Greater Cardiac Cell Excitation Efficiency With Rapidly Switching Multidirectional Electrical Stimulation

Abstract

Electric field (E) stimulation is widely used in experiments with myocardial preparations and in the clinical setting (e.g., defibrillation). As a rule, stimuli are applied in a single direction, which limits excitatory cell recruitment because myocytes are disposed in different directions and their sensitivity to E depends on the stimulus orientation with respect to the cell major axis. Here, we propose a stimulatory approach, namely rapidly switching multidirectional stimulation (RSMS), in which stimuli are delivered in three directions within the electric refractory period. In populations of randomly oriented isolated rat cardiomyocytes, RSMS doubled the percentage of cells excited by near-threshold E (P < 0.001), which was more than the increase in recruitment in a single direction achieved by doubling E intensity. This effect was similar for monophasic and biphasic pulses, but for the latter, a given percent recruitment was obtained with 20-30% lower E intensity ( P < 0.01), so that RSMS with biphasic pulses allowed at least 60% reduction of E intensity for recruitment of >70% of the cells. RSMS can be applied to improve stimulation efficiency in experiments with isolated cardiac myocytes, and may be a promising alternative for decreasing shock intensity requirements for cardioversion and defibrillation.

System for open-chest, multidirectional electrical defibrillation

“…Thus, multidirectional stimulation should be able to promote electrical recruitment of cells that might remain unexcited by unidirectional stimulation, thus allowing effective stimulation with lower and safer field intensities. This proposal was confirmed for both near-excitation threshold and high-intensity field stimulation of isolated cardiac myocytes (Fonseca et al, 2013) and of the whole heart in vivo (Viana et al, 2014;present study).…”

“…SE 0.5 : estimated shock energy associated with a probability of successful defibrillation equal to 0.5 (mean ± standard error), obtained from the defibrillation curves shown in Figure 7 0.000 3.81 ± 0.05 (9) 0.000 2.98 ± 0.01 (9) <0.001 defibrillatory shock. This electronic type of switch was chosen to avoid prolonging of the total discharge duration, which is observed when relays are used for switching among outputs (Fonseca et al, 2013). The results of the bench and in vivo tests showed that this option resulted in reproducible discharge duration, in agreement with the preset value.…”

“…Even though temporal superposition should further enhance excitatory recruitment, it should also increase the damaging potential of high-intensity field stimulation, which may result in failure of defibrillation due to arrhythmia reinduction and/or myocardial injury. Fonseca et al (2013) identified two mechanisms involved in the enhanced electrical recruitment of cardiac myocytes during rapidly-switching, sequential application of electrical field in different directions. One of them is direction-dependent, probably due to the induction of threshold depolarization in a greater number of cells, as explained earlier.…”

“…The present instrument, developed at the Center for Biomedical Engineering of the University of Campinas (CEB/UNICAMP), was based on the combination of a switching circuit that allows the output to be changed among different pairs of electrodes (Fonseca et al, 2013), and a capacitive pulse generator that delivers monophasic, truncated exponential voltage pulses (American National Standards Institute…, 1996;Associação Brasileira de Normas Técnicas…, 2005). In its present version, the instrument can deliver sequential shocks up to 3 outputs (pairs of electrodes).…”

“…A problem of the practical application of this approach to defibrillation is that myocytes are disposed in several directions in the whole heart (Smerup et al, 2009). Nevertheless, using randomly-oriented isolated ventricular myocytes as an experimental model for heterogeneous cell spatial orientation, Fonseca et al (2013) showed that rapidly switching stimuli among 3 directions was able to more than double the percentage of cells excited by near-threshold stimulus amplitude.…”