Electrical therapy for pulseless electrical activity

在治疗心脏骤停的复苏过程中，一个严重的问题是，尽管除颤恢复了有组织的心脏电活动，但心脏功能非常差，以至于很少或根本没有血液被泵出，这种情况称为无脉电活动（PEA）。一种是脉冲刺激，在PEA期间恢复脉冲压力。另一种是DC刺激，以改善慢性心力衰竭期间的功能，这也可能对PEA有益。另一种是DC刺激，以改善慢性心力衰竭期间的功能，这也可能对PEA有益。除了它们的有益作用，这些电刺激也可能有有害的影响，其中最严重的是心律失常的重新开始。这个项目的目标是确定突发和直流刺激的有益和有害影响的机制，电和最佳映射将在动物身上使用，以实现三个具体目标。具体目的1：确定burst和DC刺激对心脏神经活动的影响。这一假设将被验证，即爆发刺激改善心功能的主要机制是通过增加交感神经放电。专项目的2：确定burst和DC刺激对膜极化（Vm）、动作电位（APD）、细胞内钙（Cai/2+）和肌细胞运动的影响。我们将验证DC刺激改善心功能的主要机制是通过在AP平台期去极化Vm，从而延长APD并增加Cai2+。具体目标3：确定突发和直流刺激的有害影响的机制。我们将验证猝发和直流电刺激诱发快速心律失常的机制是电穿孔和Vm临界点的产生。

A serious problem during resuscitation to treat sudden cardiac arrest is that, even though defibrillation restores organized cardiac electrical activity, cardiac function is so poor that little or no blood is pumped, a condition called pulseless electrical activity (PEA). One is burst stimulation to restore a pulse pressure during PEA. The other is DC stimulation to improve function during chronic heart failure, which may also be beneficial during PEA. The other is DC stimulation to improve function during chronic heart failure, which may also be beneficial during PEA. In addition to their beneficial effects, these electrical stimuli may also have detrimental effects, the most serious of which is reinitiation of an arrhythmia. The goal of this project is to determine the mechanism of the beneficial and detrimental effects of burst and DC stimulation Electrical and optimal mapping will be used in animals to accomplish three specific aims. Specific Aim 1: To determine the effect of burst and DC stimulation on cardiac nerve activity. The hypothesis will be tested that the primary mechanism by which burst stimulation improves cardiac function is by increasing sympathetic nerve discharge. Specific Aim 2: To determine the effect of burst and DC stimulation on membrane polarization (Vm), action potential (APD), intracellular calcium (Cai/2+), and myocyte motion. The hypothesis will be tested that the primary mechanism by which DC stimulation improves cardiac function is by depolarizing Vm during the AP plateau, thus prolonging APD and increasing Cai2+. Specific Aim 3: To determine the mechanisms of the detrimental effects of burst and DC stimulation. The hypotheses will be tested that the mechanism for tachyarrhythmia induction by burst and DC stimulation are electroporation and creation of a Vm critical point.