Regional Hypoxic Pulmonary Vasoconstriction

说明（由申请人提供）：通过通风和灌注的紧密匹配实现高效的气体交换。缺氧肺血管收缩（HPV）促进了这种区域匹配。虽然全球HPV一直是呼吸系统研究的重点，但我们已经确定并量化了哺乳动物肺部区域HPV （HPVR）的区域差异。我们将利用荧光微球测定体内肺1.7 cm3小片内的VA /Q、肺泡PO2和PCO2。暴露于不同程度的缺氧将提供每个片段的HPVR概况。我们将评估哺乳动物肺中hpv异质性的潜在机制。我们将研究猪，一种与人类有强烈HPV反应的动物。HPV的异质性将使用三种肺制剂进行探讨，每种肺制剂都有不同的方法学优势：全动物准备，分离肺（一个肺缺氧）和分离的，灌注的肺。具体目标将量化：1)VA /Q异质性导致区域PO2 （PRO2）和区域PRCO2的变化；2)局部血流初始大小可能影响HPVR；3)区域通风；4)肺动脉压升高；5)神经影响可能起作用；6) NO释放的空间变异；7)内皮素释放或受体密度的空间变异；7)平滑肌的体积和分布；8)暴露于HPV的时间。该研究的结果将提供对哺乳动物肺部hpv异质性和疾病发展机制的局部和细胞机制的更详细的了解。

DESCRIPTION (provided by applicant): Efficient gas exchange occurs through tight matching of ventilation and perfusion. This regional matching is facilitated by hypoxic pulmonary vasoconstriction (HPV). While global HPV has been a focus of respiratory research, we have identified and quantified regional variation in regional HPV (HPVR) in the mammalian lung. Using florescent microspheres, we will determine VA /Q, alveolar PO2 and PCO2 within small 1.7 cm3 pieces in the in vivo lung. Exposure to graded levels of hypoxia will provide HPVR profiles for each piece. We will evaluate potential mechanisms for heterogeneity of HPVR in the mammalian lung. We will study the pig, an animal with strong HPV response similar to the human. Heterogeneity of HPV will be explored using three lung preparations each having various methodological strengths: The whole animal prep, separated lung (one lung hypoxia) and the isolated, perfused lung. Specific aims will quantify the roles of: 1) VA /Q heterogeneity causing variation of regional PO2 (PRO2) and regional PRCO2; 2) initial magnitude of regional blood flow may influence HPVR; 3) regional ventilation; 4) elevation of pulmonary artery pressure; 5) neural influences may play a role; 6) spatial variation in NO release; 7) spatial variation in endothelin release or receptor density; 7) smooth muscle volume and distribution; and 8) time of exposure to HPV. The results of the research will provide a more detailed understanding of the local and cellular mechanisms responsible for HPVR heterogeneity and mechanisms of development of disease in the mammalian lung.