The long-term objective of this project is to obtain a better understanding of the properties of the pulmonary blood-gas barrier and, in particular, the conditions under which stress failure occurs resulting in pulmonary edema and hemorrhage. Pulmonary edema is a common, serious condition and elucidation of its mechanisms is therefore of great importance. The first group of Specific Aims is devoted to a better understanding of the factors responsible for the strength of the blood-gas barrier. Since it is now recognized that two distinct mechanisms are responsible for increasing stress in the barrier, namely increased capillary transmural pressure, and the forces resulting from lung inflation, we plan to compare the structure of the barrier in animals that expand their lungs with animals that have a virtually rigid lung, that is the bird. We shall also measure the minimal thickness of the blood-gas barrier by morphometric techniques and relate this to the breaking stress of type IV collagen. The second Specific Aim is devoted to failure of the blood-gas barrier. We shall look at the lungs of ducks, geese and chickens where the barrier is known to be extremely thin, and recent work shows a surprising degree of bleeding into the alveolar spaces. A final Specific Aim is devoted to a related project, namely the vulnerability of pleural capillaries under conditions of negative pressure breathing. Our work to date on this project has been very productive. The identification of stress failure has clarified various aspects of human pathology such as the mechanism of high-altitude pulmonary edema, and the damage to pulmonary capillaries caused by high states of lung inflation. We also discovered the mechanism of exercise-induced pulmonary hemorrhage in racehorses. In addition, at the more basic level, this research is devoted to a fundamental biological dilemma of the lung, namely how the blood-gas barrier combines extreme thinness with immense strength. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL060968-05A1
Application #
6873400
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Denholm, Elizabeth M
Project Start
2000-03-17
Project End
2007-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
5
Fiscal Year
2005
Total Cost
$268,990
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
West, John B (2011) Comparative physiology of the pulmonary circulation. Compr Physiol 1:1525-39
West, John B (2011) Causes of and compensations for hypoxemia and hypercapnia. Compr Physiol 1:1541-53
West, John B (2011) History of respiratory gas exchange. Compr Physiol 1:1509-23
West, John B; Fu, Zhenxing; Deerinck, Thomas J et al. (2010) Structure-function studies of blood and air capillaries in chicken lung using 3D electron microscopy. Respir Physiol Neurobiol 170:202-9
Maina, J N; West, J B; Orgeig, S et al. (2010) Recent advances into understanding some aspects of the structure and function of mammalian and avian lungs. Physiol Biochem Zool 83:792-807
West, John B (2010) Did differences in mitochondrial properties influence the evolution of avian and mammalian lungs? Am J Physiol Lung Cell Mol Physiol 299:L595-6
West, John B; Fu, Zhenxing; Gu, Yusu et al. (2010) Pulmonary artery pressure responses to increased cardiac output in chickens with raised metabolic rate. Comp Biochem Physiol A Mol Integr Physiol 156:430-5
West, John B (2009) Comparative physiology of the pulmonary blood-gas barrier: the unique avian solution. Am J Physiol Regul Integr Comp Physiol 297:R1625-34
Watson, Rebecca R; Fu, Zhenxing; West, John B (2008) Minimal distensibility of pulmonary capillaries in avian lungs compared with mammalian lungs. Respir Physiol Neurobiol 160:208-14
West, John B (2008) Ibn al-Nafis, the pulmonary circulation, and the Islamic Golden Age. J Appl Physiol 105:1877-80

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