Systematic analysis of crosstalk between arrhythmic triggers using functional and mathematical approaches.

为了解长QT间期所致心律失常易感性性别差异的潜在机制，分析了诱发心律失常的三种全身因素（性激素、交感神经系统刺激和药物）。然后我们发现性激素的非基因组作用参与了性别差异，一氧化氮调节K+通道的新机制，以及雌激素对QT延长药物敏感性的影响。将这些数据引入心脏动作电位的计算机仿真模型。该模型可用于评价延长QT间期药物诱发心律失常的性别差异。

To understand the underlying mechanisms of sex-difference in susceptibility ofarrhythmias induced by long QT intervals, there systemic factors for triggers ofarrhythmias (sex hormones, sympathetic nervous system stimulation, and drugs) wereanalyzed. We then found an involvement of non-genomic action of sex-hormones in the sexdifference, a novel mechanism for regulation of a K+ channel by nitric oxide, and effectsof estrogen on sensitivity of QT-prolonging drugs. These data were introduced into acomputer simulation model of cardiac action potentials. The model could assess the sexdifference of susceptibility of arrhythmias induced by QT-prolonging drugs.