COMPUTER MODELLING OF PROPAGATION IN THE HEART

该提案要求支持购买设备（一个中央计算单元），用于满足纽约州锡拉丘兹纽约州立大学健康科学中心药理学、微生物学和医学系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。该计划代表了一个多学科的方法，其总体目标是实现正常和异常的心肌电波传播的理解。我们的努力是为了阐明波在心脏中传播的潜在二维和三维动力学，再入性室性心动过速的机制，以及决定主要心脏间隙连接（Cx43）蛋白和延迟整流钾通道（HERG）的门控行为的结构-功能关系，这是从人体组织中克隆出来的。会议的中心主题是“细胞间通信和脉冲传播”，这是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，将一组研究人员、各个相关领域的专家聚集在一起，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，参与一个富有成效的合作研究计划。本项目的主要支持来自国家心肺血液研究所的计划项目资助（PO1 HL39707）。美国心脏协会和北美起搏和电生理学会也提供支持。此外，惠特克基金会（Whitaker Foundation）以及美国国立卫生研究院（NIH）正在以RO1的形式向我们的两名研究人员提供资金。自1982年以来，我们研究小组的不断发现取得了丰硕的成果。例如，在过去的5年里，我们发表了85篇同行评议论文，对理解细胞间通讯和脉冲传播的基本机制做出了重大贡献。我们小组的一个主要优势是能够成功地将正常和异常条件下电脉冲传播细胞机制的实验研究与旨在预测心脏组织行为的计算机建模研究相结合。计算机模型是一个重要的工具，以制定假设关于离子机制，和传播动力学的心律失常的起源。我们的目标是在未来的研究中继续使用这种结合实验和计算机建模的方法。

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.