Effect of Pulmonary Vasodilation on the Efficacy of Cardiopulmonary Resuscitation

描述（由申请人提供）：本拨款申请的目的是验证以下假设：心脏骤停后的复苏受到肺血管收缩的限制，在室性颤动或无脉性电活动/心脏骤停后复苏时吸入一氧化氮会增加胸压引起的血流量，提高短期生存率。胸外按压产生全身前向血流量的效果很差，通常估计为正常心输出量的10-25%。然而。问题是，“心肺复苏术中肺血管阻力如何影响向前血流？”的问题一直没有得到复苏研究界的回答。胸外按压时肺循环血流的任何收缩都会限制体循环的血流，而肺血管的扩张会导致胸外按压时血流量的增加。在此基础上，我们提出以下具体目标。具体目标1：继发于心室颤动的心脏骤停。我们假设：缺氧的血液返回肺部导致肺血管阻力增加，从而导致胸外按压时血流量减少。此外，在复苏期间吸入20ppm的一氧化氮，将降低肺血管阻力，增加血流量并提高生存率。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是继发于缺氧和缺氧混合静脉血，这反过来导致胸外按压时血流量的减少。此外，吸入20 ppm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，提高生存率。我们相信，控制肺血管系统将导致复苏方案的范式转变，并导致心脏骤停的存活率增加。

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.