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Electrical and mechanical abnormalities play an important role in symptomatic individuals with LQTS or LQT subjects under the condition of low-dose isoproterenol, despite the paradoxic increase in the uncorrected QT interval. Profound electromechanical window(EMW) negativity correlates significantly with major arrhythmic events. However, how the relationship of electrical and mechanical is regulated in LQTS induced by cell surface ion channel expression levels degradation in hypokalemia is uncertain. This study is to determine the Electro-mechanical window(EMW; duration of LV-mechanical systole minus QT interval) in addition of isoproterenol infusion mimicking sympathetic stimuli, to find out whether it is responsible for the development of life-threatening arrhythmias either in vivo or in vitro under in hypokalemia or low K+ conditions. Moreover, it helps to provide further evidence to prove that EMW is superior in detecting arrhythmias than QT interval alone.
We used hypokalemia rabbit model induced by low potassium diet and performed electrocardiogram in in vivo. We also maked wedge of rabbit left ventricle and perfused with low K+ Tyrode's solution, contraction and a transmural electrocardiogram were simultaneously recorded in vitro. QT interval was subtracted from the duration of Q-onset to aortic-valve closure (QAoC) midline assessed non-invasively by continuous-wave echocardiography, measured in the same beat in hypokalemia rabbits. The effect of beta-adrenergic agonists isoproterenol on corrected QT interval(QTc) and Electro-mechanical window(EMW) were examined in vivo and in vitro. Western blot was carried out to observe the IKr protein and explore the molecular basis underlying the mechanism of isoproterenol in the process.
Hypokalemia prolonged corrected QT interval (0.32 ± 0.01 sec, versus 0.26 ± 0.03 sec before feeding; n = 3; P < 0.05) in rabbits. Low [K+]o (2 mmol/L) Tyrode's solution perfusion significantly prolonged QT interval in rabbit left ventricular arterially perfused wedges(370.33 ± 20.14ms, versus 347.33 ± 14.87ms before low K+ perfusion; n = 6; P < 0.05). Addition of isoproterenol(0.03ug/kg) decreased the QTc interval (0.24 ± 0.02 sec, versus 0.31 ± 0.00 sec before injection; n = 3; P < 0.05)in hypokalemia rabbits. However, in vitro ISO(100nM/L) decreased the negativity of EMW(154.67 ± 19.64ms, versus 170.00 ± 27.06ms before ISO perfusion; n = 3; P=0.437). The expression level of the IKr protein (110-kDa band) in rabbits on the low-K+ diet was much lower than that in control rabbits.
Beta-adrenergic stimulation decrease the negativity of EMW in low K+ solution induced LQT2 in vitro, probably because of potassium fluctuation during ISO infusion in wedges, in contrast with hypokalemia rabbits in vivo which IKrprotein expression levels was degraded, presented as permanently IKr blockage.