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.
Gutstein
David E
DE
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
Danik
Stephan B
SB
Sereysky
Jedd B
JB
Morley
Gregory E
GE
Fishman
Glenn I
GI
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