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Comparison of Non-Invasive versus Invasive Telemetry
Derek Hunter, Jason Schofield, Katy Gracie, Jackie Moors, Karen Philp, Helen Prior, Jean-Pierre Valentin & Tim Hammond. Safety
Pharmacology, Safety Assessment UK, AstraZeneca UK Ltd, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
Historically, physiological monitoring on canine toxicity studies has been limited to recording a conventional
To evaluate 2 different telemetry systems; (i) invasive telemetry (DSI telemetry – acquisition and analysis Notocord
electrocardiogram (ECG). Measurements, therefore, are restricted by practical limitations to "snap-shot"
recordings (aimed at Cmax), leaving gaps when changes in physiological parameters and any transient
(ii) non-invasive telemetry (EMKA jacket system – acquisition and analysis IOX 1.7.0 and ECGAuto 1.5.7).
cardiotoxicity, particularly in the ECG parameters, would go undetected. New technological advances in non-invasive telemetry systems may allow some inclusion of quality ECG measurements for longer time periods in
Does the EMKA system give the same results as the DSI/Notocord system with a known reference
toxicological (or other) studies, thus reducing animal usage and compound requirements.
Figures 1 a-d : Correlation Plots
Six male Alderley Park beagle dogs implanted with DSI TL11
Pharmacological Validation - Figure 1a
Pharmacological Validation - Figure 1b
Pharmacological Validation - Figure 1c
Pharmacological Validation - Figure 1d
M2 D70-PCT devices had external skin ECG electrodes placed in lead II configuration and wore jackets containing the EMKA
Each dog was recorded from its home pen (4.5m2) containing
DSI receivers and EMKA antennae. ECGs were acquired
simultaneously using both systems in freely moving animals.
Increasing doses of (±) sotalol at 1-2 day intervals (4, 8, 16
mg/kg) were orally administered with control on day 1.
Continuous recording on each day was 1h of baseline and 6h
post-dose (sample frequency 500Hz), the same 1 min of data
was reported. All data was100% QC’d and hand-measured if
QTcV - DSI
Figures 2 a-b : QT versus RR Plots
QT vs RR EMKA (0, 4, 8 & 16 mg/kg) - Figure 2a
QTvs RR DSI (0, 4, 8 & 16 mg/kg) - Figure 2b
Acceptance criteria for the this comparison is 5% between both systems for all parameters.
Potential Differences were expected, due to:
•Event marker input into each system may be 1-2 heart beats
asynchronous, which may slightly affect minute averages.
•Good correlation between data from EMKA and DSI systems
•Data for all parameters, except QRS duration, within
•Variation of QRS dataset on all days consistent EMKA >DSI
•Small differences probably due to definition of QRS segment
•Peak QT effects (% increase of 16 mg/kg sotalol vs control)
RR Interval (ms)
RR Interval (ms)
ECG data acquired by the EMKA system is complementary to DSI with the exception of QRS duration, however, the QRS differences are consistent.
The EMKA system generates high quality ECG data adding real value to toxicological and/or safety pharmacology studies.
The EMKA system will have a major impact on the 3Rs (Refinement, Reduction & Replacement).
QTcV for both systems generated a tight dose response to (±) sotalol.
However, advantages of the DSI invasive telemetry system is its combination with arterial blood pressure (and other parameters such as body temperature, left ventricular
pressure/pleural pressure), permitting a complete cardiovascular core battery assessment. This allows a colony of dogs to be dedicated for Safety Pharmacology studies,
with the possibility of re-use over many months.
Advantages of the EMKA non-invasive telemetry system is the lack of surgery, and thus animal welfare improvement, however, training for acceptance of jackets is
required as this may induce some stress.
Additionally, for repeat-dosing Safety Pharmacology study designs (perhaps as a ‘follow-up’ study), a potential use would be to include these EMKA ECG measurements
QT Vehicle (EMKA)
QT Sotalol 16mgkg (EMKA)
on specific days during an appropriate dog toxicology study (eg, 7 day repeat phase of MTD, or 28 day regulatory tox study), thus gaining a higher quality of ECG results than conventional ‘snap-shot’ recordings, as well as reducing the requirement for a separate telemetry study (with the animal welfare, compound requirement and resource
QT Vehicle (DSI)
QT Sotalol 16mgkg (DSI)
1 Einleitung _____________________________________________________________ 3 2 Datenmaterial __________________________________________________________ 3 3 Die neuen Wirkstoffe des Jahres 2004 ______________________________________ 4 Übersicht der Wirkstoffe__________________________________________________ 4 Die Bedeutung der Wirkstoffe im Jahr 2005____
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