A method for recording electrocardiograms in conscious, unrestrained cynomolgus monkeys with emphasis on maximization of T wave amplitude

This communication describes an axial electrocardiogram (ECG) lead configur ation intended to record maximal T wave amplitudes of unrestrained consciou s cynomolgus monkeys. The impetus for this work came from the need to devel op a cynomolgus monkey model to evaluate potential effects of novel pharmac euticals on the QT interval. A large-animal model is needed as an alternati ve to the dog in instances involving atypical canine metabolism or overly s ensitive canine emetic responses to novel pharmaceuticals. Under anesthesia , a negative ECG lead teas implanted at the base of the right side of the n eck and a positive Lead was implanted under the left nipple, or fifth inter costal space near the sternum. Twenty-four-hour data collection occurred in the animals' home cages using radiotelemetry beginning at least 2 weeks fo llowing implant surgery. A total of 123 ECGs from 11 male and 3 female cyno molgus monkeys were analyzed across the physiologic range of heart rates (R R intervals of 300-900 ms). The longest RR intervals, which were in the 600 - to 900-ms range, were associated with QT intervals of 320-400 ms. These Q T and RR values occurred routinely in each of the monkeys during the dark p hase of the light/dark cycle and occasionally during periods of low physica l activity in the light phase. To the best of the authors' knowledge, publi shed investigations of the cynomolgus monkey QT interval did not include va lues recorded at RR intervals longer than 600 ms. Because it is now technic ally feasible to obtain high-quality ECGs from conscious, unrestrained, tel emetered cynomolgus monkeys at resting heart rates, the authors are in favo r of analyzing drug-related effects on QT intervals by comparing pre- and p ostdose QT intervals at similar heart rates or with Linear regressions rath er than by applying heart-rate adjustment formulas.