Cellular mechanisms of differential action potential duration restitution in canine ventricular muscle cells during single versus double premature stimuli.

Kobayashi, Yoshinori; Peters, Werner; Khan, Steven S.; Mandel, William J.; Karagueuzian, Hrayr S.

doi:10.1161/01.cir.86.3.955

Cited by 41 publications

(30 citation statements)

References 47 publications

(15 reference statements)

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“…We never saw biphasic APD restitution curves (11,21,24,50) in which the ventricular myocardial restitution curve has a local maximum at short DI. The action potentials at this peak have been referred to as supernormal premature action potentials (3) and are believed to reflect potentiation of the calcium current.…”

Section: Resultsmentioning

confidence: 79%

“…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: 93%

“…Earlier studies studying the shift of restitution curves produced by multiple S2 using finer DI spacing showed that the slope of the early part (short DI) of the restitution curve was sharper for the second S2 (restitution curve after 1 premature stimulus) than for the first S2 (the standard restitution curve) (24,51). A reappraisal of the plots of the drop parameter against number of premature stimuli confirms the earlier re-sults in that the drop parameter is frequently larger for the second S2 in endocardium and Purkinje (not shown), usually in the transition from a large BCL to a BCL of 400 ms.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 79%

Section: Modeling Results and Implicationsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Many other protocols have been used: see for example 3 , Fenton et al 2002,Fox et al 2003d,Kobayashi et al 1992,Koller et al 1998.…”

Section: Preliminary Conceptsmentioning

confidence: 99%

An Ionically Based Mapping Model with Memory for Cardiac Restitution

et al. 2007

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Many features of the sequence of action potentials produced by repeated stimulation of a patch of cardiac muscle can be modeled by a 1D mapping, but not the full behavior included in the restitution portrait. Specifically, recent experiments have found that (i) the dynamic and S1-S2 restitution curves are different (rate dependence) and (ii) the approach to steady state, which requires many action potentials (accommodation), occurs along a curve distinct from either restitution curve. Neither behavior can be produced by a 1D mapping. To address these shortcomings, ad hoc 2D mappings, where the second variable is a "memory" variable, have been proposed; these models exhibit qualitative features of the relevant behavior, but a quantitative fit is not possible. In this paper we introduce a new 2D mapping and determine a set of parameters for it that gives a quantitatively accurate description of the full restitution portrait measured from a bullfrog ventricle. The mapping can be derived as an asymptotic limit of an idealized ionic model in which a generalized concentration acts as a memory variable. This ionic basis clarifies how the present model differs from previous models. The ionic basis also provides the foundation for more extensive cardiac modeling: e.g., constructing a PDE model that may be used to study the effect of memory on propagation. The fitting procedure for the mapping is straightforward and can easily be applied to obtain a mathematical model for data from other experiments, including experiments on different species.

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“…The RV was then paced with twice diastolic threshold current at 400-ms cycle length (CL) and the APD restitution curve constructed by the extrastimulus method 14,15 VF was then induced by rapid pacing, and the effects of PA were evaluated as in protocol 1.…”

Section: Protocolmentioning

confidence: 99%

Mechanism of Procainamide-Induced Prevention of Spontaneous Wave Break During Ventricular Fibrillation

Kim

Yashima

et al. 1999

Circulation

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Background-Ventricular fibrillation (VF) is maintained by 2 mechanisms: first by reentry formation and second by spontaneous wave break or wave splitting. We hypothesized that spontaneous wave break results from a critical shortening of the action potential duration (APD) during VF and that its prevention by procainamide eliminates spontaneous wave break. Methods and Results-The endocardial surfaces of 7 isolated, perfused swine right ventricles were mapped with a 3.2ϫ3.8 cm plaque with 477 bipolar electrodes. Activation pattern during VF was visualized dynamically while simultaneously recording epicardial action potentials with a glass microelectrode. APD restitution curves were constructed during VF (dynamic) and during S 1 S 2 protocols. At baseline, VF was maintained by 5.3Ϯ1 wavelets. Procainamide (PA) at 10 g/mL decreased the number of wavelets to 3.5Ϯ1 (PϽ0.05). At baseline VF was maintained by spontaneous wave break and by new reentrant wave front formation. PA eliminated spontaneous wave break during VF while having no effect on reentry formation. PA increased the cycle length of the VF (148.5Ϯ41.2 ms vs 81Ϯ10 ms, PϽ0.01) and the core area of the reentry from 5.8 to 14.5 mm 2 (PϽ0.05). Dynamic APD restitution curve during VF showed that PA eliminated the initiation of activation with APDs shorter than 30 ms. The effects of PA on cellular properties and wave front dynamics were reversed during 60 minutes of drug-free perfusion. Conclusions-Critically

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Cellular mechanisms of differential action potential duration restitution in canine ventricular muscle cells during single versus double premature stimuli.

Abstract: Greater variations of APD occur during the restitution of S3 than during S2 at short DIs. These differences appear to be caused by cyclic variations in tension and thus in [Ca2+]i. Calcium-sensitive outward currents could explain these differences in APD restitution.

Cited by 41 publications

References 47 publications

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

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

An Ionically Based Mapping Model with Memory for Cardiac Restitution

Mechanism of Procainamide-Induced Prevention of Spontaneous Wave Break During Ventricular Fibrillation

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