Action potential duration restitution and ventricular  fibrillation due to rapid focal excitation

Swissa, Moshe; Qu, Zhilin; Ohara, Toshihiko; Lee, Moon Hyoung; Lin, Shien‐Fong; Garfinkel, Alan; Karagueuzian, Hrayr S.; Weiss, James N.; Chen, Peng Sheng

doi:10.1152/ajpheart.00867.2001

Cited by 27 publications

(33 citation statements)

References 23 publications

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“…Yet, in principle, K ϩ current inhibition can also result in formation of additional spiral waves, especially in ventricular tissue. In situations with sufficient excitable tissue, this could lead to fibrillatory activity (134,362,412).…”

Section: Implications For Modes Of Drug Actionmentioning

confidence: 99%

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Schmitt

Grunnet

Olesen

2014

Physiological Reviews

202

197

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About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K+ channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K+ channels drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K+ channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure. The underlying posttranscriptional and posttranslational remodeling of the individual K+ channels changes their activity and significance relative to each other, and they must be viewed together to understand their role in keeping a stable heart rhythm, also under menacing conditions like attacks of reentry arrhythmia.

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Section: Implications For Modes Of Drug Actionmentioning

confidence: 99%

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Schmitt

Grunnet

Olesen

2014

Physiological Reviews

202

197

View full text Add to dashboard Cite

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“…1 Specifically, it is hypothesized that the slope of action potential duration (APD) restitution function, which relates diastolic interval (DI) and following APD, can predict stability of electrical activation. [2][3][4][5][6][7][8][9] The hypothesized mechanism is that a slope equal to or greater than 1 can lead to alternans of APD and block propagation. Activation block, in turn, facilitates reentry, leading to arrhythmia.…”

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confidence: 99%

Restitution of Action Potential Duration During Sequential Changes in Diastolic Intervals Shows Multimodal Behavior

Patwardhan

2004

Circulation Research

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Abstract-Restitution of action potential duration (APD) is thought to be critical in activation instability. Although restitution is used to predict APD during sequential changes in diastolic interval (DI), currently used protocols to determine restitution do not use sequential changes in DI. We explored restitution using a new pacing protocol to change DI sequentially and independently of APD. Transmembrane potentials were recorded from right ventricular endocardial tissue isolated from six dogs. We used three patterns of DIs: oscillatory, to demonstrate differences in APDs depending on previous activation history; random, to minimize effects of previous activation history, each DI preceding an APD had an equal probability of being short or long; and linear, to compare restitution relationship obtained during sequential changes in DI with those obtained using currently used protocols; DIs mimicked those that resulted using currently used protocols, except that they changed in sequence. During oscillatory DIs, restitution showed bimodal trajectory similar to hysteresis. Decrease in APD during decreasing DIs was faster than increase in APD during increasing DIs. When effects of previous activation history were minimized, we observed that for a given DI there were multiple values of APD. Restitution relationship obtained during sequential changes in DI was shallower than those obtained using currently used protocols. Our results show that the new pacing protocol may permit direct evaluation of effects of memory on APD. Sequential and explicit control of DI suggests that use of a unimodal relationship to predict APD when DIs change in sequence may not be appropriate. Key Words: action potential duration Ⅲ electrical restitution Ⅲ arrhythmia Ⅲ fibrillation C ardiac electrical restitution is considered to importantly influence whether an electrical disturbance degenerates into a reentrant activation. 1 Specifically, it is hypothesized that the slope of action potential duration (APD) restitution function, which relates diastolic interval (DI) and following APD, can predict stability of electrical activation. 2-9 The hypothesized mechanism is that a slope equal to or greater than 1 can lead to alternans of APD and block propagation. Activation block, in turn, facilitates reentry, leading to arrhythmia. Conversely, for slopes less than 1, disturbances in APD get smaller, returning to a stable activation. Consistent with this view, in a few animal studies, drugs that decrease the slope of restitution have been shown to have antiarrhythmic properties. 10,11 Therefore, it has been suggested that investigation of restitution relationship may prove helpful during development of treatments for arrhythmia or in evaluation of efficacy of antiarrhythmia drugs. 2 The APD restitution function is widely quantified using one of two pacing schemes. In one scheme, tissue is paced for several tens of beats at constant cycle length (S1) followed by a stimulus (S2) delivered at progressively shorter or longer intervals. The APD resultin...

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“…Third, the APD restitution curve determines the dynamical behaviour of tissue, and a sequence of closely coupled extrasystoles could produce re-entry through instability resulting from steepness of the APD restitution curve [23]. Again we did not address this question explicitly in the present study, but evidence from computational and experimental studies shows that re-entry may be produced in this way [24].…”

Section: Eads As a Trigger For Arrhythmiasmentioning

confidence: 87%