The ionic mechanism of reperfusion-induced early afterdepolarizations in feline left ventricular hypertrophy.

Abstract

Left ventricular hypertrophy (LVH) potentiates reperfusionassociated ventricular fibrillation. To study the mechanism responsible, patch-clamp techniques were used to evaluate transmembrane ionic currents during "reperfusion" after a CN --induced metabolic surrogate for ischemia in isolated myocytes from a feline model of experimental LVH. Reperfusion caused the generation of early afterdepolarizations (EADs) from an average take-off potential of -33 mV in LVH cells but not in cells from normal hearts. 10 min after initiating reperfusion of normal cells, action potential duration (APD) at 50% repolarization (APDTO) lengthened from 198±41 to 233±57 ms whereas in LVH cells APDjo lengthened from 262±84 to 349±131 ms (P < 0.05). Among the LVH cells, APDjo lengthening was significantly greater in the cells that had developed EADs. During reperfusion, steady state outward current in the voltage range of the action potential plateau (between -20 and +20 mV) was reduced from the control values in LVH cells but not in normal cells. Reperfusion-related reduction of steady state outward current in LVH cells was abolished under experimental conditions in which L-type Ca2+ current was isolated from other classes of currents whereas it was still observed under the condition in which pure K+ currents could be recorded. Thus, reduction of steady state outward current due to the reduction of outward K+ current over the action potential plateau voltage range appears to be responsible for an excessive prolongation of APD, leading to the development of EADs. (J. Clin. Invest. 1993. 91:1521-1531

Sudden Cardiac Death With Apparently Normal Heart

“…29 Observations in animal models suggest that cardiac myocytes from hypertrophied hearts develop abnormalities of repolarization, which could predispose to fatal arrhythmogenesis. 30 Similarly, it is conceivable that nonspecific interstitial fibrosis could contribute to the initiation of ventricular arrhythmias through a functional reentrant mechanism. 31 The presence of fibrosis in some component of the conduction system in 8 of 9 hearts subjected to a detailed conduction system examination suggests a propensity for bradycardia in some of these patients.…”

Sudden Cardiac Death Caused by Coronary Heart Disease

“…With either stable or unstable plaque conditions, myocardial perfusion variations that create sequences of ischemia and reperfusion initiate regional variations in myocardial cell membrane electrophysiology. 51 These variations contribute a transient substrate for triggered activity and reentry as the basis for initiating arrhythmias.…”

“…52 In the latter, clinical and experimental evidence shows that the reperfusion phase is associated with lengthening of the time course of repolarization in the affected area, equivalent to a regional "long QT" in the ischemic area. 51 This contributes to the generation of triggered activity leading to polymorphic ventricular tachycardia, which in turn may initiate reentrant tachyarrhythmias leading to cardiac arrest. It is likely that transient ischemia and/or reperfusion are common mechanisms by which first coronary events express as SCD.…”

“…En esta última situación, la isquemia es iniciada por la incapacidad de satisfacer las necesidades de flujo bajo una serie específica de condiciones, como un aumento brusco de la demanda de flujo sanguíneo coronario como consecuencia de un acortamiento del periodo de flujo diastólico de forma asociada a la taquicardia. En las condiciones de placa estable o inestable, las variaciones de la perfusión miocárdica que crean secuencias de isquemia y reperfusión inician las variaciones regionales de la electrofisiología de la membrana celular miocárdica 51 . Estas variaciones contribuyen a producir un substrato transitorio para la actividad desencadenada y la reentrada, que es la base del desencadenamiento de las arritmias.…”

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

“…It has been shown that long-term administration of IGF-I regulates the expression of the K ϩ channel in cultured neonatal rat ventricular myocytes (18). Most studies regarding the electrophysiological alterations associated with cardiac hypertrophy were performed on the pressure-overload model, which has been associated with reduction in I to (6,15,16,53) and no change (6,57) or a decrease in I K (13,14,29,30) and I K1 (5,15,37). Interestingly, Brooksby et al (5) have shown that the electrical remodeling related to cardiac hypertrophy was restricted to a decrease in I K1 current density with no difference in the resting potential level of cardiomyocytes from control and spontaneously hypertensive rats.…”