COMPUTER MODELLING OF PROPAGATION IN THE HEART

这项提案请求支持购买设备(中央计算单元)，用于满足7名独立调查人员的计算机建模、数据处理和数据分析需求，这些独立调查人员在纽约锡拉丘兹的纽约州立大学健康科学中心的药理学、微生物学和医学系工作。该计划代表了一种多学科的方法，其总体目标是实现对心肌中正常和异常电波传播的了解。我们致力于阐明波在心脏中传播的二维和三维动力学，折返性室性心律失常的机制，以及决定主要心脏缝隙连接(Cx43)蛋白和从人体组织克隆的延迟整流钾通道(HERG)门控行为的结构-功能关系。中心主题是“细胞间通讯和脉冲传播”，讨论了一个与临床相关的重要科学主题，并提供了一个独特的机会，让一群研究人员和相关领域的专家，包括细胞电生理学、生物物理学、生物医学工程、数学、计算机科学和分子生物学，在一个富有成效的合作研究计划中汇聚一堂。该项目的主要支持来自国家心肺血液研究所的项目资助(PO1 HL39707)。美国心脏协会和北美起搏和电生理学学会也提供了支持。此外，惠特克基金会以及美国国立卫生研究院以我们两名研究人员的RO1赠款的形式提供的资金正在等待中。自1982年以来，我们的研究小组不断地取得了丰硕的成果。例如，在过去的5年里，我们发表了85篇同行评议论文，对理解细胞间通信和脉冲传播的基本机制做出了重大贡献。我们团队的一个主要优势是能够成功地将关于正常和异常条件下电脉冲传播的细胞机制的实验研究与旨在预测心脏组织行为的计算机模拟研究相辅相成。计算机模型是阐明有关心律失常发生的离子机制和传播动力学假说的重要工具。我们的目标是在未来的研究中继续使用这种实验和计算机建模相结合的方法。

This proposal requests support to purchase equipment (a central computational unit) that will be used to fulfill the computer modeling, data processing and data analysis needs of 7 independent investigators working the Departments of Pharmacology, Microbiology and Medicine at the SUNY Health Science Center in Syracuse, NY. The program represents a multidisciplinary approach whose overall objective is to achieve an understanding of normal and abnormal electrical wave propagation in cardiac muscle. Our efforts are directed toward elucidating the underlying two- and three-dimensional dynamics of wave propagation in the heart and the mechanisms of reentrant ventricular tachyarrhythmias, as well as the structure-function relations that determine gating behavior of the major cardiac gap junction (Cx43) protein and of a delayed rectifier potassium channel (HERG) which as been cloned from human tissue. The central theme, "Intercellular Communication and Impulse Propagation", addresses an important scientific topic of clinical relevance, and allows the unique opportunity of bringing together a group of investigators, experts in various relevant fields, including cellular electrophysiology, biophysics, biomedical engineering, mathematics, computer science and molecular biology, in a productive cooperative research program. Major support of this program comes from a Program Project Grant (PO1 HL39707) from the National Heart Lung and Blood Institute. Support is provided also by the American Heart Association and the North American Society of Pacing and Electrophysiology. In addition, funding is pending from the Whitaker Foundation, as well as from NIH in the form of RO1 grant of two of our investigators. Continuous finding of our research group since 1982 has been exceedingly fruitful. For example, over the last 5 years we have published 85 peer-review papers and have contributed significantly to the understanding of fundamental mechanisms of intercellular communication and impulse propagation. A major strength of our group is its ability to successfully complement experimental studies on the cellular mechanisms of propagation of electrical impulses under normal and abnormal conditions with computer modeling studies aimed at predicting heart tissue behaviors. Computer models are an essential tool to formulate hypotheses regarding ionic mechanisms, and propagation dynamics of the genesis of cardiac arrhythmias. It is our goal to continue using such a combined experimental-computer modeling approach in our future studies.