Poster Presenter
Characterization of Baseline Cardiovascular Functions in the Conscious
Freely-Moving Juvenile Non-Human Primate
Ali S. Faqi, John C. Resendez, and Theodore J. Baird
USA
Most nonclinical/clinical drug safety assessments are
conducted in developmentally mature subjects, which may not represent
the most appropriate test sample for evaluating compounds with pediatric-specific
indications. When children are the primary population, age-appropriate
studies in juvenile animals are important for assessing direct toxic
or developmental risks. With emerging trends in biologics, the necessity
of conducting juvenile toxicology studies in non-human primates
(NHP) will likely increase.
The purpose of this study was to characterize the postnatal developmental
progression of key cardiovascular safety endpoints in 7-14 month
old juvenile NHPs. To assure a comprehensive evaluation, utilizing
continuous data sampling procedures without complications associated
with chemical or physical restraint; eight recently weaned cynomolgus
macaques were surgically instrumented with radiotelemetry transmitters
to measure systemic arterial pressures and body temperature, and
to record a standard electrocardiogram (ECG). A pressure-sensitive
catheter was introduced femorally and positioned within the descending
aorta, and bipolar electrode implanted to record a Lead II ECG.
To facilitate long-term vascular access, a femoral venous catheter
was implanted and connected to a subcutaneous vascular access port.
Heart rate, blood pressure, body temperature and the ECG were collected
according to a bi-weekly schedule using PoNeMah (Ver 4.1) software.
Telemetry data, including standard ECG reference intervals (RR,
PR, QRS, QT, QTc), heart rate, blood pressure, body temperature
will be presented and compared to a reference historical control
dataset previously collected from a large sample of adult NHP subjects
(Gauvin et al., 2006, J Pharmacol Toxicol Methods 53:140-51). The
nature and putative bases for observed differences in baseline values
for these physiological variables between adult and developing juvenile
animals will be discussed.
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