1 In order to investigate the role of K ATP channel activation and repolarization dispersion on thè border zone' arrhythmias induced by ischaemia-reperfusion, the e ects of glibenclamide and bimakalim, agents modifying action potential (AP) duration, were studied in an in vitro model of myocardial`border zone'. 2 The electrophysiological e ects of 10 mM glibenclamide and 1 mM bimakalim (n=8 each), respectively K ATP channel blocker and activator, were investigated on guinea-pig ventricular strips submitted partly to normal conditions (normal zone, NZ) and partly to simulated ischaemic then reperfused conditions (altered zone, AZ).3 By preventing the ischaemia-induced AP shortening (P50.0001), glibenclamide reduced the dispersion of AP duration 90% (APD 90 ) between NZ and AZ (P50.0001), and concomitantly inhibited the`border zone' arrhythmias induced by an extrastimulus (ES), their absence being signi®cantly related to the lessened APD 90 dispersion (w 2 =8.28, P50.01). 4 Bimakalim, which also reduced the APD 90 dispersion (P50.005) due to di erential AP shortening in normal and ischaemic tissues, decreased the incidence of myocardial conduction blocks (25% of preparations versus 83% in control, n=12, P50.05) and favoured`border zone' spontaneous arrhythmias (75% of preparations versus 25% in control, P50.05). 5 During reperfusion, unlike bimakalim, glibenclamide inhibited the ES-induced arrhythmias and reduced the incidence of the spontaneous ones (12% of preparations versus 92% in control, P50.05), this latter e ect being signi®cantly related (w 2 =6.13, P50.02) to the lessened ischaemiainduced AP shortening in the presence of glibenclamide (P50.0001). 6 These results suggest that K ATP blockade may protect the ischaemic-reperfused myocardium from border zone' arrhythmias concomitantly with a reduction 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.
Dofetilide 5 nmol/L decreased APD(90) dispersion between NZ and AZ and reduced the early ES-induced arrhythmias. However, dofetilide 50 nmol/L increased APD(90) dispersion, and at 10 and 50 nmol/L, it increased the late spontaneous arrhythmias.
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