Cynomolgus monkeys are closely related to humans phylogenetically, and this has resulted in their widespread use as a preclinical model. Hematological data with regard to these monkeys are thus important. Although reference values for blood components and sex hormones have been established for cynomolgus monkeys, those for arterial blood gases have not. The arterial blood gases quickly reflect respiratory and circulatory dynamics, and are thus useful for animal management and safe general anesthesia and surgical operations. Furthermore, since O2 is transported by RBC, CBC and blood gases are closely related. The present study aimed to establish reference values for arterial blood gases and CBC in cynomolgus monkeys over a wide age range. Blood gases and CBC of arterial blood, collected from 41 female and 21 male anesthetized monkeys, were measured. Age correlated with RBC, HGB and HCT in the CBC. Values differed significantly between males and females in pCO2, CO2 concentration, MCV and MCH. The pH of blood was equivalent to that of humans and pCO2 was more stable, whereas MCV and MCH were lower than those in humans. Erythrocytes were smaller and less pigmented than in other Macaca species. Several relationships between gender and age, and blood gases and CBC were identified in cynomolgus monkeys. In conclusion, these reference values will be useful as markers for veterinary applications and in the care and maintenance of these animals.
Various cardiovascular diseases can be detected and diagnosed using echocardiography. The demand for cardiovascular system research using nonhuman primates is increasing, but echocardiographic references for nonhuman primates are limited. This report describes the first comparison of echocardiographic reference values in 247 normal cynomolgus monkeys (135 females, 112 males) over a wide age range. Echocardiography, electrocardiography, blood pressure and chest X-ray images were acquired under immobilization with intramuscular ketamine hydrochloride, then cardiac structure, function, and flow velocity were assessed. Cardiac hormone levels were also tested. We found that cardiac structures positively correlated with weight, that the size of these structures stabilized after reaching maturity and that cardiac output increased according to heart size. In contrast, fractional shortening of the left ventricle, ejection fraction and flow velocity showed no significant correlations with weight or age, and age and E wave correlated negatively. These findings appear sufficiently similar to those in humans to suggest that cynomolgus monkeys can serve as a suitable model of human cardiac disease. Our data should also prove useful for surveying cardiac dysfunction in monkeys.
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.
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