus monkeys. In our previously conducted study on KTManesthetized rhesus monkeys, we have extensively evaluated these QTc formulas for their use in NHP toxicology studies.…”

Section: Qt Interval Correction and Qt-heart Rate Independencementioning

confidence: 99%

“…These similarities make rhesus monkeys an important and relevant animal model for understanding the effects of test molecules on the human heart. 6,10,[25][26][27][28] To obtain a steady-state heart rate in rhesus monkeys and to minimize harm to animals or personnel while handling conscious animals, electrocardiographic examination can be performed in rhesus monkeys under anesthesia. 28,29 Ketamine (KTM) and tiletamine-zolazepam (TZ) are two of the most commonly used anesthetics in NHPs.…”

Section: Introductionmentioning

confidence: 99%

“…6,10,[25][26][27][28] To obtain a steady-state heart rate in rhesus monkeys and to minimize harm to animals or personnel while handling conscious animals, electrocardiographic examination can be performed in rhesus monkeys under anesthesia. 28,29 Ketamine (KTM) and tiletamine-zolazepam (TZ) are two of the most commonly used anesthetics in NHPs. These agents induce short-term anesthesia required for performing various experimental procedures such as physical examination, ophthalmic examination, and hemodynamic parameters monitoring.…”

Section: Introductionmentioning

confidence: 99%

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

Bhatt,

Shah,

Patel

et al. 2023

Int J Toxicol

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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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Section: Resultsmentioning

confidence: 57%

Section: Ecg Datamentioning

confidence: 99%