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

Abstract

Wang YT, Efimov IR, Cheng Y. Electroporation induced by internal defibrillation shock with and without recovery in intact rabbit hearts. Am J Physiol Heart Circ Physiol 303: H439 -H449, 2012. First published June 22, 2012; doi:10.1152/ajpheart.01121.2011.-Defibrillation shocks from implantable cardioverter defibrillators can be lifesaving but can also damage cardiac tissues via electroporation. This study characterizes the spatial distribution and extent of defibrillation shock-induced electroporation with and without a 45-min postshock period for cell membranes to recover. Langendorff-perfused rabbit hearts (n ϭ 31) with and without a chronic left ventricular (LV) myocardial infarction (MI) were studied. Mean defibrillation threshold (DFT) was determined to be 161.4 Ϯ 17.1 V and 1.65 Ϯ 0.44 J in MI hearts for internally delivered 8-ms monophasic truncated exponential (MTE) shocks during sustained ventricular fibrillation (Ͼ20 s, SVF). A single 300-V MTE shock (twice determined DFT voltage) was used to terminate SVF. Shock-induced electroporation was assessed by propidium iodide (PI) uptake. Ventricular PI staining was quantified by fluorescent imaging. Histological analysis was performed using Masson's Trichrome staining. Results showed PI staining concentrated near the shock electrode in all hearts. Without recovery, PI staining was similar between normal and MI groups around the shock electrode and over the whole ventricles. However, MI hearts had greater total PI uptake in anterior (P Ͻ 0.01) and posterior (P Ͻ 0.01) LV epicardial regions. Postrecovery, PI staining was reduced substantially, but residual staining remained significant with similar spacial distributions. PI staining under SVF was similar to previously studied paced hearts. In conclusion, electroporation was spatially correlated with the active region of the shock electrode. Additional electroporation occurred in the LV epicardium of MI hearts, in the infarct border zone. Recovery of membrane integrity postelectroporation is likely a prolonged process. Short periods of SVF did not affect electroporation injury. membrane recovery; myocardial infarction; propidium iodide; sustained ventricular fibrillation DEFIBRILLATION IS THE MOST effective and immediate treatment for sustained ventricular fibrillation (SVF), a major cause of sudden cardiac death (SCD) (30). However, while life-saving, defibrillation has adverse effects. These include impaired myocardial contraction and relaxation (50), decreased cardiac output (36) and cardiac index (46), increased pacing threshold (49), and permanent tissue damage (43). This injury may increase the risk of developing heart failure (HF) or exacerbate its symptoms (6,16,44). With the increasing use of implantable cardioverter defibrillators (ICDs) to prevent SCD (28), it is increasingly important to understand the deleterious effects of defibrillation therapy.Electroporation, the disruption of cell membranes by an electric shock, may play a role in these adverse effects. Cardiac studies have shown that electrop...

Excitation of murine cardiac myocytes by nanosecond pulsed electric field

“…49,50 The presence of electroporation usually raises concerns related to its probable complications, like However, findings of the present study demonstrate that AP generation in cardiomyocytes was primarily due to electroporation, which has been also found in hearts undergoing conventional electric shocks of defibrillation intensity.…”

“…However, findings of the present study demonstrate that AP generation in cardiomyocytes was primarily due to electroporation, which has been also found in hearts undergoing conventional electric shocks of defibrillation intensity. 49,50 The presence of electroporation usually raises concerns related to its probable complications, like | 399 nsPEF caused Ca 2+ entry, associated with SSD, which eventually culminated in an AP. This Ca 2+ entry could bypass voltage-gated calcium channels, although the sodium-calcium exchanger and L-type calcium currents both contributed to the SSD.…”

Multiple nanosecond electric pulses increase the number but not the size of long-lived nanopores in the cell membrane

“…Intense nsEP treatments make Pr uptake easily detectable [12,13,18,26], although it remains orders of magnitude weaker than in dead or chemically permeabilized cells. The primary Pr influx through nsEP-opened pores should also be clearly distinguished from a downstream, massive, delayed Pr entry due to membrane rupture in swollen cells [36,37], or due to Ca 2+ -mediated secondary pore opening or enlargement [38].…”

Molecular mechanisms of heart failure progression associated with implantable cardioverter‐defibrillator shocks for ventricular tachyarrhythmias

“…However, this is unlikely because of conflicting observations that electroporation caused by the shock occurs at limited regions. Wang et al examined the spatial distribution and extent of electroporation by assessing propidium iodide uptake in normal and infarcted rabbit hearts subjected to a clinically relevant internal shock for sustained VF [25]. The majority of propidium iodide staining was observed near the shock electrode positioned at the right ventricular apex.…”