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A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse.

ABSTRACT: RATIONALE:Cardiac pacing is a critical technology for the treatment of arrhythmia and heart failure. The impact of specific pacing strategies on myocardial function is an area of intense research and high clinical significance. Mouse models have proven extremely useful for probing mechanisms of heart disease, but there is currently no reliable technology for long-term pacing in the mouse. OBJECTIVE:We sought to develop a device for long-term pacing studies in mice. We evaluated the device for (1) treating third-degree atrioventricular block after macrophage depletion, (2) ventricular pacing-induced cardiomyopathy, and (3) high-rate atrial pacing. METHODS AND RESULTS:We developed a mouse pacemaker by refashioning a 26 mm×6.7 mm clinical device powered by a miniaturized, highly efficient battery. The electrode was fitted with a single flexible lead, and custom software extended the pacing rate to up to 1200 bpm. The wirelessly programmable device was implanted in the dorsal subcutaneous space of 39 mice. The tunneled lead was passed through a left thoracotomy incision and attached to the epicardial surface of the apex (for ventricular pacing) or the left atrium (for atrial pacing). Mice tolerated the implantation and both long-term atrial and ventricular pacing over weeks. We then validated the pacemaker's suitability for the treatment of atrioventricular block after macrophage depletion in Cd11b DTR mice. Ventricular pacing increased the heart rate from 313±59 to 550 bpm ( P<0.05). In addition, we characterized tachypacing-induced cardiomyopathy in mice. Four weeks of ventricular pacing resulted in reduced left ventricular function, fibrosis, and an increased number of cardiac leukocytes and endothelial activation. Finally, we demonstrated the feasibility of chronic atrial pacing at 1200 bpm. CONCLUSIONS:Long-term pacing with a fully implantable, programmable, and battery-powered device enables previously impossible investigations of arrhythmia and heart failure in the mouse.

SUBMITTER: Hulsmans M

PROVIDER: S-EPMC6309285 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse.

Hulsmans Maarten M Aguirre Aaron D AD Bonner Matthew D MD Bapat Aneesh A Cremer Sebastian S Iwamoto Yoshiko Y King Kevin R KR Swirski Filip K FK Milan David J DJ Weissleder Ralph R Nahrendorf Matthias M

Circulation research 20181101 11

<h4>Rationale</h4>Cardiac pacing is a critical technology for the treatment of arrhythmia and heart failure. The impact of specific pacing strategies on myocardial function is an area of intense research and high clinical significance. Mouse models have proven extremely useful for probing mechanisms of heart disease, but there is currently no reliable technology for long-term pacing in the mouse.<h4>Objective</h4>We sought to develop a device for long-term pacing studies in mice. We evaluated th ...[more]

PMID: 30571465

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Project description:ImportancePrior studies investigating the long-term clinical outcomes of patients who have undergone permanent pacemaker implantation after aortic valve replacement reported conflicting results.ObjectiveTo investigate long-term outcomes after primary surgical aortic valve replacement among patients who underwent postoperative permanent pacemaker implantation.Design, setting, and participantsThis cohort study included all patients who underwent surgical aortic valve replacement in Sweden from 1997 to 2018. All patients who underwent primary surgical aortic valve replacement in Sweden and survived the first 30 days after surgical treatment were included. Patients who underwent preoperative permanent pacemaker implantation, concomitant surgical treatment for another valve, or emergency surgical treatment were excluded. Patients who underwent concomitant coronary artery bypass grafting or surgical treatment of the ascending aorta were included. Follow-up data were complete for all patients. Data were analyzed from October through December 2020.ExposuresPatients underwent implantation of a permanent pacemaker or implantable cardioverter defibrillator within 30 days after aortic valve replacement.Main outcomes and measuresThe primary outcome was all-cause mortality.ResultsAmong 24 983 patients who underwent surgical aortic valve replacement, 849 patients (3.4%) underwent permanent pacemaker implantation within 30 days after surgical treatment and 24 134 patients (96.6%) did not receive pacemakers in that time. The mean (SD) age of the total study population was 69.7 (10.8) years, and 9209 patients were women (36.9%). The mean (SD) and maximum follow-up periods were 7.3 (5.0) years and 22.0 years, respectively. At 10 years and 20 years after surgical treatment, the Kaplan-Meier estimated survival rates were 52.8% and 18.0% in the pacemaker group, respectively, and 57.5% and 19.6% in the nonpacemaker group, respectively. All-cause mortality was statistically significantly increased in the pacemaker group compared with the nonpacemaker group (hazard ratio [HR], 1.14; 95% CI, 1.01-1.29; P = .03), and so was risk of heart failure hospitalization (HR, 1.58; 95% CI, 1.31-1.89; P < .001). No statistically significant increase was found in the risk of endocarditis in the pacemaker group.Conclusions and relevanceThis study found that there were increased risks of all-cause mortality and heart failure hospitalization among patients who underwent permanent pacemaker implantation after surgical aortic valve replacement, suggesting that these risks are important considerations, especially in an era when transcatheter aortic valve replacement is used in younger patients at lower risk of adverse surgical outcomes. These findings further suggest that future research should investigate how to avoid permanent pacemaker dependency after surgical and transcatheter aortic valve replacement.

Dataset Information

A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse.

Publications

A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse.

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