incidence of arrhythmia in cynomolgus monkeys instrumented for telemetry with epicardial (epi) ecg...

with moxifloxacin was detected adequately and was comparablebetween the two methods. The correlation coefficients, measuringthe strength of the relationship between the two methods were >0.9,for most of the parameters tested. In addition, for most variables, thepoints aligned close to the line of identity, indicating that the twomethods measured the same values.

doi:10.1016/j.vascn.2011.03.152

Poster No: 147

Comparative assessment of different telemetry data analysismethods using dl-sotalol in beagle dog and rhesus monkeysMin Deng, Patrick A. Fanelli, Jude W. Ferraro, Holly McPherson,Tara Grady-Styring, Michael Magee, William Keller,Chao-min Hoe, Kimberly Hoagland

Merck & Co., Inc. West Point, PA, USA

Telemetry studies generate large electronic data files, so it isimportant to consider analysis methods when evaluating magnitudeand duration of test compound effects. We analyzed dog and monkeytelemetry data after oral doses of of dl-sotalol using 5 different dataanalysis paradigms: (1) continuous 15-min means, (2) continuous 1-hr means, (3) the first 15 min of every hr, (4) 1-min means atselected times and (5) a phase analysis, using progressive increases indata bin size. The aim was to compare data profiles using theseanalysis methods and to evaluate aspects of these methods for dogversus monkey studies. In both the dog and monkey studies,increases in PR, QT and QTc intervals were apparent in all 5paradigms, but there was less resolution with method #5, since thedata reduction level is greatest. In addition, circadian rhythm for QTinterval in the monkey study was not evident for analysis method #5.Data profiles for methods #2 and #3 were similar, suggesting thatdata reduction within 1-hr data bins does not impact resolution, anobservation that may be important when analyzing “noisy” data sets(surface ECG data or during a high level of interference) or whenissues with accurate marking of ECG waveforms occur. In conclusion,data analysis methods should be carefully selected when designingtelemetry studies, taking into account degree of data resolutiondesired and impact of data reduction methods. Importantly, themethods chosen may differ for species that exhibit a circadian rhythmfor cardiovascular parameters (monkeys, rats and mice).

doi:10.1016/j.vascn.2011.03.153

Poster No: 148

Evaluation of a pericardial electrocardiography model intelemetered cynomolgus monkeysJohnny Yao, Todd Littell, Laura Schnee, David Yates

Pfizer, Pearl River, New York, USA

Subcutaneous (SC) ECG lead placement in telemetered nonhumanprimates typically results in poor quality ECG signals due to lowsignal relative to muscle noise. Intracardiac (IC) ECG lead placementimproves ECG signal quality; however, a prolonged period ofpostsurgical (PS) signal stabilization and a high incidence ofmechanical malfunction proved to be significant limiting factors withthis model. In an effort to further refine ECG lead placement in the

nonhuman primate to optimize signal quality, reliability and long-evity of the animal model, we developed and evaluated a modifiedpericardial (PC) ECG lead placement.

Methods: A modified PC lead placement was evaluated in 12cynomolgus monkeys. Heart rate (HR), mean arterial blood pressure(MABP) and ECGs were monitored telemetrically for a period of12 months after implantation.

Results: The PC ECG had large voltage amplitude on the majorwaves (3–6 mV for R or S wave) and low muscle noise. The waveformmorphology of PC ECGs was similar to that recorded fromsubcutaneous leads, and showed minimal changes during the PSrecovery period. ECG parameters (PR, QRS, and QT intervals)stabilized in 72 hrs PS. The HR recovered from 197±8 (mean±SEM) immediately PS to 141±6 and 136±8 bpm at 48 and 72 hrsPS, respectively. The MABP recovered from 118±5 immediately PS to94±3 and 91±5 mmHg at 48 and 72 hrs PS, respectively. The HRand MABP remained at 133±13 bpm and 81±5 mmHg, respectivelyat 12 months PS.

Conclusions: Pericardial ECG placement provides a clear, stableECG signal with prompt postsurgical stabilization.

doi:10.1016/j.vascn.2011.03.154

Poster No: 149

Incidence of arrhythmia in cynomolgus monkeys instrumentedfor telemetry with epicardial (EPI) ECG lead orientationDavid L. Holdsworth a, Kyle P. O Donohue a,Francis W.K. SmithJr. b, Theodore J. Baird a

a Safety Pharmacology & Neurobehavioral Sciences, MPI Research,Mattawan, MI, USAb VetMed Consultants, Lexington, MA, USA

Procedures for ECG lead placement associated with implantabletelemetry have evolved over time in the interest of minimizingartifact and enhancing the quantitative evaluation of ventricularrepolarization (QT interval). However, high fidelity ECG records arealso necessary for detailed qualitative review. Many investigatorshave found that EPI placement most consistently yields the bestsignal quality. As an increase in ventricular arrhythmia haspreviously been demonstrated after trans-ventricular (LV) instru-mentation in cynomolgus monkeys, which included EPI ECG leadplacement, this investigation was conducted to determine theincidence of arrhythmia following EPI placement alone, i.e., withoutLV catheterization. The general method of this laboratory is to attachthe positive lead to the left ventricular free wall near the apex andthe negative lead near the mediastinal aspect of the base of theheart. Approximately 24 hours of continuous ECG telemetry datawere reviewed from ~50 monkeys post-surgery. Limited arrhythmiawas noted overall, and when present, typically <10 episodes overthe entire 24- hour period. Occurrences of single, periodic VPCswere the primary finding. These findings are markedly less than aprior study of LV instrumented monkeys in which 35/67 subjects(52%) had >10 VPCs within a single hour, at times including variousclearly abnormal variants (e.g., ventricular tachycardia). Details ofthe current experimental methodology and implications of thesefindings for quantitative and qualitative evaluations in safety studieswill be discussed.

doi:10.1016/j.vascn.2011.03.155

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