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Updated: May 11, 2026

Murine Isolated Heart Model of Myocardial Stunning Associated with Cardioplegic Arrest
Published on: August 6, 2015
Dispersion and delay of electrical restitution in the globally ischaemic heart
1Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, CA 94305.
Insights
Myocardial ischaemia disrupts action potential duration restitution, leading to delayed and non-uniform electrical restitution. This altered restitution is crucial for understanding ventricular fibrillation during heart attacks.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
Background:
- Action potential duration (APD) alternans precede ventricular fibrillation in ischaemic myocardium.
- APD alternans magnitude is influenced by ischaemia severity and APD restitution dynamics.
Purpose of the Study:
- To investigate how ischaemia affects APD restitution.
- To determine if ischaemia-induced changes in APD restitution are uniform across ventricular regions.
Main Methods:
- Monophasic action potentials recorded from rabbit ventricular epicardium.
- Electrical restitution curves assessed by varying inter-beat intervals during normal flow and ischaemia.
- Simultaneous recordings from right and left ventricular sites.
Main Results:
- Normal hearts exhibited rapid APD restitution with high inter-site uniformity.
- Ischaemia significantly slowed APD restitution, plateauing at longer cycle lengths over time.
- Ischaemia induced marked inter-site variability in APD restitution between RV and LV.
Conclusions:
- Global ischaemia delays electrical restitution.
- Ischaemia causes non-uniform electrical restitution across the ventricle.
- APD restitution abnormalities are critical factors in ischaemia-induced cardiac arrhythmias.
Abstract:
Alternans of action potential duration (APD) has been shown to be a precursor of ventricular fibrillation in ischaemic myocardium. We postulated that magnitude of alternans of APD during ischaemia depends not only on the severity of ischaemia but also on disturbed beat-to-beat restitution of APD. Monophasic action potentials were recorded simultaneously from right (RV) and left ventricular (LV) epicardial sites of isolated rabbit hearts. The inter-beat time courses of APD recovery were determined both during normal flow and ischaemia by interposing single cycle length changes ranging from 200 to 800 ms (= electrical restitution) simultaneously at the three recording sites. During normal perfusion, electrical restitution curves showed a steep initial recovery of APD, attaining steady-state values at extrastimulus cycle lengths of only 298 +/- 12 ms, with a high degree of uniformity between the three recording sites (inter-site variability < 2%). Ischaemia produced a marked slowing of electrical restitution which, on average, reached a plateau at extrastimulus cycle lengths of 415 +/- 45 ms, 650 +/- 72 ms and > 800 ms at 2 min, 5 min and 9 min of ischaemia, respectively (each P < 0.001 vs control). In addition, ischaemia resulted in a large inter-site variability, with RV and LV restitution curves deviating from each other by as much as 28.5% (P < 0.0001 vs baseline). We conclude that global ischaemia not only leads to a delayed but also non-uniform electrical restitution.(ABSTRACT TRUNCATED AT 250 WORDS)
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