Once cardiac electrical activity is disturbed, such as with sustained arrhythmias, the heart is not capable of self-restoring a normal rhythm. However, according to a new study combining theoretical and experimental assays, a biological detector–effector system involving the expression of a customized ion channel in cardiomyocytes can enable the heart to automatically detect and terminate acute arrhythmias. Studies on these biological self-restoring systems can contribute to the development of arrhythmia management strategies that avoid the need for devices, wires or electric shocks for defibrillation.
The biological self-restoring system developed by the group of Daniël Pijnappels, named the biologically integrated cardiac defibrillator (BioICD), involves the introduction of a new ion channel with specific properties into the sarcolemma of cardiomyocytes. The gating of the ion channel is customized to differentiate between normal rhythm and arrhythmia (based on the detection of high-frequency signals irrespective of the nature and underlying cause of the arrhythmia) and to generate an ionic current for the termination of the detected arrhythmia. First, the investigators validated the BioICD concept in silico using simulations of human cardiomyocyte monolayers and of atria and ventricles. The virtual models that had the BioICD integrated were capable of autodetecting the arrhythmia and restoring sinus rhythm within seconds of arrhythmia initiation without the need of a non-biological factor. Next, the researchers validated the BioICD concept in living cells in vitro. The experimental assays involved the dynamic patch-clamp technique (which allows the introduction of virtual voltage-gated ion channels, such as the BioICD, into excitable cells) and human atrial cardiomyocytes optogenetically modified to express a light-gated ion channel (which enables optical control of excitation rhythm with a light source). The data showed that the same ion channel gating properties used for the computer simulations enabled the detection of arrhythmias and the restoration of cardiac excitation rhythm in the living cells.
these findings provide proof of concept of a fully biological detector–effector system for the regulation of cardiac arrhythmias
Taken together, these findings provide proof of concept of a fully biological detector–effector system for the regulation of cardiac arrhythmias.
Majumder, R. et al. Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating. eLife 9, e55921 (2020)
Niederer, S. A. et al. Computational models in cardiology. Nat. Rev. Cardiol. 16, 100–111 (2020)
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Fernández-Ruiz, I. A fully biological defibrillation system for restoring cardiac rhythm. Nat Rev Cardiol 17, 455 (2020). https://doi.org/10.1038/s41569-020-0411-y