ECG telemetry in conscious guinea pigs.
BACKGROUND
During preclinical drug development, monitoring of the electrocardiogram (ECG) is an important part of cardiac safety assessment. To detect potential pro-arrhythmic liabilities of a drug candidate and for internal decision-making during early stage drug development an in vivo model in small animals with translatability to human cardiac function is required.


METHODS
Over the last years, modifications/improvements regarding animal housing, ECG electrode placement, and data evaluation have been introduced into an established model for ECG recordings using telemetry in conscious, freely moving guinea pigs. Pharmacological validation using selected reference compounds affecting different mechanisms relevant for cardiac electrophysiology (quinidine, flecainide, atenolol, dl-sotalol, dofetilide, nifedipine, moxifloxacin) was conducted and findings were compared with results obtained in telemetered Beagle dogs.


CONCLUSIONS
Under standardized conditions, reliable ECG data with low variability allowing largely automated evaluation were obtained from the telemetered guinea pig model. The model is sensitive to compounds blocking cardiac sodium channels, hERG K(+) channels and calcium channels, and appears to be even more sensitive to β-blockers as observed in dogs at rest. QT interval correction according to Bazett and Sarma appears to be appropriate methods in conscious guinea pigs. Overall, the telemetered guinea pig is a suitable model for the conduct of early stage preclinical ECG assessment.
Safety Pharmacology, Bayer Pharma AG, Wuppertal, Germany.
Sabine
S
Ruppert
Safety Pharmacology, Bayer Pharma AG, Wuppertal, Germany.
Thomas
T
Vormberge
Research & Clinical Sciences Statistics, Bayer Pharma AG, Berlin, Germany.
Bernd-Wolfgang
BW
Igl
Safety Pharmacology, Bayer Pharma AG, Wuppertal, Germany. Electronic address: michael.hoffmann@bayer.com.
Michael
M
Hoffmann
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004562:Electrocardiography / Q000295:instrumentation* / Q000379:methods*; D004567:Electrodes, Implanted; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015203:Reproducibility of Results; D013686:Telemetry / Q000295:instrumentation* / Q000379:methods*
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers
ECG; Early stage drug development; Guinea pigs; QT interval correction; Social animal housing; Telemetry method