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Effects of potassium channel openers in the isolated perfused hypokalaemic murine heart
Author(s) -
Killeen M. J.,
Thomas G.,
Olesen S.P.,
Demnitz J.,
Stokoe K. S.,
Grace A. A.,
Huang C. L.H.
Publication year - 2008
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2007.01773.x
Subject(s) - potassium channel , potassium , hypokalemia , cardiology , medicine , chemistry , organic chemistry
Abstract 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 μ m ) and nicorandil (20 μ m ). Results: Spontaneously beating hypokalaemic hearts (3 m m 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 .