Low flow reperfusion after acute myocardial ischemia: when too little is too much

急性心肌缺血后的低流量再灌注：太少就是太多

• 批准号: 8454499
• 负责人: Matthew W. Kay
• 金额: $ 31.67万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-19 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8454499
• 关键词: Acute; Address; Affect; Area; Arrhythmia; Biomedical Engineering; Breeding; Calcium; Cardiac; Computer software; Coronary; Coronary heart disease; Custom; Development; Disease; Electrocardiogram; Electrophysiology (science); Exposure to; Faculty; Fiber; Fluorescence; Goals; Heart; Heterogeneity; Image; Injury; Investments; Ischemia; Ischemic Preconditioning; Kinetics; Knowledge; Life; Lighting; Link; Measurement; Measures; Mechanics; Membrane Potentials; Metabolic; Metabolism; Methodology; Methods; Modification; Monitor; Morphologic artifacts; Motion; Myocardial Ischemia; Myocardial tissue; Myocardium; NADH; Organ; Pathologic; Perfusion; Photobleaching; Physiologic pulse; Physiological; Physiology; Positioning Attribute; Preparation; Preventive; Protocols documentation; Publishing; Reperfusion Therapy; Research; Resolution; Resources; Signal Transduction; System; Tachyarrhythmias; Techniques; Temperature; Testing; Therapeutic Intervention; Time; Tissues; Ultrasonography; Ultraviolet Rays; United States; Unstable angina; Ventricular; Work; base; charge coupled device camera; clinically relevant; computerized data processing; design; detector; experience; fluorescence imaging; heart electrical activity; heart metabolism; imaging modality; improved; insight; instrument; instrumentation; muscle metabolism; novel; preconditioning; prevent; public health relevance; research study; sudden cardiac death; synergism; tool

DESCRIPTION (provided by applicant): In United States almost 6.5 million people are living with coronary heart disease. During episodes of unstable angina, the affected myocardial tissue experiences transient episodes of acute ischemia followed by reperfusion, often at reduced flow rates. The overall goal of the work proposed in this application is to study mechanisms of ischemia and reperfusion arrhythmias from a new perspective: that of connecting local changes in tissue metabolism caused by perturbations in coronary flow to the resulting disturbances in electrical activity. Despite a clear causative link between cardiac muscle metabolism and its electrical activity, surprisingly few studies have attempted to study them together in working heart preparations using fluorescence imaging. The proposed studies aim to fill this gap. Specific Aim 1 is to increase the capabilities of our existing dual imaging system by incorporating 1) a high resolution camera for fast imaging of NADH fluorescence, 2) pulsed ultraviolet light illumination that is gated to the ECG, and 3) hardware and software for a third fluorescence imaging camera. Specific Aim 2 is to implement techniques that will allow arrhythmias resulting from metabolic disturbances to be studied at physiologic temperatures (37oC) using working heart preparations. Specific Aim 3 is to use multi-mode fluorescence imaging to study specific pathologic conditions in working heart preparations of acute ischemic injury and subsequent reperfusion. These conditions include: rapid pacing, fibrillation, low-flow reperfusion, and ischemic preconditioning. With these Aims, we will provide major advances in the methodology required to conduct studies at the intersection of the research fields of coronary flow, cardiac metabolism, and cardiac electrophysiology while also providing the potential to gain improved understanding of the physiology that causes lethal arrhythmias during unstable coronary flow. Ultimately, this will provide new insights into possible therapeutic interventions to prevent sudden cardiac death.

描述（由申请人提供）：在美国，近 650 万人患有冠心病。在不稳定心绞痛发作期间，受影响的心肌组织经历短暂的急性缺血发作，然后再灌注，通常流速降低。本申请提出的工作的总体目标是从新的角度研究缺血和再灌注心律失常的机制：将冠状动脉血流扰动引起的组织代谢的局部变化与由此产生的电活动干扰联系起来。尽管心肌代谢与其电活动之间存在明显的因果关系，但令人惊讶的是，很少有研究尝试使用荧光成像在工作心脏准备过程中将它们一起研究。拟议的研究旨在填补这一空白。具体目标 1 是通过整合 1）用于快速成像 NADH 荧光的高分辨率相机，2）门控至 ECG 的脉冲紫外光照明，以及 3）用于第三荧光成像相机。具体目标 2 是实施技术，使代谢紊乱引起的心律失常能够在生理温度 (37oC) 下使用工作心脏制剂进行研究。具体目标 3 是使用多模式荧光成像来研究急性缺血性损伤和随后再灌注的工作心脏准备中的特定病理条件。这些情况包括：快速起搏、颤动、低流量再灌注和缺血预处理。凭借这些目标，我们将在冠状动脉血流、心脏代谢和心脏电生理学研究领域的交叉领域进行研究所需的方法方面取得重大进展，同时也有可能更好地了解导致致命性心律失常的生理学。冠状动脉血流不稳定。最终，这将为预防心源性猝死的可能治疗干预措施提供新的见解。