Copyright © 1994 by the European Society of Cardiology.
© 1994 The European Society of Cardiology
Dispersion and delay of electrical restitution in the globally ischaemic heart
From the Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine Stanford, CA 94305, U.S.A.
Received 25 August 1993; revised 1 December 1993; .
Correspondence: Michael R. Franz, MD, PhD, Pharmacology Department, Room NE 403, School of Medicine, Georgetown University, 3900 Reservoir Road, Washington, DC 20007, U.S.A.
Abstract
Altemans 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, iscliaemia 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. The delay in electrical restitution may be causally related to the development of alternans of APD, whereas the dispersion of electrical restitution may produce electrical instability and set the stage for ischaemia-related ventricular arrhythmias.
Key Words: Ischaemia • monophasic • action potentials • contact electrodes • Langendorff preparation • electrical restitution • dispersion • alternans • action potential duration
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