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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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Compared with a routine radiation dose FBP protocol, 50% reduced dose acquisition using IR preserves image quality and diagnostic accuracy at coronary CTA.

Our results indicate that mechanism of repolarization alternans has restitution-dependent and restitution-independent components. However, our results also provide direct evidence that shows that DI-dependent restitution of APD is not a necessary mechanism for the alternans to exist. Ability to pace with explicit control of DI provides a novel approach to dissect mechanisms of alternans into restitution-dependent and restitution-independent effects.