Integrative computational and experimental study of arrhythmogenesis and defibrillation in acute myocardial ischaemia

急性心肌缺血心律失常发生和除颤的综合计算和实验研究

• 批准号: G0700278/1
• 负责人: Blanca Rodriguez
• 金额: $ 113.33万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0700278%2F1
• 关键词: Integrative; computational; experimental; study; arrhythmogenesis

We aim at finding the mechanisms by which myocardial ischaemia results in lethal ventricular arrhythmias and changes in defibrillation efficacy. We expect this new insight will help in optimizing defibrillation therapy in patients suffering from coronary heart disease. Sudden cardiac death subsequent to ventricular fibrillation is the leading cause of mortality in the UK. In 80% of the victims, the arrhythmia arises in consequence of mismatch between cardiac oxygen supply and demand (myocardial ischaemia), caused by coronary heart disease. The only effective therapy to avert sudden cardiac death is electrical defibrillation: timely application of an electric shock to the myocardium. However, although the majority of patients undergoing defibrillation suffer from ischaemia, research has mostly focused on uncovering the mechanisms of defibrillation in the normal myocardium. This is in part due to the complexity and the rapidity of ischaemia-induced alterations in myocardial electrophysiological properties, which render experimental evaluation of the underlying mechanisms very difficult. We will develop a novel anatomically-based rabbit model of the regionally-ischaemic ventricles, validated using experimental data from the ionic to the whole organ level. We then will conduct a combination of computer simulations and experiments to investigate changes in arrhythmia and defibrillation mechanisms in acute myocardial ischaemia.

我们的目的是发现心肌缺血导致致死性室性心律失常和除颤效果变化的机制。我们希望这一新的见解将有助于优化冠心病患者的除颤治疗。在英国，室颤后的心源性猝死是死亡的主要原因。在80%的受害者中，心律失常是由于冠心病引起的心脏氧供应和需求之间的不匹配（心肌缺血）而引起的。避免心脏性猝死的唯一有效疗法是电除颤：及时对心肌进行电击。然而，尽管大多数接受除颤的患者患有缺血，但研究主要集中在揭示正常心肌中除颤的机制。这在一定程度上是由于缺血引起的心肌电生理特性改变的复杂性和快速性，这使得对潜在机制的实验评价非常困难。我们将开发一种新的基于解剖学的局部缺血心室兔模型，使用从离子到整个器官水平的实验数据进行验证。然后，我们将进行计算机模拟和实验相结合，以研究急性心肌缺血时心律失常和除颤机制的变化。