Quantitative models of the rat pulmonary arterial tree morphometry applied to hypoxia-induced arterial remodeling

Abstract

Little is known about the constituent hemodynamic consequences of structural changes that occur in the pulmonary arteries during the onset and progression of pulmonary arterial remodeling. Many disease processes are known to be responsible for vascular remodeling that leads to pulmonary arterial hypertension, cor pulmonale, and death. Histology has been the primary tool for evaluating pulmonary remodeling, but it does not provide information on intact vascular structure or the vessel mechanical properties. This study is an extension of our previous work in which we developed an alternative imaging technique to evaluate pulmonary arterial structure. The lungs from Sprague-Dawley rats were removed, perfusion analysis was performed on the isolated lungs, and then an X-ray contrast agent was used to fill the arterial network for imaging. The lungs were scanned over a range of intravascular pressures by volumetric micro-computed tomography, and the arterial morphometry was mapped and measured in the reconstructed isotropic volumes. A quantitative assessment of hemodynamic, structural, and biomechanical differences between rats exposed for 21 days to hypoxia (10% O(2)) or normoxia (21.0% O(2)) was performed. One metric, the normalized distensibility of the arteries, is significantly (P < 0.001) larger [0.025 +/- 0.0011 (SE) mmHg(-1)] (n = 9) in normoxic rats compared with hypoxic [0.015 +/- 0.00077 (SE) mmHg(-1)] (n = 9). The results of the study show that these models can be applied to the Sprague-Dawley rat data and, specifically, can be used to differentiate between the hypoxic and the control groups.

Lung Circulation Modeling: Status and Prospect

“…5,[55][56]57,58,59 An abundance of histological data on cellular composition, reactivity data from large isolated vessels, and changes in cellular metabolism in response to hypoxia and other models of pulmonary hypertension have been published. 53,55,56,[59][60]61,62 However, complete understanding of the mechanisms and consequences of vascular remodeling requires knowledge of the etiology and impact of pulmonary hypertension on the longitudinal distribution of pulmonary vascular resistance, lumenal morphology, and branching patterns of the pulmonary arterial tree.…”

“…Thus, mathematical models have been developed that integrate three-dimensional representations of the tree into the appropriate hemodynamic context to understand and predict flow and pressure distributions within the arterial tree. 4,63,64 These models can be used to predict the impact of pathologies, such as vessel drop out, decreased arterial distensibility, or both, to identify which treatment modalities are likely to have the most positive impact. …”

“…10,66,67 it is prudent to use concepts related to fractal-like structures, such as self-consistency, to simplify data analysis and modeling calculations. To this end, the principal pathway was defined as the main pulmonary arterial trunk and its immediate daughter branches, 5,63,68,69 as shown in Fig. 6.…”

“…Thus, in a statistical sense, the principal pathway of a selfconsistent tree would contain all of the information needed to rebuild the entire pulmonary arterial tree. Since rat pulmonary arterial trees have been shown to be self-consistent, 5,63,69 the task of measuring all the vessels in the pulmonary tree is reduced to measuring only the vessels along the main pulmonary trunk and the inlet diameter of its immediate daughter branches. Application of these simplifying conventions provides a means of summarizing the global morphometric and mechanical properties of the vascular tree from a reduced set of measurements.…”

“…Thus, there has been much investigation devoted to understanding structurefunction relationships in the pulmonary vasculature and how these relationships are affected by physiological adaptation and lung injury and disease. [1][2]3,4,5,6,7,8,9,10,11 Mathematical modeling has played an important role in understanding the hemodynamics of the lungs. Several deterministic models of the pulmonary vascular bed have been developed as tools for understanding the functional implications of the measured geometry and mechanical behavior of the components of the pulmonary vascular bed.…”