Programmed electrical stimulation provides the ability to determine conduction properties of the heart, and the possibility to induce and terminate cardiac arrhythmias using various pacing protocols. Using a transvenous catheter, intracardiac electrogram recordings can be obtained in mice following programmed electrical stimulation protocols to identify arrhythmogenic substrates.
Part 1. Surgical preparation
Part 2. Cannulation and insertion of EP catheter into right atrium and ventricle
Part 3. Programmed Electrical Stimulation
Part 4. Removal of Catheter
Representative Results
Surface ECG and intracardiac electrograms are recorded simultaneously throughout the in vivo electrophysiology study, and are reviewed in detail following the completion of all protocols. The baseline electrophysiological parameters include PR interval, PQ interval, QRS duration, QT intervals, and QRS morphology. These parameters can be measured manually, or automatically using the data acquisition software IOX-2 or ECG-AUTO (Emka Technologies, VA, USA).
The SNRT, AERP, and AVNERP provide information regarding the sinus node “pacemaker” function, atrial, and AV nodal conduction properties, respectively. Examples of pacing-induced episodes of atrial fibrillation can be found in the paper by Chelu et al.4
Figure 1. Illustration of intracardiac catheterization for electrophysiology studies in mice. A. Right internal jugular vein is isolated and cannulated. The distal end of vein is tied off once proper catheter position is achieved. B. The mouse is placed in a supine position for this procedure. C. Cartoon depicting the intracardiac position of catheter. Pair of electrodes are positioned at the level of the apex of the right ventricle, the base of the right ventricle, the atrioventricular node, and the right atrium, respectively. D. Close-up of the 1.1F octapolar catheter. Figure modified from Mathur et al. with permission of Circ Arrhtyhm Electrophys 5.
Figure 2. Representative Surface ECG and Intracardiac Electrograms in a Mouse. (A) Surface ECG in lead II configuration showing regular sinus rhythm with a frequency of 540 beats per minute. (B-E) Bipolar intracardiac electrogram recordings at the level of the right atrium (B), atrioventricular node (C), and base of the right ventricle (D), and the apex of the right ventricle (E), respectively. Note that the intracardiac A-wave in panel B corresponds to the P-wave on the surface ECG. The V-wave on the ventricular electrogram corresponds to the QRS wave on the surface ECG.
Figure 3. Representative surface ECG and intracardiac electrograms in a mouse that developed atrial fibrillation after atrial burst pacing.
During cardiac catheterization, extensive bleeding during catheterization could increase the heart rate due to hypovolemia. In this case, an intraperitoneal injection of sterile saline (0.3 1.0 mL) could normalize filling pressure and reduce hemodynamic stress in the mouse.
Exposure to isoflurane longer than 2 hours, or higher concentrations of isoflurane (>2 %) could suppress cardiac and respiratory functions in the mouse. Therefore, it is recommended that all studies be completed in less than 2 hours. Moreover, it is essential that the body temperature is always maintained within the normal range 37.0 ± 1.0°C. Both hypothermia and hyperthermia will affect the heart rhythm and the potential presence of an arrhythmogenic substrate.
Each experiment should begin by determining atrial capture thresholds. In the case of atrial pacing, atrial threshold, SNRT, AERP, and AVNERP should be determined to assess whether the conduction properties of the sinus node, AV node, and atrial tissue are normal.
X.H.T.W. is a W.M. Keck Foundation Distinguished Young Scholar in Medical Research, and is also supported by NIH/NHLBI grants R01-HL089598 and R01HL091947, and Muscular Dystrophy Association grant #69238. This work is also supported in part by the Fondation Leducq Alliance for CaMKII Signalling in Heart. N.L. is the recipient of the 2009-2010 Michel Mirowski International Fellowship in Cardiac Pacing and Electrophysiology from Heart Rhythm Society and 2009-2012 American Heart Association Postdoc Fellowship.