Chronic Atrial and Ventricular Pacing in the Mouse

Area of Science:

• Cardiovascular Physiology
• Experimental Biology
• Medical Device Development

Background:

• Mice are crucial models in experimental biology, but long-term cardiac pacing has been a translational challenge.
• Existing in vivo cardiac stressor models lack the ability to simulate chronic pacing in conscious, mobile animals.
• This study addresses the need for a method to study cardiac pacing effects in a physiologically relevant, awake mouse model.

Purpose of the Study:

• To develop and validate a novel method for chronic cardiac pacing and electrophysiological recording in conscious, mobile mice.
• To investigate the effects of right ventricular pacing-induced electromechanical dyssynchrony on cardiac function and gene expression.
• To explore the potential for resynchronization therapy in reversing pacing-induced cardiac dysfunction.

Main Methods:

• A custom implantable bipolar lead, flexible external conduit, and electrical micro-commutator were developed for continuous pacing and recording.
• Mice underwent cardiac ischemia/reperfusion injury, followed by 4 weeks of right ventricular pacing (dyssynchrony), right atrial pacing (synchrony), or sequential pacing.
• Cardiac function, myocyte function, gene expression heterogeneity, and kinase activity were assessed.

Main Results:

• The developed method achieved continuous pacing for at least 1 month in 77% of implants, with stable atrial and ventricular capture.
• Right ventricular pacing-induced dyssynchrony significantly reduced heart and myocyte function compared to other groups.
• Dyssynchrony increased gene expression heterogeneity and altered metabolic kinase activity in the lateral wall, which was reversed by resynchronization.

Conclusions:

• The novel chronic pacing method in conscious mice provides stable cardiac capture and a platform for studying electromechanical physiology and therapy.
• The comprehensive data on dyssynchrony and resynchronization in ischemic hearts offers significant insights into ischemic heart disease.
• The findings in mice show similarities to canine models, supporting the translational relevance of this mouse model for cardiac research.