Electrical and mechanical alternans in canine myocardium in vivo. Dependence on intracellular calcium cycling.

Hirayama, Yoshiyuki; Saitoh, Hirokazu; Atarashi, Hirotsugu; Hayakawa, Hirokazu

doi:10.1161/01.cir.88.6.2894

Cited by 79 publications

(74 citation statements)

References 29 publications

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“…20,25,26,32 Results from the present study suggest that discordant alternans that arises by the second scenario could be prevented by drugs that increase conduction velocity or reduce range of DI over which conduction velocity varies, even if concordant alternans is not preventable.…”

Section: Discussionmentioning

confidence: 70%

“…[28][29][30] Two recent studies support primacy of APD alternans; activation times were identical from beat to beat. 31,32 Appearance of repolarization alternans at slower heart rate than depolarization alternans 8 also might be interpreted by some that conduction velocity is of lesser importance, although one would naturally expect repolarization (APD) alternans to occur at slower heart rates than depolarization (conduction velocity) alternans in normal cardiac tissue, because of the shorter DI at which conduction velocity varies. However, at the high pacing rates at which discordant alternans is seen, DI typically is small, and effects of conduction velocity cannot be separated from effects of repolarization.…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms for Discordant Alternans

Watanabe

Fenton

Evans

et al. 2001

Cardiovasc electrophysiol

307

360

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Discordant Alternans Mechanism. Introduction: Discordant alternans has the potential to produce larger alternans of the ECG T wave than concordant alternans, but its mechanism is unknown. Methods and Results:We demonstrate by one-and two-dimensional simulation of action potential propagation models that discordant alternans can form spontaneously in spatially homogeneous tissue through one of two mechanisms, due to the interaction of conduction velocity and action potential duration restitution at high pacing frequencies or through the dispersion of diastolic interval produced by ectopic foci. In discordant alternans due to the rst mechanism, the boundaries marking regions of alternans with opposite phase arise far from the stimulus site, move toward the stimulus site, and stabilize. Dynamic splitting of action potential duration restitution curves due to electrotonic coupling plays a crucial role in this stability. Larger tissues and faster pacing rates are conducive to multiple boundaries, and inhomogeneities of tissue properties facilitate or inhibit formation of boundaries.Conclusion: Spatial inhomogeneities of electrical restitution properties are not required to produce discordant alternans.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Mechanisms for Discordant Alternans

Watanabe

Fenton

Evans

et al. 2001

Cardiovasc electrophysiol

307

360

View full text Add to dashboard Cite

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“…That said, the model does not negate the importance of intracellular calcium concentration in determination of myocardial APD. Changes to intracellular calcium concentration affect APD restitution (24) and APD alternans (19,26,43). We conjecture that the calcium concentration determines APD restitution and accommodation and that the two can be measured and modeled decoupled from calcium concentration without consequence because they already encode the calcium concentration information.…”

Section: Modeling Results and Implicationsmentioning

confidence: 94%

Mathematical analysis of dynamics of cardiac memory and accommodation: theory and experiment

