Determinants of cardiac electrophysiological properties in mice.
BACKGROUND
The transgenic mouse is a popular model for human inherited cardiac disease. Electrophysiology (EP) studies have recently been performed in transgenic mice to characterize the electrical phenotype of the heart. However, little is known regarding the impact of experimental conditions or model selection on the outcome of EP studies in mice.


RESULTS
We investigated the effects of experimental conditions on mouse cardiac EP by (1) comparing the findings of transesophageal pacing with those of invasive intracardiac pacing, (2) elucidating the effects of commonly used anesthetic agents, and (3) determining the impact of changes in body temperature. We also investigated the effects of model selection by (1) studying the dependence on mouse strain, and (2) exploring the effects of age. We found that EP parameters derived by both transesophageal and intracardiac pacing/recordings methods were similar. On the other hand, the anesthetic mixture of ketamine, xylazine, and acepromazine had profound effects on cardiac EP compared to sodium pentobarbital or isoflurane. Meanwhile, compared to normal body temperature (97-99 F), low body temperature (92-94 F) prolonged most cardiac EP parameters, while high body temperature (102-104 F) had little effect. Heart rate was a sensitive indicator of changes in body temperature. Significant differences were observed in specialized conduction system properties among the mouse strains studied (FVB, C57, and DBA). Furthermore, atrial electrical remodeling was evidently associated with age, while ventricular electrical properties were virtually unaltered. In comparison with corresponding invasive EP parameters, we found that the QT interval was not a reliable EP index in the mouse.


CONCLUSIONS
Cardiac EP variability may result from differences in experimental techniques including anesthesia and body temperature and from differences in mouse selection including strain and age. The influence of these factors should be considered when characterizing the electrical phenotype of transgenic mice in cardiovascular research.
Section of Cardiology, Department of Medicine, and The DeBakey Heart Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Gregory O
GO
Appleton
Yi
Y
Li
George E
GE
Taffet
Craig J
CJ
Hartley
Lloyd H
LH
Michael
Mark L
ML
Entman
Robert
R
Roberts
Dirar S
DS
Khoury
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004558:Electric Stimulation; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria; D006329:Heart Conduction System / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012737:Sex Factors; D016276:Ventricular Function
D000777:Anesthetics