Capillary Perfusion Kinematics in Lungs of Oxygen-Tolerant Rats

Author

Madhavi Ramakrishna, Marquette University

Date of Award

Fall 2009

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical Engineering

First Advisor

Audi, Said H.

Second Advisor

Clough, Anne V.

Third Advisor

Molthen, Robert

Abstract

Motivation:

Prolonged exposure to oxygen at high concentrations (hyperoxia), a common treatment for hypoxemia, is toxic to the lungs. Rats exposed to 85% O₂ for 5-7 days develop tolerance to the otherwise lethal effects of 100% O₂. Elucidating the factors that contribute to this tolerance could further our understanding of the mechanisms of lung O₂ toxicity. Since vascular remodeling involving loss of capillary volume and endothelial surface area has been reported in lungs from rats exposed to 85% O₂ for 7 days, we were interested in evaluating the effect of this hyperoxia model on lung capillary perfusion kinematics. This information is needed for evaluating the effect of this hyperoxia model on the metabolic functions of the pulmonary capillary endothelium, a primary target of O₂ toxicity. Thus, the objective was to evaluate the effect of this hyperoxia model on lung capillary mean transit time (t_c) and distribution of capillary transit times (h_c(t)).

Methods:

Venous concentration versus time outflow curves of fluorescein isothiocyanate labeled dextran (FITC-dex), a vascular indicator, and coenzyme Q1 hydroquinone (CoQ₁H₂), a compound which rapidly equilibrates with lung tissue on passage through the lung, were measured following their bolus injections into the pulmonary artery of isolated lungs from rats exposed to either room air or 85% O₂ for 7 days. A capillary surface area index was estimated by measuring the rate of hydrolysis of the angiotensin converting enzyme substrate N-[3-(2-Furyl) acryloyl]-Phe-Gly-Gly (FAPGG) on passage through each lung. The mean transit time and variance of the measured FITC-dex and CoQ₁H₂ curves were first determined and then used in a mathematical model to estimate and the relative dispersion (RD_c) of h_c(t).

Results:

FITC-dex and CoQ₁H₂ data revealed that hyperoxia decreased lung t_c by 41% and increased RD_c, a measure of the heterogeneity of h_c(t), by 40%. FAPGG data revealed that hyperoxia decreased lung capillary surface area by 56%.

Conclusion:

This study demonstrates the utility of CoQ₁H₂ for evaluating the effect of hyperoxia on capillary perfusion kinematics in intact rat lungs. The results are important for subsequent evaluation of the effect of hyperoxia on the metabolic functions of the pulmonary capillary endothelium.