A Rational Engineering Design Approach to Minimizing the Off-Target Effects of Baroreceptor Activation Therapy

最小化压力感受器激活疗法的脱靶效应的合理工程设计方法

• 批准号: 10653217
• 负责人: Kip A Ludwig
• 金额: $ 62.44万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653217
• 关键词: 3-Dimensional; Acute; Address; Adult; Affect; Anatomy; Applications Grants; Baroreflex; Biomedical Engineering; Blood Pressure; Breathing; Cadaver; Cardiac; Carotid Body; Cervical; Chemoreceptors; Chronic; Clinical; Computer Models; Controlled Clinical Trials; Data; EFRAC; Electric Stimulation; Electrodes; Exhibits; FDA approved; Family suidae; Fiber; Geometry; Goals; Heart Rate; Heart failure; Histologic; Hospitalization; Human; Hypertension; Image; Imaging Techniques; In Situ; Larynx; Life Expectancy; Measurement; Mediating; Medical; Methods; Modeling; Motor; Motor Pathways; Muscle; Muscle Contraction; Nerve; Nerve Fibers; Neural Pathways; Neuroanatomy; Outcome; Pathway interactions; Patients; Performance; Pharmacological Treatment; Population; Postural adjustments; Pressoreceptors; Process; Quality of life; Receptor Activation; Recurrence; Research Project Grants; Resistance; Sampling; Skeletal muscle structure of neck; Source; Stretching; Testing; Therapeutic; Tissues; Translating; Treatment Efficacy; blood perfusion; carotid sinus; clinical application; design; engineering design; experimental study; human model; improved; neural; neuroregulation; novel; porcine model; pre-clinical; respiratory; response; side effect; targeted treatment; therapy design; translational therapeutics; vagus nerve stimulation

Abstract Despite improvements in medical management, hypertension still affects >25% of adults, and 20 to 30% of them are resistant to pharmacological treatment. Similarly, heart failure patients with reduced ejection fraction continue to exhibit dramatically reduced life expectancy, frequent hospitalization, and overall poor quality of life. Chronic electrical stimulation of the baroreflex at the carotid sinus—known as baroreflex activation therapy (BAT)—is FDA-approved to mitigate the marked sympathetic activation associated with both hypertension and heart failure. BAT was demonstrated in multiple controlled clinical trials to produce sustained significant improvements in both hypertension and heart failure outcomes in patients non-responsive to traditional medical management; however, the therapy is limited by side effects. We propose an integrated approach to mitigate side effects and thereby improve the therapeutic efficacy of BAT. We seek to determine the functional neuroanatomy responsible for the side effects of BAT and to use these data to design and test approaches for more effective BAT neural interfaces. These optimized designs will expand the therapeutic window between baroreceptor activation and limiting off-target effects. The outcomes of this project will produce an optimized BAT interface design that could be quickly translated to address a clear clinical need. In addition, we will provide a needed framework for incorporation of local neural and tissue anatomy—which govern therapy-limiting side effects—into the neural interface design process that can be readily applied to myriad neuromodulation therapy targets.

抽象的 尽管医疗管理有所改善，但高血压仍影响> 25％的成年人，而20％至30％ 它们对药物治疗有抵抗力。同样，射血分数减少的心力衰竭患者 继续存在大大降低预期寿命，频繁住院和整体质量差 生活。颈动脉鼻窦上的压力反射的慢性电刺激（称为aroreflex激活疗法） （BAT） - 是FDA批准的，以减轻与高血压和高血压相关的明显交感神经激活 心脏衰竭。在多个受控临床试验中证明了BAT，以产生持续的显着性 对传统医学无反应的患者的高血压和心力衰竭结果的改善 管理;但是，该疗法受副作用的限制。我们提出了一种综合方法来减轻 副作用，从而提高蝙蝠的治疗效率。 我们试图确定负责蝙蝠副作用的功能性神经解剖学并使用这些功能 设计和测试方法的数据，以实现更有效的BAT神经界面。这些优化的设计将 在压力感受器激活和限制脱靶效应之间扩展理论窗口。结果 这个项目将产生优化的蝙蝠界面设计，可以快速翻译以解决 明确的临床需求。此外，我们将为当地神经和组织保险提供一个必要的框架 解剖结构（控制限制治疗的副作用）在神经界面设计过程中可能是 容易应用于众多神经调节疗法靶标。