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Real-Time Closed Loop Diastolic Interval Control Prevents Cardiac Alternans in Isolated Whole Rabbit Hearts

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Abstract

Cardiac alternans, a beat-to-beat alternation in action potential duration (APD), can lead to fatal arrhythmias. During periodic pacing, changes in diastolic interval (DI) depend on subsequent changes in APD, thus enhancing cardiac instabilities through a ‘feedback’ mechanism. Recently, an anti-arrhythmic Constant DI pacing protocol was proposed and shown to be effective in suppressing alternans in 0D and 1D in silico studies. However, previous experimental validation of Constant DI pacing in the heart has been unsuccessful due to the spatio-temporal complexity of 2D cardiac tissue and the technical challenges in its real-time implementation. Here, we developed a novel closed loop system to detect T-waves from real-time ECG data, enabling successful implementation of Constant DI pacing protocol, and performed high-resolution optical mapping experiments on isolated whole rabbit hearts to validate its anti-arrhythmic effects. The results were compared with: (1) Periodic pacing (feedback inherent) and (2) pacing with heart rate variability (HRV) (feedback modulation) introduced by using either Gaussian or Physiological patterns. We observed that Constant DI pacing significantly suppressed alternans in the heart, while maintaining APD spatial dispersion and flattening the slope of the APD restitution curve, compared to traditional Periodic pacing. In addition, introduction of HRV in Periodic pacing failed to prevent cardiac alternans, and was arrhythmogenic.

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Acknowledgments

This study was funded by the National Institute of Health F31HL129544 (to S.W.L.) and R21HL128790 (to E.G.T.), National Science Foundation CAREER PHY-125541 and DCSD 1662250. This work was conducted as a part of the Prediction and Control of Cardiac Alternans Working Group at the National Institute for Mathematical and Biological Synthesis, sponsored by the National Science Foundation through NSF Award #DBI-1300426.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Minnesota, 6-128 Nils Hasselmo Hall, 312 Church St. SE, Minneapolis, MN, 55455, USA

    Kanchan Kulkarni, Steven W. Lee, Ryan Kluck & Elena G. Tolkacheva

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  1. Kanchan Kulkarni
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  2. Steven W. Lee
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  3. Ryan Kluck
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  4. Elena G. Tolkacheva
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Correspondence to Elena G. Tolkacheva.

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Associate Editor Ellen Kuhl oversaw the review of this article.

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Kulkarni, K., Lee, S.W., Kluck, R. et al. Real-Time Closed Loop Diastolic Interval Control Prevents Cardiac Alternans in Isolated Whole Rabbit Hearts. Ann Biomed Eng 46, 555–566 (2018). https://doi.org/10.1007/s10439-018-1981-2

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  • DOI: https://doi.org/10.1007/s10439-018-1981-2

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