EFFECTS OF PREMATURE BEATS ON REPOLARIZATION OF POSTEXTRASYSTOLIC BEATS

Background A short-long-short sequence of cycle lengths predisposes to reentrant tachyarrhythmias. There is limited information about the ef fects of premature ventricular contractions (PVCs) on repolarization o f postextrasystolic depolarizations (PEDs). Such information would con tribute to understanding the mechanism for facilitating reentry with s hort-long-short cycle lengths. Methods and Results We introduced PVCs, over a range of coupling intervals and during a range of basic drive cycle lengths (BCLs), and determined PED repolarization. Our results f rom whole-animal experiments, isolated cell studies, and computer simu lations are reported. In the whole-animal experiments, PED refractory periods (RPs) were longer than RP(BCL). The greatest difference betwee n RP(PED) and RP(BCL) (Delta RP(max)) occurred after short coupling in terval PVCs and was 4.3+/-0.8, 4.2+/-0.8, and 2.1+/-0.5 ms (mean+/-SEM ) during drives with short, intermediate, and long BCLs, respectively. The diastolic interval preceding the PED (DIPED) was inversely relate d to the coupling interval between the basic drive beat and the PVC an d directly related to RP(PED). FED action potential durations (APDs) o f isolated canine myocytes were 9.8+/-4.9 ms (mean+/-SEM) longer than APD BCL (n=19). The DiFrancesco-Noble membrane equations were used in simulations of action potential propagation in a one-dimensional cable , with stimulation protocols duplicating those in the animal experimen ts. PVCs prolonged APD(PED), and APD(PED) was prolonged more during sh ort than during long BCL drives. There was a direct relation between D IPED and APD(PED). Analysis of the membrane currents over the time cou rse of the PVCs and PEDs suggested that the ionic basis for PED repola rization prolongation was the interaction of I-to and I-K. Hyperpolari zing constant-current injections introduced immediately after the spik e of isolated myocyte action potentials caused APD prolongation. This observation is consistent with the I-to and I-K interaction causing PE D repolarization prolongation. Conclusions PED repolarization prolonga tion could provide sites for unidirectional block to propagation of PV Cs after PEDs and could facilitate initiation of reentrant tachyarrhyt hmias after short-long-short sequences of cycle lengths.