Effect of Pulmonary Vasodilation on the Efficacy of Cardiopulmonary Resuscitation

描述(由申请者提供)：这项资助申请的目的是检验这样一种假设，即从心脏骤停中复苏受到肺血管收缩的限制，以及在心室颤动或无脉搏电活动/心脏骤停复苏期间吸入一氧化氮将增加胸部按压引起的血流量，并改善短期存活率。胸部按压在产生前向全身血流量方面的效果很差，通常估计为正常心输出量的10%-25%。现在还不行。问题是，在心肺复苏期间，肺血管阻力是如何影响前向血流的？还没有得到复苏研究界的回答。在胸部按压时，肺循环中的任何血流收缩都会限制体循环中的血液流动，而肺血管的扩张应该会导致胸部按压时的血流量增加。基于这些思路，我们提出了以下具体目标。具体目标1：继发于室颤的心脏骤停。我们假设：氧合不良的血液返回肺部会导致肺血管阻力增加，进而导致胸部按压时血流量减少。此外，在复苏期间吸入20ppm的一氧化氮，将降低肺血管阻力，增加血流量，提高存活率。具体目标2：继发于呼吸骤停的心脏骤停。我们假设，肺血管阻力的增加继发于低氧和低氧混合静脉血，这反过来会导致胸部按压时血流量的减少。此外，吸入20ppm的一氧化氮将降低肺血管阻力，改善胸部按压时的血液流动，并提高存活率。我们认为，操纵肺血管系统将导致复苏方案的范式转变，并增加心脏骤停的存活率。 公共卫生相关性：在美国，院前环境中的心脏骤停是主要的死亡原因。在心脏可以再次收缩之前，胸部按压是唯一被接受的提供血液流动的方法。我们假设，肺内动脉的收缩限制了胸部按压产生的血流量，通过吸入将药物输送到肺部的药物扩张这些血管将改善胸部按压产生的血流量，并最终提高心脏骤停的存活率。

DESCRIPTION (provided by applicant): The goal of this grant application is to test the hypothesis that resuscitation from cardiac arrest is limited by pulmonary vasoconstriction and that inhalation of nitric oxide during resuscitation from either ventricular fibrillation or pulseless electrical activity/asystole cardiac arrest will increase blood flow caused by chest compressions and improve short-term survival. The efficacy of chest compressions in generating forward systemic blood flow is poor, often estimated at 10-25% of normal cardiac output. Yet. the question, 'How does pulmonary vascular resistance affect forward blood flow during CPR?' has not been been answered by the resuscitation research community. Any constriction to blood flow in the pulmonary circulation during chest compressions will limit blood flow in the systemic circulation and dilation of the pulmonary vessels should lead to an increase in blood flow during chest compressions. Based on these ideas, we propose the following specific aims. Specific Aim 1: Cardiac arrest secondary to ventricular fibrillation. We hypothesize: that poorly oxygenated blood returning to the lungs causes an increase in pulmonary vascular resistance which in turn causes a decrease in blood flow during chest compressions. Further, delivery of inhaled nitric oxide, 20 ppm, during resuscitation, will decrease pulmonary vascular resistance, increase blood flow and improve survival. Specific Aim 2: Cardiac arrest secondary to respiratory arrest. We hypothesize that an increase in pulmonary vascular resistance occurs secondary to both hypoxia and poorly oxygenated mixed venous blood which in turn causes a decrease in blood flow during chest compressions. Further, inhaled nitric oxide, 20 ppm, will decrease pulmonary vascular resistance, improve blood flow during chest compressions and improve survival. We believe that manipulating the pulmonary vasculature will lead to a paradigm shift in resuscitation protocols and lead to an increased survival from cardiac arrest. PUBLIC HEALTH RELEVANCE: Cardiac Arrest in the pre-hospital setting is a leading cause of death in the United States. Chest compressions are the only accepted means of providing blood flow until the heart can be made to contract again. We hypothesize that constriction of the arteries in the lung limit the blood flow generated by chest compressions and that dilating these blood vessels with drugs delivered to the lungs by inhalation will improve blood flow generated by chest compressions and ultimately improve survival from cardiac arrest.