Regional Hypoxic Pulmonary Vasoconstriction

描述(由申请人提供)：通过通风和灌流的紧密匹配进行有效的气体交换。这种区域匹配是由缺氧性肺血管收缩(HPV)促进的。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中区域性HPV(HPVR)的区域变异。使用荧光微球，我们将在活体肺中测定1.7cm3小块中的VA/Q、肺泡PO2和PCO2。暴露在不同程度的低氧下将提供每一块的HPVR图谱。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。HPV的异质性将使用三种肺标本来探索，每种肺标本都有不同的方法学优势：整个动物准备、分离的肺(一个肺缺氧)和分离的灌流肺。具体目标将量化的作用：1)VA/Q异质性导致局部PO2(PRO2)和局部PRCO2的变化；2)局部血流的初始大小可能影响HPVR；3)区域通气性；4)肺动脉压升高；5)神经影响可能起作用；6)NO释放的空间差异；7)内皮素释放或受体密度的空间差异；7)平滑肌体积和分布；以及8)暴露于HPV的时间。研究结果将为更详细地了解导致HPVR异质性的局部和细胞机制以及哺乳动物肺部疾病的发展机制提供更详细的信息。

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.