Mechanics involved in in the depression contractile and injury of cardiac myocytes submitted to the high intensity electric fields

Author(s)

Pedro Xavier de Oliveira

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia Elétrica e de Computação
• Defense date: 2008-04-16

Examining board members

José Wilson Magalhães Bassani; Airton Ramos; Reinaldo Wilson Vieira; Alberto Paes Gomes; Wilson Nadruz Junior; Eduardo Tavares Costa; José Antenor Pomilio; Vera Lúcia da Silveira Nantes Button

• Advisor: Rosana Almada Bassani; José Wilson Magalhães Bassani

Abstract

Electric defibrillation is currently the treatment able to reverse ventricular fibrillation. However, cardiac stimulation with high-intensity electric fields may cause injury to myocardial cells, thus impairing cardiac contractility. In this study, the effects of highintensity electric fields (E) on isolated rat ventricular myocytes were analyzed. The maximum value of field-induced extracellular potential (Ve-max) was estimated using an electromagnetic model. Our main results were: a) Application of high-intensity E causes sustained increase in cytosolic [Ca2+] ([Ca2+]i) and marked cell contracture, and both effects depend on the presence of extracellular Ca2+; for E> 50 V/cm, these responses are irreversible and lethal injury develops; b) sarcoplasmic reticulum, mitochondria, Na+-Ca2+ exchanger and sarcolemmal L-type Ca2+ channels do not seem to contribute significantly to such effects; c) when shocks were applied to cells depolarized by high extracellular [K+], Ve-max was increased by an extent that was close to the value of the resting transmembrane potential (Vm ~-85 mV), which indicates that Ve-max may be considered a reasonable estimation of the maximum variation of Vm during the shock; d) increase in cell resistance to the lethal effect of E, assessed as the value of E associated to 50% probability of lethality (EL50), was observed during application of biphasic stimuli with the same pulse energy, during ß-adrenergic receptor stimulation, and in myocytes isolated from rats in which stress was induced by repeated immobilization and footshock. It may be concluded that: a) The sustained increase in [Ca2+]i is probably due to Ca2+ influx through hydrophilic membrane pores generated during application of high-intensity E (electroporation); b) the better defibrillation results described in the literature with biphasic shock may be due, at least partly, to the lesser ability of this waveform to cause lethal injury; c) both in vitro ß-adrenergic stimulation and the stress condition in vivo appear to exert a protective effect against the lethal effect of E. We expect that the present results may contribute to the development of safer procedures for both pacemaker and defibrillatory field stimulation of the myocardium (AU)