SPIRAL WAVE STABILITY IN PRESENCE OF CARDIAC MEMORY

在美国，每年有30万人死于心脏性猝死，而接受抗心律失常药物和除颤器治疗的患者中，仍有三分之一在5年内死亡。显然，需要更好的心脏性猝死的预测指标和治疗方法。数学模型可以而且应该被用来指导这种搜索。以前的数学模型的结果可以而且应该用来指导这次搜索。以往数学模型的结果表明，由于稳定的功能折返(螺旋波)，重建函数的浅斜率会产生室性心动过速，而陡峭的斜率会破坏螺旋波的稳定，并产生室颤，这种情况很少见。最近的实验结果表明，与恢复曲线的斜率相比，稳态动作电位时程曲线的斜率与螺旋波破裂更相关，而稳定动作电位持续曲线的斜率取决于心脏记忆。因此，可以预期，记忆将在螺旋波的稳定性中发挥关键作用。在离子通道模型中，心脏记忆从未被系统地研究过，本研究项目的广泛目标是通过构建一个结合了心脏记忆的离子模型，并用它来刺激心脏的二维表示，来阐明心脏记忆在螺旋波诱导和稳定性中的作用。对这一模型的研究应该确定抗心动过速和抗纤颤药物在恢复和心脏记忆方面所具有的理想特征。

Broad, long term objectives 300,000 people in the USA each year from sudden cardiac death and a third of patients treated with anti-arrhythmic drugs and defibrillators still die within 5 years. Clearly, better predictors and treatment methods of sudden cardiac death are needed. Mathematical models can and should be used to guide this search. Results from previous mathematical models can and should be used to guide this search. Results from previous mathematical models indicate that a shallow slope of the restitution function should produce ventricular tachycardia due to stable functional reentry (spiral waves) and a steep slope should destabilize spiral waves and produce ventricular fibrillation are rarely seen. Recent experimental results indicate that the slope of the steady action potential duration curve, which is known to depend on cardiac memory, is more relevant to spiral wave breakup than restitution curve slope is. Therefore, memory can be expected to play a key role in spiral wave stability. Cardiac memory has never been systematically investigated in ionic channel models, and the broad objective of this research project is to clarify the role of cardiac memory in spiral wave induction and stability, by constructing an ionic model that incorporates cardiac memory and using it to stimulate cardiac electrical reactivity, in a two dimensional representation of the heart. Study of this model should identify desirable characteristics for anti-tachycardiac and anti-fibrillatory drugs to possess with respect to their effects on restitution and cardiac memory.