Pulmonary arterial hemodynamics and structure throughout normal development and with arterial stenosis
Abstract/Contents
- Abstract
- Congenital heart defects (CHDs) are structural abnormalities of the heart and the great vessels that affect approximately 1 of 100 children born. Pulmonary artery stenosis is an obstruction which leads to ventilation-perfusion mismatching, right ventricular hypertension, right heart failure and possibly death. These lesions may be difficult to manage, as physicians cannot know a priori whether a particular stenosis should be treated and what the optimal timing for intervention would be. The general purpose of this work has been to quantitatively characterize the developmental effects of a pulmonary artery stenosis on the hemodynamics and structure of the pulmonary arterial system in small animal models. To enable the study of pulmonary arterial hemodynamics, we introduce the application of phase-contrast magnetic resonance imaging (PCMRI) to the pulmonary arteries of rats and quantitatively describe the pulmonary hemodynamic changes that take place with normal postnatal development. We validate the in vivo flow measurements of PCMRI against echocardiography (ultrasound) and fluorescent microspheres and establish the MR technique as consistent and reliable. We describe pulmonary arterial growth trends to consist of a fast growth spurt until adolescence, followed by a continuous yet slower growth until adulthood and show that relative flow to each lung does not change throughout development. To enable the study of the three-dimensional structure of the pulmonary vasculature, we developed new arterial casting, high-resolution micro-Computed Tomography imaging and image analysis techniques that when applied to the normal development of the lung indicate a continual growth of small arterioles [less than]100[Mu]m in lumen size until adulthood. These two novel techniques when applied to the case of a unilateral pulmonary artery stenosis reveal an abrupt reduction of blood flow to the obstructed lung, and an abrupt increase for the contralateral lung. Changes in arterial distensibility relative to pulmonary flow indicate the loss of an initial compensatory mechanism that attempts to maintain the normal homeostatic state but fails at later stages of development. We find that the hypoperfused lung suffers from hypoplasia, as well as severe vascular growth abnormalities of arterial disorganization, loss of vessels, and enlargement of bronchial arteries that result in increased pulmonary vascular resistance. The contralateral lung also exhibits impaired vascular growth due to increased pulmonary flow and pressure. Despite being larger, this lung also suffers from a loss in vessels that under conditions of stress leads to substantial elevation of pulmonary arterial pressures. These results suggest that early intervention in patients with pulmonary artery stenosis may be of utmost importance in halting and reversing such disadvantageous vascular remodelings.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Razavi, Hoda |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Feinstein, Jeffrey A |
| Primary advisor | Taylor, Charles A. (Charles Anthony) |
| Thesis advisor | Feinstein, Jeffrey A |
| Thesis advisor | Taylor, Charles A. (Charles Anthony) |
| Thesis advisor | Pelc, Norbert J |
| Thesis advisor | Rabinovitch, Marlene |
| Advisor | Pelc, Norbert J |
| Advisor | Rabinovitch, Marlene |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Hoda (Hedi) Razavi. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2011. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Hoda Razavi
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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