Abstract
This study investigates the development of the spatiotemporal pattern of action potential alternans during acute regional ischemia. Experiments were carried out in isolated Langendorff-perfused rabbit heart using a combination of optical mapping and microelectrode recordings. The alternans pattern significantly changed over time and had a biphasic character reaching maximum at 6–9 min after occlusion. Phase I (3–11 minutes of ischemia) is characterized by rapid increase in the alternans magnitude and expansion of the alternans territory. Phase I is followed by gradual decline of alternans (Phase II) in both magnitude and territory. During both phases we observed significant beat-to-beat variations of the optical action potential amplitude (OAPA) alternans. Simultaneous microelectrode recordings from subepicardial and subendocardial layers showed that OAPA alternans coincided with intramural 2 : 1 conduction blocks. Our findings are consistent with the modeling studies predicting that during acute regional ischemia alternans can be driven by 2 : 1 conduction blocks in the ischemic region.
Highlights
Beat-to-beat alternation of the action potential at increased heart rates is extensively used as an empirical midterm and long-term ECG-predictor of ventricular arrhythmias and sudden cardiac death [1,2,3]
We investigated the evolution of the spatial pattern of the action potential alternans during early stages (
In control experiments without inducing no-flow ischemia, we did not see any changes in action potential duration, propagation velocity, or alternans for at least 30 minutes, which significantly exceeds the duration of our acute ischemia experiments
Summary
Beat-to-beat alternation of the action potential at increased heart rates is extensively used as an empirical midterm and long-term ECG-predictor of ventricular arrhythmias and sudden cardiac death [1,2,3]. Multiple clinical studies have demonstrated upsurge in T-wave alternans and repolarization heterogeneity precede spontaneous initiation of ventricular tachyarrhythmias in humans [6, 7]. In this context, acute regional ischemia, which is known to cause rapid development of conduction abnormalities and arrhythmias, is a useful model for investigating the link between these abnormalities and alternans at short time scales. The goal of our study is to overcome these limitations by utilizing optical mapping, the technology, which enables detailed spatiotemporal characterization of action potential alternans and which has been proved to be valuable for the analysis of the alternans’ mechanisms [10,11,12,13]
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