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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

基本信息

批准号：
7283964
负责人：
Miguel Valderrabano
金额：
$ 20.28万
依托单位：
METHODIST HOSPITAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7283964
关键词：
Biological Calcium Cardiac Cardiac Myocytes Catheters Cell Line Cell membrane Cells Cessation of life Charge Classification Computer Simulation Condition Data Diastole Drug Exposure Electric Countershock Electrodes Exposure to Failure Fluorescent Dyes Goals Heart Heart failure Image Induction of Apoptosis Membrane Mitochondria Modality Monitor Morbidity - disease rate Muscle Cells Neonatal Nuclear Envelope Oryctolagus cuniculus Pain Patients Pattern Phosphatidylserines Physiologic pulse Physiological Prevention Pulse taking Pump Quality of life Rate Rattus Refractory Role Shapes Shock Surface Systole Technology Testing Therapeutic Uses Thinking Tissues Treatment Failure Treatment Protocols United States Ventricular Fibrillation base cost cost effectiveness design electric field hemodynamics improved meter monolayer mortality nanosecond novel response sudden cardiac death two-dimensional voltage

项目摘要

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，只能通过除颤治疗，除颤使用高压场，以疼痛、不适和电池需求为代价取得成功。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。需要新的战略来扩大和加强收缩。超短（ns），高场（MV/m），低能量（microJ）脉冲最近已被证明在非兴奋性细胞中触发各种细胞效应，包括从细胞内储存的钙释放，核膜穿孔，磷脂酰丝氨酸从质膜内层到外层的易位，以及诱导细胞凋亡。这些反应被认为是由产生的大量细胞内电场引起的，这些电场太短而不能充电或不可逆地损伤质膜，质膜被认为对电场是“透明的”。对可兴奋细胞的影响尚未进行系统研究，但初步数据表明，超短，高场电脉冲可以刺激心脏细胞，并可能产生增强的收缩，而能量使用要低得多。本计画的第一个目的是描述纳秒、兆伏特每公尺电脉冲对离体兔心肌细胞的生理效应。将进行脉冲方案与不同生理条件下的反应的系统研究，以描述电压和钙反应及其机制。第二个目的是探讨纳秒，高场脉冲在心脏脉冲传播的影响，在2维心脏基板。我们将首先开发用于将兆伏纳秒脉冲输送到较大心脏组织的电极配置。然后，我们将研究这些脉冲对新生大鼠心肌细胞单层脉冲传播的影响。将评估脉冲对起搏、螺旋波和震颤传播的影响，以确定其作为抗震颤策略的可行性。如果成功，我们的研究将为心脏起搏和除颤的新的低能量技术提供基础，这可以提高数百万心力衰竭患者的生活质量和生存率。