an innovative surgical technique for telemetry ecg lead placement in cynomolgus monkeys (macaca...

Poster No: 150

Long-term assessment of Non-Human Primate (NHP) ECG usingJacketed External Telemetry (JET): Evaluation of heart rate andQTc interval variation over 6 months of observationRay W. Chui, Kathy Derakhchan, Hugo M. Vargas

Investigative Toxicology, Amgen Inc., Thousand Oaks, CA, USA

Non-invasive ECG recording with JET can be used to assess cardiacelectrical activity in non-rodent toxicology (tox) studies. Given thatthe duration of tox studies can vary, e.g, days to months, there is aneed to assess ECG changes over long time periods. In this study, JETwas used to monitor heart rate (HR) and QTc intervals in NHP over6 months to assess normal HR/QTc variation over the time-frame of along-term tox study. Six male cynomolgus monkeys were acclimatedto JET (3 jacketings/2 wks) during pre-study and prior to the 6 monthrecording (days: 134, 137, 142). On study days −7 (prestudybaseline), 1, 22 and 178, JET-derived HR/QTc data were recorded for24 hr; NHP were given vehicle (5 ml/kg PO) at time 0 on each day. Onday −7, values (mean±SD) for HR were 115±24 bpm and QTc were339±12 msec at time 0 (10 AM) and showed a normal circadianpattern (mean range: 90–148 bpm; 333–354 msec, respectively) overthe following 24 hr period. On days 1 & 22, HR and QTc values were inthe same range as pre-study values, thus stable and consistent. After along break, NHP were re-acclimated to JET (see above) to emulateECG recording at 6 months. On day 178, HR (mean range: 108–125 bpm) and QTc intervals (mean range: 316–337 msec) weresimilar to values derived on study days 1 and 22. Over the 6 monthstudy, NHP were jacketed 15 times. Overall, these findings demon-strate that JET-ECG can be used in short- and long-term tox studies, iseasy to implement, is well tolerated by NHP, and yields reproducible,high quality ECG data.

doi:10.1016/j.vascn.2011.03.156

Poster No: 151

Comprehensive arrhythmia analysis in telemeterednon-human primatesRay W. Chui a, Kathy Derakhchan a, Emily Nolan b, Hugo M. Vargas a

a Investigative Toxicology, Amgen Inc., Thousand Oaks, CA, USAb EMKA Technologies USA, Falls Church, VA, USA

The occurrence of drug-induced arrhythmia in safety pharmacol-ogy or toxicology studies is a primary safety concern, but the riskassessment requires an accurate knowledge of background arrhyth-mia frequency in the test species. The purpose of this study was todetermine the normal frequency of arrhythmias in a colony oftelemetered cynomolgus monkeys, since there is a data gap inbackground arrhythmias in this species. To conduct this analysis,continuous ECG data (24 hr) were recorded from 18 telemetry-instrumented monkeys on 3 separate days, over an 8 day period. Foreach animal, an arrhythmia waveform library was manually created,then applied to the waveform file using EMKA ecgAuto, a patternrecognition-based software application. On day 1, 9/18 monkeysshowed at least 1 premature ventricular contraction (PVC; range: 0–9), with 2/18 showing 1 incidence of supraventricular prematurecomplexes (SPC). On day 4, a similar pattern emerged: 5/18 monkeysshowed at least 1 PVC (range: 0–12) and 3/18 had 1 incidence of SPC.On day 8, 7/18 NHP displayed at least 1 PVC and 1/18 had a SPC. Otherarrhythmias were noted sporadically: right bundle branch block,wandering pacemaker, SA node pause. The pattern of arrhythmia was

relatively consistent in each NHP. These findings suggest that a single24 hr assessment period may be insufficient to determine arrhythmiabackground. A best practice recommendation is to determine thebackground arrhythmia rate in each telemetry animal to aidinterpretation of potential proarrhythmic properties of new testarticles.

doi:10.1016/j.vascn.2011.03.157

Poster No: 152

An innovative surgical technique for telemetry ECG leadplacement in cynomolgus monkeys (Macaca Fascicularis)Simon Authier a, Michael Stonerook b, Eric Troncy c,Sebastien Fournier a, Boyce Moon d

a LAB Research Inc. Laval, Quebec, Canadab Vertex, Cambridge, MA, USAc Faculty of Veterinary Medicine, Universit de Montreal, St-Hyacinthe,Quebec, Canadad Data Science International (DSI), New Brighton MN, USA

Electrocardiograms (ECG) in cynomolgus monkeys are requiredsafety pharmacology investigations. Telemetry enables continuous ECGmonitoring and is considered the gold standard to meet regulatoryrequirements for safety assessments in non human primates. In recentyears, different ECG leads have beenusedwithmixed results: DerivationII (DII) subcutaneous ECG leads (significant electromyogram artifactsand low p-wave amplitude); Intracardiac leads (various complicationsincluding cardiac chamber perforation); DII ECG leads placement (+)apex of the heart, (−) 4th intercostals space (low P-wave amplitude);Pericardiac ECG lead placement associated with adequate ECG mor-phologyand amplitudewithminimal EMG interferences but requires aninvasive thoracotomy. The current study evaluated a DII telemetry ECGlead placement with the positive lead sutured to the diaphragm at thelevel of theheart apex and thenegative lead inserted through the jugularvein and advanced to ¾ inch above the right atria as confirmed withfluoroscopy imaging during surgery. This telemetry ECG lead implanta-tion technique resulted inhighamplitudeQRS complexes (meanR-waveamplitude of 3.4 mV) and P-waves (mean P-wave amplitude of 0.8 mV)which facilitated computerized interval measurements. Average signalto noise ratio was 270.9 ±58.7 for R-wave and 63.6±11.6 for P-wave.The technique also provided stable ECG complex morphology withminimally invasive surgical procedures.

doi:10.1016/j.vascn.2011.03.158

Poster No: 153

Utilization of jacketed external telemetry (JET) in conscious,non-human primates (NHP) over 1, 4, and 7 months:Acclimation considerationsKathy Derakhchan, Ray W. Chui, Hugo M. Vargas

Investigative Toxicology, Amgen Inc., Thousand Oaks, CA, USA

Non-invasive electrocardiogram (ECG) data capture with a jacketsystem can optimize ECG evaluation in toxicology (tox) studies, byreducing stress associated with chemically or physically-restrainedanimals for ECG and heart rate (HR) assessment, and enablingcontinuous data collection. The purpose of this study was to assess

Abstracts e45