Watanabe

Koller²

2002

American Journal of Physiology-Heart and Circulatory Physiology

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Watanabe, Mari A., and Marcus L. Koller. Mathematical analysis of dynamics of cardiac memory and accommodation: theory and experiment. Am J Physiol Heart Circ Physiol 282: H1534-H1547, 2002. First published November 29, 2001 10.1152/ajpheart.00351.2001.-Decreasing the slope of the dynamic, but not conventional, restitution curves is antifibrillatory. Cardiac memory/accommodation underlies the difference. We measured diastolic interval (DI) and action potential duration (APD) in epicardial, endocardial, and Purkinje tissue from eight dogs. Consecutive 100-stimulus trains were given to study transitions between basic cycle lengths (BCL) ranging from 400 to 1,300 ms. (DI,APD) pairs aligned immediately on the line DI ϩ APD ϭ BCL (64/67) or oscillated (3/67). The shifting effect of up to 10 extrastimuli on restitution curves was also measured. These curves were fit with the equation APD ϭ ␣ ϩ ␤ exp(ϪDI/), where ␣ is asymptote, ␤ is drop, and is time constant. Linear regression of the parameters against the number of extrastimuli showed that premature and postmature stimuli decreased and increased ␣ and ␤ and increased and decreased , respectively. Analysis of a mathematical model treating memory as an exponentially decreasing shift of restitution curves shows that oscillatory DI,APD is expected with large ⌬BCL, steep restitution slope, or increased cardiac accommodation. The model explains phase shifts and suggests a common mechanism for Purkinje and myocardial electrical alternans. arrhythmias; dynamic restitution; short-term memory; modeling SUDDEN CARDIAC DEATH claims over 300,000 lives in the United States each year (53) despite the invention of the implantable cardiac defibrillator and improvement in antiarrhythmic drugs. A better understanding of the mechanisms of ventricular tachyarrhythmias is still needed for prediction and treatment of sudden cardiac death. Modeling studies predict that a steeply (Ͼ1) sloped action potential duration (APD) restitution curve should produce breakup of spiral waves into ventricular fibrillation, whereas a shallow slope should prevent ventricular fibrillation (23,36,37). Studies from patients with coronary artery disease (9, 52), and some animal studies (25,51) show that the maximum slope of the restitution curve can be much less than 1.If that were always true, ventricular fibrillation would never occur. A recent experiment designed to study this paradox demonstrated that the slope of the "dynamic" restitution curve, which is the relationship between APD and preceding diastolic interval (DI) measured during rapid pacing or during ventricular fibrillation, has a slope greater than that measured by the standard S1S2 protocol (25). The slope of the dynamic restitution curve has also been found to correlate with tachycardia stability. For example, verapamil, which was observed to convert ventricular fibrillation to ventricular tachycardia experimentally (49, 44), decreases the slope of the dynamic restitution curve, whereas procainamide, which decreases the slope of the standard ...

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“…During mechanical alternans, oscillations in contractile force are associated with oscillations in SR Ca 2ϩ release, and this alternans can be abolished by compounds such as caffeine (22) and ryanodine (15) that render the SR leaky to Ca 2ϩ . Ischemia and acidosis are known to facilitate the development of alternans (7,16) and to reduce the rate of SR Ca 2ϩ uptake (8), but 31 P NMR studies of failing SHHF and agematched WF rat hearts demonstrated no fall in intracellular pH with the induction of alternans (21). Moreover, as shown in a previous study, reducing the rate of SR Ca 2ϩ accumulation with thapsigargin does not decrease the threshold pacing frequency at which sustained mechanical alternans develops in healthy hearts (22).…”

Section: Discussionmentioning

confidence: 93%

Mechanical alternans and restitution in failing SHHF rat left ventricles

Dumitrescu

Narayan

Efimov

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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We examined mechanical alternans and electromechanical restitution in normal and failing rat hearts. Alternans occurred at 5 Hz in failing versus 9 Hz in control hearts and was reversed by 300 nM isoproterenol, 6 mM extracellular Ca2+, 300 nM −BAY K 8644, or 50 nM ryanodine. Restitution curves comprised phase I, which was completed before relaxation of the steady-state beat, and phase II, which occurred later. Phase I action potential area and developed pressure ratios were significantly reduced in the failing versus control hearts. Phase II was a monoexponential increase in relative developed pressure as the extrasystolic interval was increased. The plateau of phase II was significantly elevated in failing hearts. Thapsigargin (3 μM) plus ryanodine (200 nM) potentiated phase I to a significantly greater extent in control versus failing hearts and abolished phase II in both groups. The results suggest that both regulation of Ca2+ influx across the sarcolemma and Ca2+ release by the sarcoplasmic reticulum may contribute to altered excitation-contraction coupling in the failing spontaneously hypertensive heart failure prone rat heart.

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Electrical and mechanical alternans in canine myocardium in vivo. Dependence on intracellular calcium cycling.

Abstract: Activation time is one of the factors modifying electrical alternans. Delayed intracellular Ca2+ cycling plays a role in the concomitant occurrence of electrical and mechanical alternans.

Cited by 79 publications

References 29 publications

Mechanisms for Discordant Alternans

Mechanisms for Discordant Alternans

Mathematical analysis of dynamics of cardiac memory and accommodation: theory and experiment

Mechanical alternans and restitution in failing SHHF rat left ventricles

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