telemetry jackets did not impact the ability to accurately detectcardiovascular and neurobehavioral changes. The results demonstratethat an implanted telemetry device, a jacket containing inductivestraps, and modified neurobehavioral assessment techniques can beused to successfully evaluate cardiovascular, respiratory and neuro-behavioral function simultaneously in a single animal in the samestudy.

doi:10.1016/j.vascn.2011.03.132

Poster No: 127

Developmental assessment of the electrocardiogram (ECG) injuvenile canines using external telemetry and moxifloxacinCari M. Hudson, Marci L. Harter, Theodore J. Baird

Safety Pharmacology & Neurobehavioral Sciences, MPI Research,Mattawan, MI, USA

The use of juvenile animals on safety studies imparts insights tothe potential toxicity of drugs intended for the pediatric humanpopulation and is required by regulatory agencies as part of thenonclinical safety evaluation of therapeutics intended for thispopulation. One important function evaluated in juvenile studies isbasic cardiac electrophysiology. Due to variability inherent in ECGdeterminations based on environment, technique, and other subject-specific factors, it is essential that research facilities develop andmaintain appropriate test methodologies and historical control data.The objectives of this study were two-fold: 1) to pilot proceduresallowing periodic collection of ECGs using external telemetry fromuntreated juvenile to mature animals, and 2) to assess potentialdevelopmental differences in response to moxifloxacin, a drug whichpromotes hERG potassium channel mediated increase in QT/QTc.ECGs were collected monthly for 30 consecutive weeks utilizing theDSI JET system prior to and following administration of moxifloxacinor vehicle. Comparative data indicate considerably higher heart ratesand correspondingly shorter durations of RR, PR, and QT intervals inuntreated neonates. The magnitude of moxifloxacin-related cardio-vascular effects was similar at each developmental stage evaluated.Results indicate that external telemetry is amenable to use in near-neonatal and developing juvenile canines, and that ventricularrepolarization appears to be relatively uniformly affected by moxi-floxacin administration, regardless of age.

doi:10.1016/j.vascn.2011.03.133

Poster No: 128

Validation of JET™ (Jacketed External Telemetry) technology forECG and blood pressure assessment in the dogStephen C. Foote a, Jacob Holloway a, Adrianne Foote a, Peter Harris a,David Wolford b, Dingzhou Li c, Todd Wisialowski a, Jill Steidl a

a Global Safety Pharmacology, Pfizer Inc., Groton, CT, United Statesb Bioanalytical Toxicology, Pfizer, Inc., Groton, CT, United Statesc Pharma Therapeutics Biostatistics, Pfizer Inc., Groton, CT, United States

The aim of this work was to assess the quality and sensitivity of ECGand blood pressure data acquired using JET in single andmulti-dose dogsafety studies. A modified catheter was placed in the femoral artery ofdogs formeasurement of blood pressurewith a rodent telemetry device(PA-C40). ECG (surface lead II configuration) and blood pressure signalswere continuouslymeasured in jacketed animals. Acclimation to jackets

with concurrent data acquisitionwasperformed over five sessions of 7 hin duration and results indicate that 3 days is sufficient for animals tobecome accustomed to the jackets. Positive control agents were testedwith JET in a crossover design and results were comparable to thosegenerated with implantable telemetry. Doxazosin (0.3, 1, and 3 mg/kg),decreased blood pressure by 9, 11 and 15 mm Hg and increased heartrate by 6, 13 and 28 bpm, respectively. Moxifloxicin (10, 30, and 90 mg/kg) increased QTc by 6, 16 and 31 ms, respectively. To furthercharacterize JET sensitivity, a power analysis was performed on both7 hour data generated using a crossover study design and 24 hour datagenerated using a repeat dose toxicology study design. These analysesdemonstrate that JET is a highly sensitive model for characterization ofdrug-induced ECG and hemodynamic changes in acute or chronicstudies.

doi:10.1016/j.vascn.2011.03.134

Poster No: 129

Exploring filtering and correction factors in a standard dogcardiovascular modelMonica R. Metea a, Thomas J. Vidmar b,Laurie J. Shellhammer a, Philip R. Atterson a

a WIL Research Laboratories, LLC, Ashland, OH, United Statesb BioSTAT Consultants, Portage, Michigan, United States

As beat-by-beat cardiovascular data collection is becoming astandard practice, the approaches for processing large amounts ofdata need to be reassessed. The aim of this study was to exploreanalysis methods of beat-by-beat data collected and processed usingDSI Ponemah v4.8, and compare frequently used correction formulas.

Methods: Eight telemetry-implanted beagle dogs were dosed in aLatin Square design with moxifloxacin at 5, 30, and 100 mg/kg andcardiovascular parameters were continuously acquired. Heart rate-corrected QT interval was calculated using Van deWater's, Fridericia'sand Bazett's formulas or individual animal corrections and thedifferences from the zero reference for QT correction slopescomputed. Four filtering paradigms for removal of noise and artifactswere compared using either automated filters or manually placedmarks followed by interval-based filters applied for each method.Each filtering paradigm was analyzed with repeated-measureanalysis of covariance.

Results: 1) Statistical analysis conducted separately for eachfiltering method showed similarity of effects; 2) QTcV and QTcFshowed the best correction for all dose groups (slopes notsignificantly different from zero). Individual correction factors didnot perform better than the standard methods. 3) The QT prolonga-tion corresponding to 80% power of detection confirmed that a 4×4Latin Square design remains a suitable choice.

doi:10.1016/j.vascn.2011.03.135

Poster No: 130

Comparison of two chronically-instrumented conscious dogmodels for assessment of cardiovascular function insafety pharmacologyEric Delpy, Fabrice Infanti,Myriam Garreau, Christophe Drieu La Rochelle

Biotrial Pharmacology, Non-Clinical Pharmacology Department,Rennes, France

Abstractse38