Academic journal article Indian Journal of Psychiatry

Effects of Electrical Stimulus Composition on Cardiac Electrophysiology in a Rodent Model of Electroconvulsive Therapy

Academic journal article Indian Journal of Psychiatry

Effects of Electrical Stimulus Composition on Cardiac Electrophysiology in a Rodent Model of Electroconvulsive Therapy

Article excerpt

Byline: Nagendra. Singh, T. Sathyaprabha, Jagadisha. Thirthalli, Chittaranjan. Andrade

Background: No electroconvulsive therapy (ECT) study on humans or in animal models has so far examined whether differently composed electrical stimuli exert different cardiac electrophysiological effects at constant electrical dose. The subject is important because cardiac electrophysiological changes may provide indirect information about ECT seizure quality as modulated by stimulus composition. Materials and Methods: Adult female Wistar rats (n = 20/group) received fixed, moderately suprathreshold (18 mC) electrical stimuli. This stimulus in each of eight groups was formed by varying pulse amplitude, pulse width, pulse frequency, and stimulus duration. The electrocardiogram was recorded, and time and frequency domain variables were examined in 30 s epochs in preictal (30 s before electroconvulsive shock [ECS]), early postictal (starting 15 s after stimulation), and late postictal (5 h after ECS) periods. Alpha for statistical significance was set at P < 0.01 to adjust for multiple hypothesis testing. Results: Cardiac electrophysiological indices in the eight groups did not differ significantly at baseline. At both early and late postictal time points, almost no analysis yielded statistically significant differences between groups for four time domain variables, including heart rate and standard deviation of R-R intervals, and for six frequency domain variables, including low-frequency power, high-frequency power, and total power. Conclusions: Cardiac electrophysiological measures may not be helpful to identify differences in seizure quality that are driven by differences in the composition of electrical stimuli at constant, moderately suprathreshold electrical dose. The generalization of this conclusion to threshold electrical doses and to human contexts requires a study.

Introduction

The importance of electroconvulsive therapy (ECT) stimulus dosing in depressed patients receiving ECT is well known; higher doses, relative to the seizure threshold, are associated with faster and better response, especially when unilateral ECT is administered and such higher doses are also associated with a greater cognitive adverse effect burden.[1],[2],[3],[4],[5] However, a given brief-pulse ECT dose can be constituted in different ways by varying pulse amplitude, pulse width, pulse frequency, and stimulus duration.[6],[7] Are all of these identical doses therapeutically equal? It is unlikely. While clinical data on the subject are unavailable to date, in a preclinical model of ECT, it was observed that a stimulus with a narrow pulse width in combination with a high pulse frequency was best associated with electroencephalographic (EEG) proxies of seizure efficacy.[8]

The pulse amplitude (mA) is the strength of the current in the administered electrical stimulus. Pulse width (ms) is the duration for which the neurons are stimulated during each pulse. Pulse frequency (Hz) is the number of pulses delivered per se cond and indirectly represents the recovery time allowed to the neurons between pulses. Stimulus duration(s) is the time for which the stimulus is passed and includes the total number of times the neurons are stimulated by pulses.

Besides the EEG, peak heart rate and rate pressure product have also been suggested as proxies of ECT seizure adequacy.[9],[10] It is therefore possible that cardiac electrophysiological indices, obtained through analysis of the electrocardiogram (ECG) recorded during and after ECT, may also provide useful proxies of the ECT seizure adequacy. However, do these cardiac electrophysiological indices differ with variations in the ECT dose composition at constant electrical dose? This is presently an unanswered question.

In a study that is the first of its kind in literature, we sought to ascertain whether a moderately suprathreshold dose in a rodent model of ECT, composed in different ways by varying the electrical elements of the stimulus, was associated with differences in cardiac electrophysiological variables in the early and late postictal periods. …

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