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Comparison of freely-moving telemetry Chinese Miniature Experiment Pigs (CMEPs) to beagle dogs in cardiovascular safety pharmacology studies.

Abstract：

INTRODUCTION:Telemetry beagle dogs are the most frequently used species in cardiovascular telemetry assessments. However, beagle dogs may not be always suitable for all of the tests. Recently minipigs have received increased attention for these studies. Differences between the two species regarding the response of their cardiovascular systems to environmental stimuli are unclear. This study investigates how the telemetry minipig compares to beagle dog as a test subject and also refines the experimental protocols necessary to obtain accurate data. METHODS:Beagle dogs and Chinese Miniature Experiment Pigs (CMEPs) were implanted with telemetry transmitters and the influences of gavage, feeding and the circadian cycle on various cardiovascular parameters were investigated. RESULTS:ECG signal quality from CMEPs was superior to that of the beagle dogs. Poor ECG signal quality, elevated HR, BP and locomotor activity associated with gavage and feeding were observed in both species. ECG signal quality, BP and locomotor activity recovered more quickly in the CMEPs than in the beagle dogs. Residual elevation of HR found in CMEPs lasted approximately 4h post-feeding, which has a profound influence on the circadian cycle. A diurnal rhythm in CMEP with a significant increase of body temperature during the dark period and a clear circadian rhythm of locomotor activity in both species were observed. DISCUSSION:The present data demonstrated that gavage, feeding and circadian cycle were having an enormous influence on BP, HR and locomotor activity in both species. If drug-induced effects are expected rapidly after oral administration and feeding, CMEP seems to be a favorable choice. Also, due to the effects of feeding on HR, CMEPs should fast at least 5h before the start of recording or should not be fed during the study where the Tmax of a given compound might occur very late. It also should be taken into consideration when the test article has a potential effect on body temperature by using CMEPs. In summary, the telemetry CMEP is a valuable alternative to the beagle dog for cardiovascular telemetry studies.

journal_name

J Pharmacol Toxicol Methods

journal_title

Journal of pharmacological and toxicological methods

authors

Yuan H,Zhao J,Guo J,Wu R,He L,Cui Y,Feng M,Zhang T,Hou M,Guo Q,Zhang L,Jia L,Huang C,Ye L,Peng S

doi

10.1016/j.vascn.2014.03.172

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

19-28

issue

eissn

1056-8719

issn

1873-488X

pii

S1056-8719(14)00209-3

journal_volume

pub_type

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Comparison of freely-moving telemetry Chinese Miniature Experiment Pigs (CMEPs) to beagle dogs in cardiovascular safety pharmacology studies.