Programmed Electrical Stimulation in Mice

Summary

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.

Abstract

Genetically-modified mice have emerged as a preferable animal model to study the molecular mechanisms underlying conduction abnormalities, atrial and ventricular arrhythmias, and sudden cardiac death.¹ Intracardiac pacing studies can be performed in mice using a 1.1F octapolar catheter inserted into the jugular vein, and advanced into the right atrium and ventricle. Here, we illustrate the steps involved in performing programmed electrical stimulation in mice. Surface ECG and intracardiac electrograms are recorded simultaneously in the atria, atrioventricular junction, and ventricular myocardium, whereas intracardiac pacing of the atrium is performed using an external stimulator. Thus, programmed electrical stimulation in mice provides unique opportunities to explore molecular mechanisms underlying conduction defects and cardiac arrhythmias.

Protocol

Part 1. Surgical preparation

1. In case programmed electrical stimulation experiments are performed as survival surgeries in mice sterile conditions will be necessary. However, the most common type of experiment is terminal in nature, for which regular clear surgical techniques suffice.
2. The mouse is anesthetized using 2% isoflurane in 0.5 L/min 100% O₂.
3. Hair clippers are used to shave the fur from the neckline to mid chest level.
4. The anesthetized mouse is placed in a supine position, with its limbs taped onto ECG electrodes incorporated in a heating board (Indus Instruments, Houston, TX). And the surgica....

Discussion

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 le.......