Copyright © 1993 by the European Society of Cardiology.
© 1993 The Europen Society of Cardiology
Ischaemia induced alternans of action potential duration in the intact-heart: dependence on coronary flow, preload and cycle length
First Medical Department Donauspital, Vienna, Austria
*Cardiovascular Medicine Division, Falk Cardiovascular Research Center, Stanford University School of Medicine Stanford, CA, U.S.A.
Pharmacology Department, School of Medicine, Georgetown University Washington, DC, U.S.A.
accepted 18 May 1993.
Correspondence: Robert W Kurz MD First Medical Department Donauspital, Langobardenstr 122, A-1220, Vienna, Austria.
Abstract
Clinical and experimental evidence relate action potential duration (APD) alternans to ischaemic heart disease and ventricular arrhythmias. The present investigation was performed to study the quantitative relationship between APD alternans and the degree ofischaemia, loading conditions and cycle length (CL) in an intact heart.
Monophasic action potentials (MAP) were simultaneously recorded by contact electrodes from two left (LV) undone right ventricular (RV) sites in 20 Langendorff-perfused rabbit hearts. The preparations were subjected to global ischaemia at flow rates ranging from 40% of normal flow to complete cessation of flow. Pacing was performed at either constant or regularly changing CL. The magnitude of APD alternans was expressed as beat-to-beat differences in action potential duration of two consecutive MAPs. During normal per fusion, neither very fast pacing at a CL of 200 ms nor periodical rate switches resulted in persistent APD alternans. Pacing at a constant CL of 800 ms did not induce A PD alternans at complete cessation of flow for 6 min. However, alternans developed progressively at a constant CL of 400 ms after 2.8±0.3 min of complete ischaemia at the pre-loaded LV, andafter 4.6±0.4 min at the unloaded RV (P<0.01). The reduction of preload at the LV from 15 to 5 mmftg end-diastolic pressure delayed development of APD alternans from 2.8±0.3 min to 4.3±0.4 min (P < 0.05) at 400 ms CL. Following graded under per fusion of 40%, 20% and 10% of initial flow, persistent APD alternans developed in relation to the degree of flow reduction and increased progressively with duration ofischaemia. APD alternans at the LV always preceded the onset of APD alternans at the RV. In experiments with identical flow rates the shortest CL of 200 ms resulted in the greatest and earliest initiation of APD alternans compared to the longer CL (P<0.01, P<0.001). An increase in CL from 400 to 800 ms immediately abolished APD alternans, generated by the shorter CL, at any time during the 6 min period of complete ischaemia. Similarly, increasing the cycle length from 200 or 400 to 600 ms eliminated APD alternans up to 6 min of ischaemia and significantly reduced its magnitude between 7 and 10 min within a few beats.
We conclude that persistent APD alternans is a characteristic finding in the rabbit heart during global ischaemia. It is a sensitive parameter of the severity of ischaemia and depends on the degree and duration of ischaemia as well as on the preload. The CL appears to have an independent effect on the generation of APD alternans, which is functionally separate from the effect of CL on the ischaemic burden. An eventual impact of these observations could be the application of APD alternans as a diagnostic tool in electrophysiological examinations of myocardial ischaemia in experimental and clinical settings.
Key Words: Alternans • action potential duration • ischaemia • monophasic action potentials • contact electrodes • Langendorff preparation
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