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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL069868-02
Application #
6739643
Study Section
Respiratory Physiology Study Section (RESP)
Program Officer
Croxton, Thomas
Project Start
2003-05-01
Project End
2007-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
2
Fiscal Year
2004
Total Cost
$379,000
Indirect Cost
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Hopkins, Susan R; Kleinsasser, Axel; Bernard, Susan et al. (2007) Hypoxia has a greater effect than exercise on the redistribution of pulmonary blood flow in swine. J Appl Physiol 103:2112-9
Tsang, John Y C; Lamm, Wayne J E; Neradilek, Blazej et al. (2007) Endothelin receptor blockade does not improve hypoxemia following acute pulmonary thromboembolism. J Appl Physiol 102:762-71
Tsang, John Y C; Lamm, Wayne J E; Starr, Ian R et al. (2005) Spatial pattern of ventilation-perfusion mismatch following acute pulmonary thromboembolism in pigs. J Appl Physiol 98:1862-8