Effects of potassium channel openers in the isolated perfused hypokalaemic murine heart

AIM: We explored the anti-arrhythmic efficacy of K(+) channel activation in the hypokalaemic murine heart using NS1643 and nicorandil, compounds which augment I(Kr) and I(KATP) respectively. METHODS: Left ventricular epicardial and endocardial monophasic action potentials were compared in normokalaemic and hypokalaemic preparations in the absence and presence of NS1643 (30 μm) and nicorandil (20 μm). RESULTS: Spontaneously beating hypokalaemic hearts (3 mm K(+)) all elicited early afterdepolarizations (EADs) and episodes of ventricular tachycardia (VT). Perfusion with NS1643 and nicorandil suppressed EADs and VT in 7 of 13 and five of six hypokalaemic hearts. Provoked arrhythmia studies using programmed electrical stimulation induced VT in all hypokalaemic hearts, but failed to do so in 7 of 13 and five of six hearts perfused with NS1643 and nicorandil respectively. These anti-arrhythmic effects were accompanied by reductions in action potential duration at 90% repolarization (APD(90)) and changes in the transmural gradient of repolarization, reflected in ΔAPD(90). NS1643 and nicorandil reduced epicardial APD(90) from 68.3 ± 1.1 to 56.5 ± 4.1 and 51.5 ± 1.5 ms, respectively, but preserved endocardial APD(90) in hypokalaemic hearts. NS1643 and nicorandil thus restored ΔAPD(90) from −9.6 ± 4.3 ms under baseline hypokalaemic conditions to 3.9 ± 4.1 and 9.9 ± 2.1 ms, respectively, close to normokalaemic values. CONCLUSION: These findings demonstrate, for the first time, the anti-arrhythmic efficacy of K(+) channel activation in the setting of hypokalaemia. NS1643 and nicorandil are anti-arrhythmic through the suppression of EADs, reductions in APD(90) and restorations of ΔAPD(90).