Age-related differences of QT interval and autonomic nervous system activity in female cynomolgus monkeys.
BACKGROUND
Cynomolgus monkeys are used in in vivo toxicological studies to evaluate the effects of drug candidates on the cardiovascular system, especially the effects of drugs on the QT interval on the electrocardiogram (ECG). Aging is reportedly one of the factors influencing the QT interval, but data from old monkeys have not been available.


METHODS
The ECG parameters, including the QT interval and rate-corrected QT intervals calculated using Bazett's formula (QTcB) or individual correction factors (QTcI), in old female monkeys (the old group, n=7, average age=25.1+/-1.1 years) or young female monkeys (the young group, n=7, average age=4.4+/-0.2 years) were assessed by Holter electrocardiogram monitoring. The prolongation of QT interval induced by dl-sotalol, a representative class III antiarrhythmic drug, was also evaluated. In addition, power spectral analysis of heart rate variability was conducted.


RESULTS
The QT interval in the old group was shorter than that of the young group during the dark period. The power spectral analysis of the ECG revealed quite a difference in autonomic nervous system activity between old and young animals. The prolongations of the QT interval, QTcB and QTcI after oral administration of 3 mg/kg dl-sotalol in the old group tended to be greater than those in the young group, and the QT interval in the old group was significantly longer than that in the young group at 1 h after dosing of dl-sotalol.


CONCLUSIONS
The present study revealed some of the influences of age on the QT interval in female cynomolgus monkeys. There may be age-related differences in the circadian variation of QT interval or the drug-induced QT interval prolongation in this species.
Ishizaka
Tomomichi
T
Medicinal Safety Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Japan. ishizaka.tomomichi.du@daiichisankyo.co.jp
Yoshimatsu
Yu
Y
Ozawa
Minori
M
Kimotsuki
Tomofumi
T
Takasaki
Wataru
W
Manabe
Sunao
S
Yasuda
Mitsuya
M
D000367:Age Factors; D000375:Aging / Q000097:blood* / Q000502:physiology*; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D004562:Electrocardiography; D005260:Female; D008133:Long QT Syndrome / Q000097:blood* / Q000503:physiopathology*; D008252:Macaca fascicularis