Dispersion and delay of electrical restitution in the globally ischaemic heart

Altemans of action potential duration (APD) has been shown tobe a precursor of ventricular fibrillation in ischaemic myocardium.We postulated that magnitude of alternans of APD during ischaemiadepends not only on the severity of ischaemia but also on disturbedbeat-to-beat restitution of APD. Monophasic action potentials were recorded simultaneously fromright (RV) and left ventricular (LV) epicardial sites of isolatedrabbit hearts. The inter-beat time courses of APD recovery weredetermined both during normal flow and ischaemia by interposingsingle cycle length changes ranging from 200 to 800 ms (=electricalrestitution) simultaneously at the three recording sites. During normal perfusion, electrical restitution curves showeda steep initial recovery of APD, attaining steady-state valuesat extrastimulus cycle lengths of only 298±12 ms, witha high degree of uniformity between the three recording sites(inter-site variability <2%). Ischaemia produced a markedslowing of electrical restitution which, on average, reacheda plateau at extrastimulus cycle lengths of 415±45 ms,650 ± 72 ms and >800 ms at 2 min, 5 min and 9 minof 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 otherby as much as 28·5% (P<0·0001 vs baseline). We conclude that global ischaemia not only leads to a delayedbut also non-uniform electrical restitution. The delay in electricalrestitution may be causally related to the development of alternansof APD, whereas the dispersion of electrical restitution mayproduce electrical instability and set the stage for ischaemia-relatedventricular arrhythmias.