Regional electromechanical alternans in anesthetized pig hearts: modulation by mechanoelectric feedback

Murphy, C.F.; Lab, Max J.; Horner, S M; Dick, D J; Harrison, F G

doi:10.1152/ajpheart.1994.267.5.h1726

Cited by 18 publications

(13 citation statements)

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“…It appears that the electrical phenomenon is the consequence rather than the cause of the contractile alternans, based on several observations that suppression of the contractile alternans also suppressed the electrical alternans (reviewed in 1 ). This could be due to a direct mechanoelectrical feedback 7 on the other hand, shows that at a given level of SR Ca 2ϩ , this relation becomes suddenly very steep. It is the steepness of this relation that underlies the alternans behavior and the depletion/repletion cycle of the SR.…”

Section: Clinical Relevance Of T-wave Alternans and Link To Cellular mentioning

confidence: 96%

Understanding Cardiac Alternans

Sipido

2004

Circulation Research

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Section: Clinical Relevance Of T-wave Alternans and Link To Cellular mentioning

confidence: 96%

Understanding Cardiac Alternans

Sipido

2004

Circulation Research

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“…For example, Lee et al (1988) have shown electrical-mechanical discordance (short APD associated with large calcium transient) in ischemic hearts. Murphy et al (1994) have also shown electrical-mechanical discordant alternans, but in normal Landrace pigs that were paced rapidly.…”

Section: Voltage and Calcium Couplingmentioning

confidence: 97%

“…Since electrical and mechanical alternans are frequently observed concurrently at the cellular and whole heart level, (Lu et al, 1968;Murphy et al, 1994;Pruvot et al, 2004) it is likely that calcium, an important regulator of cellular contraction and electrophysiology, is involved. Shown in Figure 3 is a simplified diagram of cellular calcium regulation.…”

Section: Intracellular Calcium Regulationmentioning

confidence: 99%

Cellular mechanisms of arrhythmogenic cardiac alternans

Laurita

Rosenbaum

2008

Progress in Biophysics and Molecular Biology

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Mechanical dysfunction remains as one of the best predictors of sudden cardiac death (SCD), but despite this close association the causal relationships between electrical instability and mechanical dysfunction are not fully understood. (Bigger et al., 1984;Buxton et al., 1984) Even though the effects of electrical instability on mechanical dysfunction of the heart is well appreciated and relatively clear, the reverse effects that mechanical dysfunction have electrical instability, or mechano-electrical feedback (MEF), are not. (Kohl et al., 2006;Lab, 1996) Stretch activated channels, for example, are one way mechanical activity can directly influence electrical activity at the cellular level under physiologic and pathophysiological conditions. (Hu et al., 1997) Alternatively, intracellular calcium, which regulates mechanical contraction, can significantly influence electrical function of the heart as well. The mechanisms by which intracellular calcium governs electrical instability of the heart is the main focus of this manuscript. Traditionally, calcium mediated arrhythmogenesis is associated with delayed after depolarizations and abnormal impulse formation. (Katra et al., 2007;Liu et al., 2006;Rosen, 1985;Ter Keurs et al., 2006;Wehrens et al., 2003) However, in this manuscript we focus on how cardiac alternans, a mechanisms of reentrant excitation, is another significant way mechanical dysfunction and arrhythmogenesis are causally related.Cardiac alternans can refer to either mechanical (contractile) or electrical (repolarization) oscillations that occur on an every other beat basis. Cardiac alternans has been recognized for more than 100 years. Shown in Figure 1 (Panel A) is a very early record of arterial pressure measured during a steady state heart rate, where pulse magnitude alternates on every other beat (arrows). (Traube, 1872) At this time, the ECG had not been invented; however, soon after its introduction electrical alternans was reported as well. Shown in Panel B (Figure 1) is an early example of electrical alternans as evidenced by oscillations of the ECG T-wave (arrows) and QRS. (Lewis, 1910) Soon after cardiac alternans was first reported, it was associated with a poor prognosis. (Windle, 1913) Surprisingly, at this same time several important characteristics of cardiac alternans were observed, such as alternans occurring in a structurally normal heart and appearing at faster heart rates. Subsequently, Twave alternans was more directly related to coronary artery occlusion and shown to be highly reproducible. (Hellerstein et al., 1950)

