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


CONCLUSIONS
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.
Department of Occupational and Environmental Health, School of Public Health, Jilin University, 1163 Xin Min Street, Changchun 130021, China; Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Haitao
H
Yuan
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Jing
J
Zhao
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Jiabin
J
Guo
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Ruiqin
R
Wu
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Li
L
He
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Yaxiong
Y
Cui
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Min
M
Feng
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Tingfen
T
Zhang
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Mingyue
M
Hou
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Qian
Q
Guo
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Lijun
L
Zhang
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Li
L
Jia
Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China.
Chang
C
Huang
Department of Occupational and Environmental Health, School of Public Health, Jilin University, 1163 Xin Min Street, Changchun 130021, China. Electronic address: jlyelin@163.com.
Lin
L
Ye
Department of Occupational and Environmental Health, School of Public Health, Jilin University, 1163 Xin Min Street, Changchun 130021, China; Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Rd., Fengtai district, Beijing 100071, China. Electronic address: pengsq@hotmail.com.
Shuangqing
S
Peng
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D001831:Body Temperature / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System; D002940:Circadian Rhythm / Q000502:physiology; D004285:Dogs; D004562:Electrocardiography / Q000379:methods / Q000662:veterinary; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000502:physiology; D013552:Swine; D013556:Swine, Miniature; D013686:Telemetry / Q000009:adverse effects* / Q000379:methods* / Q000662:veterinary
Beagle dog; Cardiovascular safety pharmacology; Chinese Miniature Experiment Pig; Circadian cycle; Feeding; Gavage administration; Telemetry