K-ATP channels and 'border zone' arrhythmias: role of the repolarization dispersion between normal and ischaemic ventricular regions

1 In order to investigate the role of K-ATP channel activation and repolari zation dispersion on the 'border zone' arrhythmias induced by ischaemia-rep erfusion, the effects of glibenclamide and bimakalim, agents modifying acti on potential (AP) duration, were studied in an in vitro model of myocardial 'border zone'. 2 The electrophysiological effects of 10 mu M glibenclamide and 1 mu M bima kalim (n=8 each), respectively K-ATP channel blocker and activator, were in vestigated on guinea-pig ventricular strips submitted partly to normal cond itions (normal zone, NZ) and partly to simulated ischaemic then reperfused conditions (altered zone, AZ). 3 By preventing the ischaemia-induced AP shortening (P<0.0001), glibenclami de reduced the dispersion of AP duration 90% (APD(90)) between NZ and AZ (P <0.0001), and concomitantly inhibited the 'border zone' arrhythmias induced by an extrastimulus (ES), their absence being significantly related to the lessened APD(90) dispersion (chi(2) = 8.28, P<0.01). 4 Bimakalim, which also reduced the APD(90) dispersion (P<0.005) due to dif ferential AP shortening in normal and ischaemic tissues, decreased the inci dence of myocardial conduction blocks (25% of preparations versus 83% in co ntrol, n=12, P<0.05) and favoured 'border zone' spontaneous arrhythmias (75 % of preparations versus 25% in control, P<0.05). 5 During reperfusion, unlike bimakalim, glibenclamide inhibited the ES-indu ced arrhythmias and reduced the incidence of the spontaneous ones (12% of p reparations versus 92% in control, P<0.05), this latter effect being signif icantly related (chi(2) = 6.13, P<0.02) to the lessened ischaemia-induced A P shortening in the presence of glibenclamide (P<0.0001). 6 These results suggest that K-ATP blockade may protect the ischaemic-reper fused myocardium from 'border zone' arrhythmias concomitantly with a reduct ion of APD(90) dispersion between normal and ischaemic regions. Conversely, K-ATP channel activation may modify the incidence of conduction blocks and exacerbate the ischaemia-induced 'border zone' arrhythmias.