Effects of potassium channel openers in the isolated perfused hypokalaemic murine heart |
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Authors: | Killeen M J Thomas G Olesen S-P Demnitz J Stokoe K S Grace A A Huang C L-H |
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Institution: | Physiological Laboratory, University of Cambridge, Cambridge, UK. mjk42@cam.ac.uk |
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Abstract: | Aim: We explored the anti‐arrhythmic efficacy of K+ channel activation in the hypokalaemic murine heart using NS1643 and nicorandil, compounds which augment IKr and IKATP 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 (APD90) and changes in the transmural gradient of repolarization, reflected in ΔAPD90. NS1643 and nicorandil reduced epicardial APD90 from 68.3 ± 1.1 to 56.5 ± 4.1 and 51.5 ± 1.5 ms, respectively, but preserved endocardial APD90 in hypokalaemic hearts. NS1643 and nicorandil thus restored ΔAPD90 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 APD90 and restorations of ΔAPD90. |
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Keywords: | hypokalaemia mouse heart nicorandil NS1643 |
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