Nanosecond megavolt pulse technology for cardiac stimulation and defibrillation

用于心脏刺激和除颤的纳秒兆伏脉冲技术

• 批准号: 7129551
• 负责人: Miguel Valderrabano
• 金额: $ 24.51万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7129551
• 关键词: bioengineering /biomedical engineering; biomedical equipment development; calcium; calcium flux; calcium indicator; catheterization; clinical biomedical equipment; computer simulation; electric countershock heart resuscitation; electrical potential; electrodes; electrostimulus; fluorescent dye /probe; heart contraction; heart failure; infant animal; intracellular; laboratory rabbit; laboratory rat; molecular /cellular imaging; muscle cells; nanotechnology; technology /technique development; tissue /cell culture; ventricular fibrillation

DESCRIPTION (provided by applicant): Our long-term objective is to establish the feasibility of ultrashort, high field electrical pulses as a mechanism of cardiac stimulation, contraction enhancement, and defibrillation. The major modes of death in heart failure are sudden cardiac death (SCD) and refractory pump failure. Ventricular fibrillation (VF) is the leading cause of SCD and can only be treated by defibrillation, which uses high voltage fields and succeeds at the cost of pain, discomfort and battery demands. Pump failure treatment with positive inotropic agents leads to hemodynamic improvements but causes long-term increased mortality. New strategies to defibrillate and enhance contraction are needed. Ultrashort (ns), high-field (MV/m), low energy (microJ) pulses have recently been shown to trigger a variety of cellular effects in nonexcitable cells, including calcium release from intracellular stores, poration of the nuclear membrane, translocation of phosphatidylserine from the inner to the outer layer of the plasma membrane, and induction of apoptosis. These responses are thought to be caused by the substantial intracellular electric fields generated, which are too brief to charge or irreversibly damage the plasma membrane, deemed to be "transparent" to the fields. Effects on excitable cells have not been systematically studied, but preliminary data suggests that ultra-short, high-field electric pulses can excite cardiac cells and potentially generate enhanced contraction with much lower energy use by. The first aim of this project is to delineate the physiological effects of nanosecond, megavolt-per-meter electric pulses in isolated rabbit myocytes. Systematic studies of pulse regimens vs. responses under different physiological conditions will be performed to delineate the voltage and calcium responses and their mechanisms. The second aim is to explore the effects of nanosecond, high-field pulses in cardiac impulse propagation in 2-dimensional cardiac substrates. We will first develop electrode configurations for delivery of megavolt nanosecond pulses to larger cardiac tissues. We will then study the effects of these pulses on impulse propagation in neonatal rat myocyte monolayers. Effects of pulses on paced, spiral wave and fibrillatory propagation will be assessed to establish their feasibility as an antifibrillatory strategy. If successful, our studies would provide a basis for a new, low energy technology for cardiac pacing, and defibrillation which could improve the quality of life and survival of millions of patients with heart failure.

描述（由申请人提供）：我们的长期目标是确定超短高场电脉冲作为心脏刺激、收缩增强和除颤机制的可行性。心力衰竭的主要死亡方式是心源性猝死（SCD）和难治性泵衰竭。心室颤动 (VF) 是 SCD 的主要原因，只能通过除颤来治疗，除颤使用高压场，但以疼痛、不适和电池需求为代价取得了成功。使用正性肌力药物治疗泵衰竭可改善血流动力学，但会导致长期死亡率增加。需要新的除颤和增强收缩策略。超短 (ns)、高场 (MV/m)、低能量 (microJ) 脉冲最近已被证明可在非兴奋性细胞中触发多种细胞效应，包括细胞内储存的钙释放、核膜穿孔、核细胞易位等。磷脂酰丝氨酸从质膜内层向外层延伸，诱导细胞凋亡。这些反应被认为是由产生的大量细胞内电场引起的，这些电场太短而无法充电或不可逆地损坏被认为对电场“透明”的质膜。对可兴奋细胞的影响尚未得到系统研究，但初步数据表明，超短、高场电脉冲可以兴奋心肌细胞，并可能以低得多的能量消耗产生增强的收缩。该项目的首要目标是描述纳秒、兆伏每米电脉冲对离体兔肌细胞的生理效应。将对不同生理条件下的脉冲方案与反应进行系统研究，以描述电压和钙反应及其机制。第二个目标是探索纳秒高场脉冲对二维心脏基质中心脏脉冲传播的影响。我们将首先开发电极配置，用于将兆伏纳秒脉冲传递到更大的心脏组织。然后我们将研究这些脉冲对新生大鼠肌细胞单层脉冲传播的影响。将评估脉冲对起搏波、螺旋波和纤颤传播的影响，以确定其作为抗纤颤策略的可行性。如果成功，我们的研究将为用于心脏起搏和除颤的新型低能量技术奠定基础，从而改善数百万心力衰竭患者的生活质量和生存率。