Characterization of Shock‐Induced Action Potential Extension During Acute Regional Ischemia in Rabbit Hearts

Knisley, Stephen B.; Holley, Loraine K.

doi:10.1111/j.1540-8167.1995.tb00354.x

Cited by 12 publications

(10 citation statements)

References 27 publications

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“…These data illustrate that shock-induced depolarization in normoxia extends the APD, whereas in acute ischemia, the APD is either shortened or unchanged. This is consistent with previous observations of shock effects in normoxia (40) and acute ischemia (23).…”

Section: Resultssupporting

confidence: 94%

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Effect of acute global ischemia on the upper limit of vulnerability: a simulation study

Rodríguez

Tice²,

Eason³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Effect of acute global ischemia on the upper limit of vulnerability: a simulation study. Am J Physiol Heart Circ Physiol 286: H2078 -H2088, 2004. First published January 29, 2004 10.1152/ajpheart.01175.2003The goal of this modeling research is to provide mechanistic insight into the effect of altered membrane kinetics associated with 5-12 min of acute global ischemia on the upper limit of cardiac vulnerability (ULV) to electric shocks. We simulate electrical activity in a finiteelement bidomain model of a 4-mm-thick slice through the canine ventricles that incorporates realistic geometry and fiber architecture. Global acute ischemia is represented by changes in membrane dynamics due to hyperkalemia, acidosis, and hypoxia. Two stages of acute ischemia are simulated corresponding to 5-7 min (stage 1) and 10 -12 min (stage 2) after the onset of ischemia. Monophasic shocks are delivered in normoxia and ischemia over a range of coupling intervals, and their outcomes are examined to determine the highest shock strength that resulted in induction of reentrant arrhythmia. Our results demonstrate that acute ischemia stage 1 results in ULV reduction to 0.8A from its normoxic value of 1.4A. In contrast, no arrhythmia is induced regardless of shock strength in acute ischemia stage 2. An investigation of mechanisms underlying this behavior revealed that decreased postshock refractoriness resulting mainly from 1) ischemic electrophysiological substrate and 2) decrease in the extent of areas positively-polarized by the shock is responsible for the change in ULV during stage 1. In contrast, conduction failure is the main cause for the lack of vulnerability in acute ischemia stage 2. The insight provided by this study furthers our understanding of mechanisms by which acute ischemia-induced changes at the ionic level modulate cardiac vulnerability to electric shocks. ionic channels; computer simulations; arrhythmias ELECTRICAL DEFIBRILLATION is recognized as the most effective therapy against the malignant arrhythmias that lead to sudden cardiac death. However, although the majority of the patients that undergo defibrillation typically suffer from some form of coronary disease, little is known about the effect of acute ischemia on defibrillation efficacy. Experimental studies provide conflicting evidence: some report an increase in defibrillation threshold (DFT) (3,29,38,43), whereas others find no change (5,20,22,32) or even a decrease (2) in DFT during acute ischemia.Numerous studies (5,7,18) have demonstrated that the DFT is strongly linked to the upper limit of vulnerability (ULV) of cardiac tissue to electric shocks. Much research has focused on investigating the mechanisms of cardiac vulnerability in an attempt to better understand how failed defibrillation shocks reinitiate cardiac arrhythmias. During the past decade, experiments using optical mapping techniques (8,12,13,46) and computer simulation studies (25,30,37,41) have significantly improved the understanding of the mechanisms of shockinduced arrhythmogenesis, cul...

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Section: Resultssupporting

confidence: 94%

“…Indeed, as a result of ischemia stage 1, first, a smaller amount of tissue experiences shock-induced depolarization and thus APD extension, and second, the value of this APD extension, ⌬APD 90 , is reduced throughout the preparation. The latter finding is consistent with the experimental results of Knisley and Holley (23).…”

Section: Discussionsupporting

confidence: 93%

Effect of acute global ischemia on the upper limit of vulnerability: a simulation study

Rodríguez

Tice²,

Eason³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…Motion blockers were avoided because they might prevent alternans from being observed. Two laboratories have used di-4-ANEPPS to study defibrillation mechanisms in ischemic hearts treated with DAM (4,13,15). Ischemia still Fig.…”

