Abstract
A noninvasive, effective approach for immediate and painless heart pacing would have invaluable implications in several clinical scenarios. Here we present a novel strategy that utilizes the well-known mechano-electric feedback of the heart to evoke cardiac pacing, while relying on magnetic microparticles as leadless mechanical stimulators. We demonstrate that after localizing intravenously-injected magnetic microparticles in the right ventricular cavity using an external electromagnet, the application of magnetic pulses generates mechanical stimulation that provokes ventricular overdrive pacing in the rat heart. This temporary pacing consistently managed to revert drug-induced bradycardia, but could only last up to several seconds in the rat model, most likely due to escape of the particles between the applied pulses using our current experimental setting. In a pig model with open chest, MEF-based pacing was induced by banging magnetic particles and has lasted for a longer time. Due to overheating of the electromagnet, we intentionally terminated the experiments after 2 min. Our results demonstrate for the first time the feasibility of external leadless temporary pacing, using injectable magnetic microparticles that are manipulated by an external electromagnet. This new approach can have important utilities in clinical settings in which immediate and painless control of cardiac rhythm is required.
Highlights
Pacing modalities for electrical stimulation of the heart are fundamental tools in modern cardiac electrophysiology and are used for various clinical purposes[1,2]
The magnetic attraction applied by a given magnet on a magnetic microparticle is proportional to its mass, to the third power of its radius, while the drag force applied by the blood flow is proportional to the radius
The present study is a proof-of-concept, showing the feasibility of a novel and unique approach to induce noninvasive cardiac pacing utilizing injectable magnetic microparticles and low energy magnetic waveforms applied to the chest wall
Summary
Pacing modalities for electrical stimulation of the heart are fundamental tools in modern cardiac electrophysiology and are used for various clinical purposes[1,2]. The typical procedure for either temporary or permanent pacemaker implantation is invasive, takes time and is preferably done under fluoroscopy by skilled personnel This form of therapy encompasses risks of bleeding, infection[6,7,8,9] and thrombosis[8,10] and importantly, is not readily available in cases requiring acute and rapid application of pacing, which can be life-saving in patients suffering from bradycardia and hemodynamic compromise[11]. It should be noted that local pressure as low as 2kPa may provoke MEF-dependent pacing[21], while tissue damage usually starts when the impact energy exceeds ~250kPa22 This gap of over two orders of magnitude gives a large therapeutic window for safe MEF-induced cardiac pacing. We used ex-vivo and in-vivo rat models, followed by proof-of-concept experiments in a pig model, in order to demonstrate the feasibility of our novel approach
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