Subdiaphragmatic murine electrophysiological studies: sequential determination of ventricular refractoriness and arrhythmia induction.
Programmed electrical stimulation (PES) is a crucial aspect of the evaluation of the risk of arrhythmias in cardiac patients and provides a powerful tool for understanding the mechanisms of arrhythmia in experimental models. Whereas PES in the mouse is well characterized, the procedures allowing for follow-up studies in the same animal have not been developed. In this report, we describe a novel subdiaphragmatic approach that allows for repeat electrophysiological studies in the mouse. Under inhaled anesthesia, PES was performed in 36 wild-type mice via a stimulating electrode introduced through an epigastric incision and placed directly into the diaphragmatic surface of the heart. The procedure was repeated 7 days later. Ventricular effective refractory periods (VERP) did not change significantly between the initial and follow-up trials. Chronic treatment with amiodarone, however, was associated with a 70% prolongation in VERP from initial to follow-up studies (P < or = 0.001). In addition, PES of a genetically modified strain with sudden cardiac death, the connexin43 conditional knockout mouse consistently induced lethal polymorphic ventricular tachycardia. Thus sequential PES in mice is feasible with the use of a subdiaphragmatic approach, yields reproducible VERP values, and can be used to follow pharmacologically induced changes in VERP and identify mice at risk of lethal ventricular arrhythmias.
Department of Medicine, Division of Cardiology, New York University School of Medicine, VA Harbor Medical Center, 423 E. 23rd Street, 6 West-6005BW, New York, NY 10010, USA. david.gutstein@med.nyu.edu
David E
DE
Gutstein
Stephan B
SB
Danik
Jedd B
JB
Sereysky
Gregory E
GE
Morley
Glenn I
GI
Fishman
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D018031:Connexin 43 / Q000235:genetics; D016757:Death, Sudden, Cardiac; D003964:Diaphragm; D004558:Electric Stimulation / Q000379:methods*; D004562:Electrocardiography; D006321:Heart / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D010138:Pacemaker, Artificial; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012307:Risk Factors; D016276:Ventricular Function
D018031:Connexin 43