Assessment of two external telemetry systems (PhysioJacket and JET) in beagle dogs with telemetry implants.
BACKGROUND
Regulatory guidelines recommend the use of conscious, unrestrained animals for comprehensive cardiovascular safety assessment of a new therapeutic agent. Cardiovascular safety pharmacology studies normally use internal telemetry (surgical implants) in free-moving animals to monitor key ECG endpoints, like the QTc interval, but this technical approach is highly resource intensive. In toxicology studies, ECG recording is also typically performed under chemical or physical restraint, which has a number of disadvantages, e.g., anesthesia confounds, handling stress and limited data collection. External telemetry for ECG recording has the potential to overcome many of these restraint limitations, with the benefit of being a surgically non-invasive method. To evaluate this method, we used two jacket systems: Data Sciences International (DSI) JET and Integrated Telemetry Systems (ITS) PhysioJacket in implanted beagle dogs.


METHODS
Heart rate and cardiac intervals were monitored continuously for 22-24 h following oral administration of vehicle (water) or 1 mg/kg E-4031. Data obtained from each jacket system was compared with implant-derived data in the same animal.


RESULTS
Significant increases in QT/QTcV (25-30 ms) were noted following treatment with 1 mg/kg E-4031 in both external jacket systems and with implanted telemetry. Throughout the recording periods, the normal variations in heart rate and ECG intervals observed in conscious dogs as detected with the jacket systems, mirrored the changes observed via implant telemetry.


CONCLUSIONS
The overall findings from this study support the use of external telemetry technology as a viable alternative to implants. The data demonstrated that jackets were sufficiently sensitive to detect QT/QTcV changes following E-4031 administration, that were comparable to those derived from implants. As such, this method is an invaluable tool for obtaining high quality ECG data from repeat-dose toxicology studies.
Investigative Toxicology, Amgen, Inc., Thousand Oaks, CA 91320, USA.
Ray W
RW
Chui
Abigail
A
Fosdick
Ra'Shun
R
Conner
Jian
J
Jiang
Bernd A
BA
Bruenner
Hugo M
HM
Vargas
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004562:Electrocardiography / Q000295:instrumentation* / Q000379:methods; D004864:Equipment and Supplies; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D023421:Models, Animal; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology; D013686:Telemetry / Q000295:instrumentation* / Q000379:methods
D000889:Anti-Arrhythmia Agents; D051638:Ether-A-Go-Go Potassium Channels; D010880:Piperidines; D011725:Pyridines; C063968:E 4031