AJP - Heart 2021

Restoring sinus rhythm

The process of restoring sinus rhythm in the atria has been represented in Figure 1. Our heart tissue consists of many heart cells, each of which undergoes electrical changes. As a reaction to these electrical changes, the heart contracts. Therefore atrial propagation can not only be described as a disorganized contraction of the upper chambers of the heart, but also as disorganized electrical activity in the upper chambers of the heart. As a consequence this means that when we are capable of restoring the electrical activity back to normal, we will also achieve regular contraction of the heart. This restoring of electrical activity can be done by providing a shock to all the cells that resets them, after which sinus rhythm can take over again. This is the principle on which defibrillators are based. These shocks are very painful though, and they leave patients in distress over the next painful shock episode. Our own heart cells however contain the possibility to generate their own electricity. This happens through small pores in the cell membrane called ion channels. It was now our idea to add an extra ion channel to the heart cells that has the same function as a defibrillator. To get this extra ion channel in the heart we need a transporter to get it there, which is accomplished by the viral vector. Once the ion channel is there, it senses arrhythmias and as a reaction to it, produces extra current to defibrillate the heart in a fully biological way.

Implications

Such a fully biological approach for restoring heart rhythm may have unique benefits given its hardware/software free design, and its ambulatory mode of operation. The first-mentioned advantage is that known issues with implantable devices could be circumvented. A second benefit of biological cardioversion is that it may provide a robust and effective way to terminate arrhythmia in those cases where rhythm control is of particular desire, but more traditional methods like drugs and/or ablation fail to accomplish this. As a third benefit, given the ambulatory nature of biological cardioversion, the effective duration of AF could be minimized. This would not only avoid AF-related symptoms and complications but also repetitive hospitalization, anesthesia, and electric shocks for cardioversion.

For these reasons the next step is to move this from a theoretical concept to a practically attainable solution by looking towards possible ion channels that could be modified or adapted to gain the function of a biological defibrillator.

The American Journal of Physiology-Heart and Circulatory Physiology publishes original investigations, reviews and perspectives on the physiology of the heart, vasculature, and lymphatics. These articles include experimental and theoretical studies of cardiovascular function at all levels of organization ranging from the intact and integrative animal and organ function to the cellular, subcellular, and molecular levels. The journal embraces new descriptions of these functions and their control systems, as well as their basis in biochemistry, biophysics, genetics, and cell biology. Preference is given to research that provides significant new mechanistic physiological insights that determine the performance of the normal and abnormal heart and circulation.