Keeping pace with the mouse heart

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Science Translational Medicine  07 Nov 2018:
Vol. 10, Issue 466, eaav6057
DOI: 10.1126/scitranslmed.aav6057


A miniaturized and programmable pacemaker for mice demonstrates the feasibility of long-term cardiac pacing to study cardiac arrhythmias and heart failure.

Cardiac pacing represents the primary therapy for bradycardic arrhythmias (slow irregular heartbeat), including sinus node dysfunction and atrioventricular conduction block. Despite life-saving benefit from pacemakers, it is increasingly recognized that prolonged or chronic cardiac pacing may impart deleterious effects on cardiac physiology. For instance, chronic pacing of the right ventricle or frequent ventricular ectopy (premature contractions arising from the ventricle) contributes to the progression of heart failure through reductions in contractile function and pathological remodeling. However, the mechanistic basis for this phenomenon is unknown. Experimentally, cardiac pacing is an essential modality to test the significance of and decipher the mechanism by which genetic variants predispose to arrhythmias.

Until recently, implantable cardiac pacing in mice has not been feasible due to limited battery performance and technical limitations related to device size, suboptimal pacing rates, and short pacing durations. Hulsmans et al. describe the development of a miniaturized, battery-powered, fully implantable, and programmable pacemaker. The device is implanted under the skin and is connected to a pacing lead that is secured to the epicardial surface of either the left atrium or the apex of the left ventricle. By implanting this device into 39 mice, the authors showed the feasibility of cardiac pacing in conscious mice over a four-week duration. Chronic ventricular pacing was sufficient to effectively treat high degree atrioventricular conduction block. The authors further showed that rapid pacing of the left ventricle resulted in a phenotype resembling tachycardia-induced cardiomyopathy, whereas rapid atrial pacing induced atrial fibrillation in conscious mice.

Implantable long-term pacing devices suitable for mice have been a missing essential technology needed to study fundamental mechanisms underlying diseases of the cardiac conduction system and long-term effects of cardiac pacing. The development of this technology provides new and exciting opportunities to finally explore these important questions in a genetically tractable model. Future studies will undoubtedly provide novel insights into the pathogenesis of atrial fibrillation, ventricular tachycardia, and deleterious effects of atrioventricular dyssynchrony, frequent ventricular ectopy, and chronic ventricular pacing.

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