Core B: Functional Assessment & Instrumentation

核心 B：功能评估

• 批准号: 10627576
• 负责人: JEFFREY L ARDELL
• 金额: $ 43.18万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10627576
• 关键词: Animals; Area; Biological Markers; Blood Vessels; Cardiac; Catecholamines; Characteristics; Chronic; Conscious; Coupled; Data; Dedications; Detection; Devices; Electrodes; Electrophysiology (science); Epicardium; FDA approved; Family suidae; Film; Goals; Heart; Heterogeneity; Human; Implant; In Vitro; Infarction; Maps; Measurement; Measures; Modeling; Monitor; Myocardial Infarction; Myocardial Ischemia; Myocardium; Nerve; Nervous System; Neuropeptides; Neurotransmitters; Operative Surgical Procedures; Optics; Pathology; Patients; Periodicity; Phase; Pre-Clinical Model; Preparation; Research; Resolution; Structure of stellate ganglion; Technology; Telemetry; Temperature; Therapeutic; Therapeutic Intervention; Thinness; Time; Titrations; bioelectronics; design; experience; heart rate monitor; high risk; instrumentation; neural; neurochemistry; neuroregulation; neurotransmitter release; porcine model; programs; sudden cardiac death; temporal measurement

ABSTRACT – Scientific Core - Function The primary goal of scientific Core B – “Functional Assessment and Instrumentation core” - is to optimize bioelectronic technologies for high-resolution, real-time concurrent measurements of cardiac autonomic and electrophysiological parameters. Core B will support 5 major endeavors that a fundamental to completion of aims in Projects 1 to 3: Cardiac EP mapping: Advances in analytics for data derived from intra-myocardial multi-pole electrodes, coupled with the deployment of thin-film 2-D form-fit arrays to the epicardium, will define electrical heterogeneities across the border zone areas of the ischemic heart. Complementary in vitro studies can be accomplished in our human heart/Langendorff preparation utilizing either electrical or optical EP mapping. Neurochemical detection: Autonomic assessment will include real-time measurement of regional cardiac neurotransmitter release profiles, leveraging electrochemical cyclic voltammetry (catecholamine) and capacitive immunoprobe (neuropeptide). Such neurochemical measurements can likewise be obtained from vascular compartment to measure trans-cardiac biomarker release profiles. Telemetry: Continuous monitoring for heart rate, temperature and activity in conscious porcine subjects. Chronic Vagal Nerve stimulation: Using FDA approved implantable vagal nerve stimulation devices, animals can be titrated to therapeutic levels of VNS and maintained in that state throughout the treatment phase. Creation of myocardial infarcts: The UCLA Neurocardiology Research Program of Excellence has over a decade of experience in creating a chronic porcine infarct model. This model has been extensively characterized and shown to be comparable to infarcts in patients with ischemic heart disease in both electrophysiological and histopathological characteristics (1). Importantly, this model displays significant neural remodeling at the level of the stellate ganglia, intrinsic cardiac nervous system, and myocardium, making it suitable for the proposed PPG (2, 3). Tasks 3 to 5 are facilitated by the UCLA Neurocardiology Research Program of Excellence having a dedicated large animal aseptic surgical suite designed specifically to support all instrumentation and survival surgery aspects of this PPG and 2 dedicated large animal telemetry rooms capable of monitoring 10 animals at a time.

摘要-科学核心-功能 科学核心B -“功能评估和仪器核心”-的主要目标是优化 生物电子技术，用于高分辨率，实时并行测量心脏自主神经和 电生理参数核心B将支持5项主要工作，这是完成目标的基础 项目1至3：心脏EP标测：心肌内多极数据分析的进展 电极，再加上薄膜2-D形状配合阵列部署到心外膜，将定义电 在缺血心脏的边界区域的异质性。补充的体外研究可以是 在我们的人心脏/Langendorff制备中使用电或光学EP标测完成。 神经化学检测：自主神经评估将包括实时测量局部心脏 神经递质释放曲线，利用电化学循环伏安法（儿茶酚胺）和电容 免疫探针（神经肽）。这种神经化学测量同样可以从血管中获得 测量跨心脏生物标志物释放曲线。遥测：心脏连续监测 在清醒的猪受试者中的心率、体温和活动。慢性迷走神经刺激：使用FDA 在批准的可植入迷走神经刺激装置中，动物可以滴定至VNS的治疗水平， 在整个治疗阶段保持这种状态。心肌梗死的形成：UCLA 卓越的神经心脏病学研究计划在创建慢性猪 梗死模型。该模型已被广泛表征，并显示与患者的梗死相当。 缺血性心脏病的电生理和组织病理学特征（1）。重要的是， 该模型在星状神经节、心脏内神经节和神经纤维节的水平上显示出显著的神经重塑。 系统和心肌，使其适用于所提出的PPG（2，3）。任务3至5由 加州大学洛杉矶分校神经心脏病学卓越研究计划，拥有专用的大型动物无菌手术室 专门设计用于支持本PPG的所有工具和生存手术方面， 大型动物遥测室，可同时监测10只动物。