research
Robb W. Glenny
Professor of Medicine and of Physiology and Biophysics
MD, MA (computer science)
Faculty Web Page
Last updated: September 27, 2012
Research Focus
The Glenny lab is interested in integrative cardiovascular physiology with a focus on the mechanisms that determine blood flow and ventilation distributions in the lung. Recent work has focused on the geometry of the airway and arterial vascular trees as the principal determinants of regional ventilation and perfusion. These trees have been characterized as fractal structures
Left: Visual map of blood flow to ~2 cm3 lung pieces within a horizontal plane of a supine dog. Note the large heterogeneity of perfusion and the spatial organization with high-flow regions near other high-flow regions and low-flow areas neighboring other low-flow areas. Right: Vascular tree with asymmetrical branching that leads to neighboring regions having similar flows. |
that create spatially heterogeneous blood flow and ventilation distributions yet provide efficient gas exchange through the intimate matching between local ventilation and perfusion. The mechanisms responsible for this close matching are not fully understood. The lab uses a number of imaging tools and comparative animal models to investigate the mechanisms of blood flow and ventilation.
The use of fluorescent microspheres to measure regional ventilation and perfusion were pioneered in the Glenny and Robertson labs (FMRC). The methods can be used across a spectrum of animal sizes from mice to horses. This technique is now being used to investigate the genetic determinants of blood flow distribution in laboratory animals. A recent study in armadillos that produce litters of monozygotic quadruplets, demonstrated that 66% of regional blood flow is genetically determined. The movie below shows the regional blood flow in armadillos from the same litter (A1 and A4) and then compares blood flow between armadillos from different litters (A1 and C4). The color bar at the bottom of the movie represents the relative blood flow to each of the lung regions represented by colored spheres.
Work in the lab is now focusing on extracting airway and vascular trees from lab animals and then using the structure of these trees to model the regional blood flow and ventilation. The lab uses a fluorescent imaging cryomicrotome to obtain transverse images of the lung with simultaneous measures of local blood flow and ventilation in rats. The hypothesis being tested is that the geometries of the airways and vascular trees are correlated and that this shared geometry accounts for the close matching of regional ventilation and perfusion.
A collaborative effort with Pacific Northwest National Laboratory is modeling the deposition of aerosolized particles in laboratory animals and in humans with lung disease. This Bioengineering Research Partnership (BRP) is developing new imaging and modeling tools that will provide new insights into the determinants of aerosol deposition in the lung.
Relevant Publications
Bernard SL, Ewen JR, Barlow CH, Kelly JJ, McKinney S, Frazer DA, and Glenny RW. Highspatial resolution measurements of organ blood flow in small laboratory animals. Am J Physiol Heart Circ Physiol 279: H2043-2052, 2000.
Glenny R, Bernard S, Neradilek B, and Polissar N. Quantifying the genetic influence on mammalian vascular tree structure. Proc Natl Acad Sci U S A 104: 6858-6863, 2007.
Glenny RW. Spatial correlation of regional pulmonary perfusion. J Appl Physiol 72: 2378-2386, 1992.
Glenny RW. Determinants of regional ventilation and blood flow in the lung. Intensive Care Med 35: 1833-1842, 2009.
Glenny RW, Bernard S, and Brinkley M. Validation of fluorescent-labeled microspheres for measurement of regional organ perfusion. J Appl Physiol 74: 2585-2597, 1993.
Glenny RW, Bernard SL, and Robertson HT. Pulmonary blood flow remains fractal down to the level of gas exchange. J Appl Physiol 89: 742-748, 2000.
Glenny RW, Lamm WJ, Albert RK, and Robertson HT. Gravity is a minor determinant of pulmonary blood flow distribution. J Appl Physiol 71: 620-629, 1991.
Glenny RW, Lamm WJ, Bernard SL, An D, Chornuk M, Pool SL, Wagner WW, Jr., Hlastala MP, and Robertson HT. Selected contribution: redistribution of pulmonary perfusion during weightlessness and increased gravity. J Appl Physiol 89: 1239-1248, 2000.
Glenny RW, and Robertson HT. Fractal properties of pulmonary blood flow: characterization of spatial heterogeneity. J Appl Physiol 69: 532-545, 1990.
Robertson HT, Krueger MA, Lamm WJ, and Glenny RW. High-resolution spatial measurements of ventilation-perfusion heterogeneity in rats. J Appl Physiol 108: 1395-1401, 2010.
Active Funding
Funding Source |
Project Title |
Investigator Role |
Funding Dates |
NHLBI RO1 HL073598-01 |
3D Imaging and Computer Modeling of the Respiratory Tract |
Co-I |
7/01/04 – 8/14/15 |
NHLBI R01 HL084550 |
Anti-arrhythmic Effects of Exercise after Implantable Cardioverter Defibrillator |
Co-I |
4/1/07 – 3/31/13 |
NHLBI R21 |
Computer-aided analysis of mechanisms matching ventilation and perfusion |
Co-I |
7/01/11 – 6/30/13 |
Current Mentees
Name |
Degree |
Project |
Malin Ax |
MD, pre-PhD |
Pulmonary blood flow distributions in humans |
Past Mentees
Name |
Degree |
Current title |
Location |
Cindy Dougherty |
PhD |
Professor, Biobehavioral Nursing and Health Systems |
University of Washington |
Johan Petersson |
MD, PhD |
Consultant |
Karolinska Institute |
Sina Gharib |
MD |
Asst. Professor |
University of Washington |
Tony Gerbino |
MD |
Head, Section of Pulmonary Medicine |
Virginia Mason Medical Center, Seattle |
Bill Altemeier |
MD |
Assoc. Professor |
University of Washington |
Michelle Vincent |
PhD |
|
University of Virginia |
Margareta Mure |
MD, PhD |
Assoc. Professor |
Karolinska Institute |