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1 Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States
2 Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States; Center for Nonlinear and Complex Systems, Duke University, Durham, North Carolina, United States
3 Department of Pediatrics, Division of Pediatric Cardiology, Duke University Medical Center, Durham, North Carolina, United States; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States
* To whom correspondence should be addressed. E-mail: ann.pitruzzello{at}duke.edu.
Spatial heterogeneity of repolarization can provide a substrate for reentry to occur in myocardium. This heterogeneity may result from spatial differences in APD restitution. The restitution portrait (RP) measures many aspects of rate-dependent restitution: the dynamic restitution curve (RC), S1-S2 RC, and short-term memory response. We used the RP to characterize epicardial patterns of spatial heterogeneity of restitution that were repeatable across animals. NZW rabbit ventricles were paced from either the epicardial apex, mid-ventricle, or base, and optical action potentials were recorded from the same three regions. A perturbed downsweep pacing protocol was applied that measured the RP over a range of cycle lengths from 1000-140 ms. The time constant of short-term memory measured close to the stimulus was dependent on location. In the mid-ventricle the mean time constant was 19.1±1.1 sec, but it was 39% longer at the apex (p<0.01) and 23% longer at the base (p=0.03). The S1-S2 RC slope was dependent on pacing site (p=0.015), with steeper slope when pacing from the apex than from the base. There were no significant repeatable spatial patterns in steady-state APD at all cycle lengths or in dynamic RC slope. These results indicate that transient patterns of epicardial heterogeneity of APD may occur following a change in pacing rate. Thus, it may affect cardiac electrical stability at the onset of a tachycardia or during a series of ectopic beats. Differences in restitution with respect to pacing site suggest that vulnerability may be affected by the location of reentry or ectopic foci.
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