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）：我们的长期目标是建立超短，高场电脉冲的可行性，作为心脏刺激，收缩增强和除颤的机制。心力衰竭的主要死亡方式是心脏猝死（SCD）和难治性泵衰竭。心室纤颤（VF）是SCD的主要原因，只能通过除颤，它使用高压场，并以疼痛，不适和电池需求为代价而成功。用阳性肌力剂治疗泵衰竭会导致血液动力学改善，但导致长期死亡率增加。需要进行除颤和增强收缩的新策略。最近已证明超短色（NS），高场（MV/m），低能量（MicroJ）脉冲会触发各种细胞中的各种细胞作用，包括从细胞内存储中钙释放，核膜的钙化，磷脂酰甲酯的易位，从磷酸甲酯的易位，从磷脂内部层到垂体膜的内部层，磷脂的内部层，磷灰膜的外层和apoct a apopt and Indoct of Apopt of Apopt of Apopt of apopt of Apopt of Apopt of Apopt of a apopt and Indoct sisosis。这些反应被认为是由产生的大量细胞内电场引起的，这些电场太短暂了，无法充电或不可逆转地损坏质膜，被认为是对田地“透明”的。对激发细胞的影响尚未系统地研究，但是初步数据表明，超短而高场的电脉冲可以激发心脏细胞，并有可能通过较低的能量使用而产生增强的收缩。该项目的第一个目的是描述孤立的兔肌细胞中纳秒，每米电脉冲的生理效应。在不同生理条件下的脉冲方案与反应的系统研究将进行描述电压和钙反应及其机制。第二个目的是探索二维心脏底物中纳秒高场脉冲在心脏脉冲传播中的影响。我们将首先开发电极构型，用于将巨型纳秒脉冲传递到较大的心脏组织。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。将评估脉冲对节奏，螺旋波和支架传播的影响，以确定其可行性作为抗颤音策略。如果成功的话，我们的研究将为心脏起搏的新型低能技术提供基础，以及除颤，从而可以改善数百万心脏衰竭患者的生活质量和生存。