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.
| Watanabe, Mari A; Koller, Marcus L (2002) Mathematical analysis of dynamics of cardiac memory and accommodation: theory and experiment. Am J Physiol Heart Circ Physiol 282:H1534-47 |
| Watanabe, M A; Fenton, F H; Evans, S J et al. (2001) Mechanisms for discordant alternans. J Cardiovasc Electrophysiol 12:196-206 |
