TY - JOUR
T1 - Establishment of a new formula for QT interval correction using a large colony of cynomolgus monkeys
AU - Nakayama, Shunya
AU - Koie, Hiroshi
AU - Kato-Tateishi, Miyoko
AU - Pai, Chungyu
AU - Ito-Fujishiro, Yasuyo
AU - Kanayama, Kiichi
AU - Sankai, Tadashi
AU - Yasutomi, Yasuhiro
AU - Ageyama, Naohide
N1 - Publisher Copyright:
© 2020 Japanese Association for Laboratory Animal Science.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Cardiovascular disease
KW - Cynomolgus monkey
KW - Electrocardiogram
KW - QT interval
KW - The corrected QT interval
UR - http://www.scopus.com/inward/record.url?scp=85078692839&partnerID=8YFLogxK
U2 - 10.1538/expanim.19-0009
DO - 10.1538/expanim.19-0009
M3 - Article
C2 - 31308302
AN - SCOPUS:85078692839
SN - 1341-1357
VL - 69
SP - 18
EP - 25
JO - Experimental Animals
JF - Experimental Animals
IS - 1
ER -