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

Abstract

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.

Echocardiographic evaluation of cardiac function in cynomolgus monkeys over a wide age range

“…We were unable to measure E wave deceleration because cynomolgus monkeys have rapid heart rates. Compensatory buffer systems noted in the present study have also been identified in humans [ 22 , 27 ]. Monkeys seem to have a similar cardiovascular system to that of humans and a buffering LV diastolic function that differs from that of other animals.…”

“…We were unable to measure E wave deceleration because cynomolgus monkeys have rapid heart rates. Compensatory buffer systems noted in the present study have also been identified in humans [22,27]. Monkeys seem to have a In this study, we applied screening tests such as chest X-ray (A) and ECG (B) for all monkeys.…”

“…Heart rate affects CO because they are calculated as SV × heart rate. However, heart rates do not change with aging in cynomolgus monkeys [22]. We suggest that the nature of changes in CO in the present study was due to this influence.…”

“…This study used only healthy monkeys showing no abnormalities on ECG, X-ray ( Fig. 1) or blood tests, including cardiac hormones (Table 2), compared with our previous reports [21,22]. This study proceeded according to the Rules for Animal Care and Management of the Tsukuba Primate Research Center, the Guiding Principles for Animal Experiments Using Nonhuman Primates formulated by the Primate Society of Japan [10,23] and the Guide for the Care and Use of Laboratory Animals [13].…”

Usefulness of cardiac hormones for evaluating valvular disease in cynomolgus monkeys (<i>Macaca fascicularis</i>)

“…Although VD in nonhuman primates has been receiving a lot of attention in the human medical field [ 2 , 9 , 24 ], there has been no report on the usefulness of cardiac hormones for the diagnosis of VD in monkeys.…”