Establishment of a new formula for QT interval correction using a large colony of cynomolgus monkeys

  • Nakayama Shunya
    Laboratory of Veterinary Physiology/Pathophysiology, Nihon University, College of Bioresource Science, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan
  • Koie Hiroshi
    Laboratory of Veterinary Physiology/Pathophysiology, Nihon University, College of Bioresource Science, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan
  • Kato-Tateishi Miyoko
    The Corporation for Production and Research of Laboratory Primates, 1-16-2 Sakura, Tsukuba, Ibaraki 305-0003, Japan
  • Pai Chungyu
    Laboratory of Veterinary Physiology/Pathophysiology, Nihon University, College of Bioresource Science, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan
  • Ito-Fujishiro Yasuyo
    Laboratory of Veterinary Physiology/Pathophysiology, Nihon University, College of Bioresource Science, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan
  • Kanayama Kiichi
    Laboratory of Veterinary Physiology/Pathophysiology, Nihon University, College of Bioresource Science, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan
  • Sankai Tadashi
    Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan
  • Yasutomi Yasuhiro
    Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan Mie University Graduate School of Medicine, Department of Molecular and Experimental Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
  • Ageyama Naohide
    Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan

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Description

<p> The demand for monkeys for medical research is increasing, because their ionic mechanism of repolarization is similar to that of humans. The QT interval is the distance between the Q wave and T wave, but this interval is affected by heart rate. Therefore, QT correction methods are commonly used in clinical settings. However, an accurate correction formula for the QT interval in cynomolgus monkeys has not been reported. We assessed snapshot electrocardiograms (ECGs) of 353 ketamine-immobilized monkeys, including aged animals, and contrived a new formula for the corrected QT interval (QTc) as a marker of QT interval prolongation in cynomolgus monkeys. Values for QTc were calculated using the formula [QTc] = [QT] / [RR]n, along with several other formulas commonly used to calculate QTc. We found that the optimal exponent of the QT interval corrected for heart rate, n, was 0.576. The mean value of QTc in healthy monkeys determined using the new formula was 373 ± 31 mm, and there were no significant differences between the sexes. Other ECG parameters were not significantly different between the sexes and there were no age-related effects on QTc. Prolongation of QTc to over 405 ms, as calculated by the new formula, was observed in 50 monkeys with underlying diseases. Additionally, all monkeys with QTc above 440 ms by the new formula had some underlying disease. The results resemble those in humans, suggesting that the new QTc formula could be useful for diagnosis of QT interval prolongation in cynomolgus monkeys.</p>

Journal

  • Experimental Animals

    Experimental Animals 69 (1), 18-25, 2020

    Japanese Association for Laboratory Animal Science

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