Redistribution of pulmonary perfusion during bronchoconstriction in asthma

描述(申请人提供)：在美国有1700多万人患有哮喘，而且发病率还在上升。对哮喘的研究主要集中在呼吸道上，然而，对哮喘发作期间局部肺血流灌注的变化知之甚少。我们实验室最近使用正电子发射断层扫描(PET)功能成像的研究首次表明，在乙酰甲胆碱诱导的支气管收缩期间，自发呼吸的哮喘患者发生了显著的血流再分配，远离低通气区的斑块。这项研究的长期目标是了解哮喘患者支气管收缩过程中局部血流再分布的机制和影响因素。本项目要检验的主要假设是：1)远离通风缺陷的血流重新分配主要是由缺氧性肺血管收缩引起的，而不仅仅是乙酰胆碱引起的支气管收缩的伪影；2)对于给定程度的收缩刺激，远离通风不良区域的血流重新分配在仰卧位将不如俯卧位有效，因为重力往往会与缺氧性血管收缩的效果相反。这些假说将使用最先进的区域灌注和通风的PET-CT功能成像进行验证，具体目的如下：1)评估在乙酰甲胆碱诱导的支气管收缩(SA-1A)过程中，通过呼吸高氧浓度消除低氧刺激是否会钝化血流的重新分布。2)评估在其他支气管收缩刺激诱导的支气管收缩过程中是否发生类似的血流再分配，如果是，评估缺氧性肺血管收缩在多大程度上参与了这种再分配(SA-1B)。3)比较俯卧位和仰卧位在高氧浓度(SA-2)下呼吸时远离通风不良区域的血流再分配的幅度。这项研究旨在提高我们对哮喘发作期间肺部血流和气流匹配机制的理解，以及这些机制在哮喘发作恢复过程中的变化。了解这一重要的肺功能可能会改善哮喘的治疗，并可能减少与哮喘相关的死亡。每二十个美国人中就有一个患有哮喘。在哮喘发作期间，肺试图匹配气流和血流量，以保持氧气向重要器官的输送。哮喘死亡的原因之一可能是肺执行这一重要功能的能力受损。这项研究将研究哮喘发作期间气流和血流匹配的机制，以便开发更好的治疗方法来预防哮喘死亡。

DESCRIPTION (provided by applicant): Asthma affects over 17 million people in the United States and the incidence is rising. Research in asthma has focused on the airways, however, little is known about how regional pulmonary perfusion changes during an asthma attack. Recent studies from our lab using positron emission tomography (PET) functional imaging have shown for the first time that dramatic perfusion redistribution, away from patchy areas of low ventilation, take place in spontaneously breathing human subjects with asthma during methacholine-induced bronchoconstriction. The long-term objective of this research is to understand the mechanisms of, and factors that modify, the regional perfusion redistribution during bronchoconstriction in asthma. The main hypotheses to be tested in this project are 1) The redistribution of perfusion away from ventilation defects is primarily caused by hypoxic pulmonary vasoconstriction and is not solely an artifact of methacholine-induced bronchoconstriction and 2) For a given degree of constrictive stimulus, the redistribution of perfusion away from poorly ventilated areas will be less effective in the supine than in the prone position because gravitational forces would tend to oppose the effectiveness of hypoxic vasoconstriction. These hypotheses will be tested using state-of-the-art PET-CT functional imaging of regional perfusion and ventilation with the following specific aims: 1) Assess whether elimination of the hypoxic stimulus by breathing a high oxygen concentration blunts the redistribution of perfusion during methacholine-induced bronchoconstriction (SA-1A). 2) Assess whether a similar perfusion redistribution occurs during bronchoconstriction induced by other bronchoconstrictive stimuli and, if so, evaluate the extent to which hypoxic pulmonary vasoconstriction is involved in that redistribution (SA-1B). 3) Compare the magnitude of redistribution of perfusion away from poorly ventilated regions in the prone and supine positions breathing with and without a high oxygen concentration (SA-2). This research is designed to improve our understanding of the mechanisms that match blood flow and airflow in the lungs during an asthma attack and how these change during recovery from an asthma attack. Knowledge of this important lung function may lead to improved asthma therapy and possibly reduce asthma-related deaths. Asthma affects one out of every twenty Americans. During an asthma attack, the lung tries to match airflow and blood flow in order to maintain oxygen delivery to vital organs. One of the causes of asthma deaths may be impairment in the ability of the lung to perform this important function. This research will study the mechanisms for matching airflow and blood flow during an asthma attack so that better treatments can be developed to prevent asthma deaths.