Core B: Functional Assessment & Instrumentation

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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.