S. Picard et al., K-ATP channels and 'border zone' arrhythmias: role of the repolarization dispersion between normal and ischaemic ventricular regions, BR J PHARM, 127(7), 1999, pp. 1687-1695
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.