Section: Discussionmentioning

confidence: 99%

“…2 so that the borders of the propagating waveform are not as sharply defined, and the intensity of the fluorescence change during the upstroke is less. This reduction in signal quality is partly due to the addition of blood but may also be due to the deterioration in the relative fluroescence signal, which is known to occur when di-4-ANEPPS is used in ischemic hearts (15).…”

Section: Action Potential Propagation Under Control Conditions and Dumentioning

confidence: 99%

“…Fluorescence imaging has been used to map Ca 2ϩ transient alternans during ischemia in the blood-perfused rabbit heart (30), and marked spatial heterogeneity was found. Optical methods have also been used to study the mechanism of electrical defibrillation in the presence and absence of ischemia in hearts taken from small mammals (4,13,15). For these studies, fully intact hearts were used, which were stained with di-4-ANEPPS and treated with the pharmacological motion blocker diacetyl monoxime (DAM).…”

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confidence: 99%

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Spatial heterogeneity of action potential alternans during global ischemia in the rabbit heart

Qian¹,

Sung²,

Lin³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Qian, You-Wen, Ruey J. Sung, Shien-Fong Lin, Rose Province, and William T Clusin. Spatial heterogeneity of action potential alternans during global ischemia in the rabbit heart. Am J Physiol Heart Circ Physiol 285: H2722-H2733, 2003. First published August 7, 2003 10.1152/ajpheart. 00369.2003.-Cardiac ischemia causes beat-to-beat fluctuation in action potential duration (APD) alternans, which leads to T wave alternans and arrhythmias. Occurrence of APD alternans that is out of phase at two sites is especially important, but most APD alternans studies have involved rapid pacing of normal myocardium rather than ischemia. To determine the spatial features of APD alternans during ischemia, blood-perfused rabbit hearts were stained with 4-{␤-[2(di-n-butylamino)-6-napthyl]vinyl}pyridinium (di-4-ANEPPS) and imaged with a high-resolution camera. Hearts were perfused with oxygenated Tyrode solution at 37°C for staining and then switched to a 50:50% blood/Tyrode mixture. Hearts were paced from the right ventricle at 3/s, and made ischemic by stopping flow for 6 min. Images of 10,000 pixels were obtained at 300 frames/s. Motion artifact was controlled by immobilization and by manual selection of undistorted single-pixel records. Upstroke propagation and conduction isochrones were displayed by computerized image processing. APD alternans was demonstrated in six of seven hearts, and was out of phase in different regions of the image in three hearts. The largest spatial variation in the onset of depolarization to 50% repolarization (APD50) was 155%. This caused beat-to-beat reversal of repolarization. An alternans map could be constructed for well-immobilized portions of the image. There were discrete regions of APD alternans separated by a boundary, as occurs with intracellular Ca 2ϩ concentration alternans. Pixels as close together as 1.1 mm showed an APD alternans that was out of phase. The out-ofphase APD alternans was not due to conduction alternans, as shown by upstroke intervals and conduction isochrones. This contrasts with rapid pacing, where a causal relationship appears to exist. These new observations suggest distinct mechanisms for the genesis of arrhythmias during ischemia.4-{␤-[2(di-n-butylamino)-6-napthyl]vinyl}pyridinium; myocardium; fluorescence imaging; arrhythmias T WAVE ALTERNANS precedes lethal ventricular arrhythmias in experimental animals and also in humans (34). T wave alternans occurs reliably during coronary artery occlusion in large in vivo hearts, and is known to closely precede the onset of ventricular fibrillation (VF)

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A Two-Dimensional Simulation of the Effects of Late Stimulation on a Cardiac Action Potential

Barach

1996

Computers and Biomedical Research

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Characterization of Shock‐Induced Action Potential Extension During Acute Regional Ischemia in Rabbit Hearts

Cited by 12 publications

References 27 publications

Effect of acute global ischemia on the upper limit of vulnerability: a simulation study

Effect of acute global ischemia on the upper limit of vulnerability: a simulation study

Spatial heterogeneity of action potential alternans during global ischemia in the rabbit heart

A Two-Dimensional Simulation of the Effects of Late Stimulation on a Cardiac Action Potential

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