Aftereffects of high-intensity DC stimulation on the electromechanical performance of ventricular muscle

Abstract

To clarify the mechanisms underlying cardiac dysfunction after electrical defibrillation, we investigated the effects of direct current field stimulation (10 ms, 1-80 V/cm) on isolated guinea pig papillary muscles. Shocks (S2) > 15 V/cm lowered the plateau height of the S2-induced action potential and inhibited its terminal repolarization. Subsequent responses to basic stimuli (S1, 1.0 Hz) for 1-3 min were characterized by a decrease in the maximum diastolic potential, a shortening of action potential duration, and an increase of the developed tension. With S2 > 30 V/cm, a marked delay in repolarization of the S2-induced action potential was followed by oscillation of membrane potential, resulting in repetitive spontaneous activity and often refractoriness to S1 stimulation. The aftereffects were independent of the phase of S2 application. Most of the aftereffects were preserved in the presence of nifedipine (1 microM) or ryanodine (1 microM). Only sodium channel blockade by tetrodotoxin (10 microM) modified the aftereffects by depressing the generation of spontaneous activity. These findings suggest that strong shocks (> 15 V/cm) will produce abnormal arrhythmogenic responses probably through a transient rupture of sarcolemmal membrane (electroporation) leading to a disturbance of the ionic equilibrium of the myocyte.

Electroporation induced by internal defibrillation shock with and without recovery in intact rabbit hearts

“…Electroporated myocytes have a depolarized diastolic potential (12, 23) and altered action potential morphology (23). However, existing studies characterizing shock-induced cardiac electroporation have several critical limitations.First, while there are many studies of electroporation in single myocytes (9,25,41), strands of myocytes (7,12,13), and in tissue preparations (14,23,40), studies in intact whole hearts have been limited. Because shock-induced electroporation is a heterogeneous phenomenon, the position of the defibrillation electrodes can affect the electric field generated (48), thus altering the pattern of electroporation.…”

“…To begin to address this limitation, our group previously characterized the three-dimensional spatial distribution and extent of electroporation in intact normal and MI hearts (22). In that study, a single shock was delivered under paced conditions through a coil electrode placed in the right ventricle (RV), similar to clinical ICD lead placement.Previous studies have also delivered shocks during sinus rhythm (9,23,25,41) or under paced conditions (7, 12-14, 22, 40), rather than during clinically relevant SVF. While ICDs are able to rapidly detect SVF and deliver a rescue shock, patients still experience short periods of SVF before shock delivery.…”

“…Cardiac studies have shown that electroporation occurs in areas of high potential gradients (14,40,41) and alters the flow of ions across the cell membrane (7,13,25). Electroporated myocytes have a depolarized diastolic potential (12,23) and altered action potential morphology (23). However, existing studies characterizing shock-induced cardiac electroporation have several critical limitations.…”

“…Previous studies have also delivered shocks during sinus rhythm (9,23,25,41) or under paced conditions (7, 12-14, 22, 40), rather than during clinically relevant SVF. While ICDs are able to rapidly detect SVF and deliver a rescue shock, patients still experience short periods of SVF before shock delivery.…”

Atria are more susceptible to electroporation than ventricles: Implications for atrial stunning, shock-induced arrhythmia and defibrillation failure

“…However, despite significant improvement in defibrillation efficacy, which has resulted in a radical reduction of defibrillation thresholds and myocardial damage, there is still extensive clinical and basic electrophysiology data indicating that defibrillation shocks are accompanied by adverse effects: (1) transient ectopy, tachycardia or reinduction of VF (1)(2)(3)(4)(5) and AF;(6) (2) bradycardia, complete heart block and increased pacing thresholds;(4;7;8) (3) atrial and ventricular electrical and mechanical dysfunction (stunning), which is directly related to the strength of shocks. (9)(10)(11)(12)(13)(14)(15)(16)(17) These effects are likely to be associated with shock-induced electroporation which is characterized by the formation of aqueous pores in the cellular lipid matrix.…”