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“…For example, measurements were made in a nonworking heart, whereas mechanical loading can potentially influence electrical alternans via mechanoelectrical feedback mechanisms. 7,9,10,17 Also, some evidence suggests that T-wave alternans is dependent on sympathetic stimulation, 5 which is absent in isolated heart preparations. However, sympathetic stimulation does not appear to influence the amplitude of T-wave alternans in patients with structural heart disease and ventricular arrhythmias.…”

Section: Experimental Model Of Steady-state T-wave Alternansmentioning

confidence: 99%

“…The second hypothesis states that T-wave alternans is caused primarily by alternations in repolarization of the action potential, which may give rise to secondary propagation alternans. 11,12,[15][16][17][18] However, the regional membrane changes that underlie the development of T-wave alternans in the intact heart and the possible role such changes play in the mechanism of ventricular arrhythmias are poorly understood because (1) conventional recording techniques cannot be used to monitor cellular membrane potential with sufficient spatial resolution during the development of ECG T-wave alternans and (2) experimental studies have focused on transient alternans during an abrupt change in cycle length (CL) 9,19,20 or alternans during myocardial ischemia, 8,10 -12,21 whereas the majority of patients at risk for sudden cardiac death exhibit T-wave alternans at a relatively constant heart rate (HR) and in the absence of acute ischemia. 13 Therefore, we used the technique of high-resolution optical action potential mapping in an intact heart model of pacing-induced T-wave alternans to determine if T-wave alternans is causally linked to the mechanism of reentry.…”

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confidence: 99%

Mechanism Linking T-Wave Alternans to the Genesis of Cardiac Fibrillation

et al. 1999

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Background-Although T-wave alternans has been closely associated with vulnerability to ventricular arrhythmias, the cellular processes underlying T-wave alternans and their role, if any, in the mechanism of reentry remain unclear. Methods and Results-T-wave alternans on the surface ECG was elicited in 8 Langendorff-perfused guinea pig hearts during fixed-rate pacing while action potentials were recorded simultaneously from 128 epicardial sites with voltage-sensitive dyes. Alternans of the repolarization phase of the action potential was observed above a critical threshold heart rate (HR) (209Ϯ46 bpm) that was significantly lower (by 57Ϯ36 bpm) than the HR threshold for alternation of action potential depolarization. The magnitude (range, 2.7 to 47.0 mV) and HR threshold (range, 171 to 272 bpm) of repolarization alternans varied substantially between cells across the epicardial surface. T-wave alternans on the surface ECG was explained primarily by beat-to-beat alternation in the time course of cellular repolarization. Above a critical HR, membrane repolarization alternated with the opposite phase between neighboring cells (ie, discordant alternans), creating large spatial gradients of repolarization. In the presence of discordant alternans, a small acceleration of pacing cycle length produced a characteristic sequence of events: (1) unidirectional block of an impulse propagating against steep gradients of repolarization, (2) reentrant propagation, and (3) the initiation of ventricular fibrillation. Conclusions-Repolarization alternans at the level of the single cell accounts for T-wave alternans on the surface ECG.Discordant alternans produces spatial gradients of repolarization of sufficient magnitude to cause unidirectional block and reentrant ventricular fibrillation. These data establish a mechanism linking T-wave alternans of the ECG to the pathogenesis of sudden cardiac death. (Circulation. 1999;99:1385-1394.)

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Regional electromechanical alternans in anesthetized pig hearts: modulation by mechanoelectric feedback

Cited by 18 publications

References 0 publications

Understanding Cardiac Alternans

Understanding Cardiac Alternans

Cellular mechanisms of arrhythmogenic cardiac alternans

Mechanism Linking T-Wave Alternans to the Genesis of Cardiac Fibrillation

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