Regional Hypoxic Pulmonary Vasoconstriction

描述（申请人提供）：通过通风和灌注的紧密匹配来进行有效的气体交换。缺氧性肺血管收缩（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焦点，但我们已经确定并量化了哺乳动物肺中局部HPV（HPVR）的区域变化。使用荧光微球，我们将在体内肺中测定1.7 cm 3小块内的VA /Q、肺泡PO 2和PCO 2。暴露于分级缺氧水平将提供每件的HPVR曲线。我们将评估哺乳动物肺中HPVR异质性的潜在机制。我们将研究猪，一种与人类相似的具有强烈HPV反应的动物。将使用三种肺制备物探索HPV的异质性，每种肺制备物具有不同的方法学优势：整个动物制备物、分离的肺（一个肺缺氧）和分离的灌注肺。具体目标将量化以下因素的作用：1）VA /Q异质性导致局部PO 2（PRO 2）和局部PRCO 2的变化; 2）局部血流量的初始大小可能影响HPVR; 3）局部通气; 4）肺动脉压升高; 5）神经影响可能发挥作用; 6）NO释放的空间变化; 7）内皮素释放或受体密度的空间变化; 7）平滑肌体积和分布;和8）暴露于HPV的时间。该研究的结果将提供对HPVR异质性的局部和细胞机制以及哺乳动物肺部疾病发展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.