SPIRAL WAVE STABILITY IN PRESENCE OF CARDIAC MEMORY

存在心脏记忆的螺旋波稳定性

• 批准号: 6056152
• 负责人: Mari A. Watanabe
• 金额: $ 4.63万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-26 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6056152
• 关键词: action potentials; antiarrhythmic agent; biophysics; blood pressure; cardiovascular disorder prevention; computer simulation; electrophysiology; heart electrical activity; heart function; heart rate; implantable defibrillators; mathematical model; membrane channels; sudden cardiac death; tachycardia; ventricular fibrillation

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.

在美国，每年有30万人死于心源性猝死，三分之一接受抗心律失常药物和除颤器治疗的患者仍在5年内死亡。显然，需要更好的心源性猝死的预测和治疗方法。数学模型可以而且应该用来指导这种搜索。以前的数学模型的结果可以而且应该用来指导这个搜索。先前的数学模型结果表明，由于稳定的功能性再入（螺旋波），恢复函数的浅斜率会产生室性心动过速，而陡坡会使螺旋波不稳定并产生心室纤颤的情况很少见。最近的实验结果表明，与恢复曲线斜率相比，稳定动作电位持续曲线斜率与螺旋波破裂的关系更大，而稳定动作电位持续曲线的斜率依赖于心脏记忆。因此，记忆可以预期在螺旋波稳定性中发挥关键作用。心脏记忆从未在离子通道模型中被系统地研究过，本研究项目的广泛目标是通过构建一个包含心脏记忆的离子模型，并利用它来刺激心脏电反应性，在心脏的二维表示中，阐明心脏记忆在螺旋波诱导和稳定性中的作用。该模型的研究应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性。

项目成果

Mathematical analysis of dynamics of cardiac memory and accommodation: theory and experiment.

• DOI: 10.1152/ajpheart.00351.2001
• 发表时间: 2002-04
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: Mari A. Watanabe;M. Koller