Evaluating the impact of mammalian coronary collateral flow during fetal and adult stages
Abstract/Contents
- Abstract
- Collateral arteries are a vessel subtype that bridges two artery branches, forming a natural bypass that can deliver blood flow downstream of an occlusion. These bridges in the human heart are associated with better outcomes during coronary artery disease. We recently found that their rapid development in neonates supports heart regeneration, while the non-regenerative adult heart displays slow and minimal collateralization. Thus, inducing robust collateral artery networks could serve as viable treatment for cardiac ischemia, but reaching this goal requires increased knowledge of developmental mechanisms and functional capabilities. Here, we use whole-organ imaging and 3D computational fluid dynamics (CFD) modeling to identify the spatial architecture of and predict blood flow through collaterals in neonate and adult hearts. We found that neonatal collaterals are more numerous, larger in diameter, and, even when similar in size/number, are predicted to more effectively re-perfuse an occluded coronary network when compared to those in adults. CFD analysis revealed that collaterals perform better in neonates because of de-creased differential pressures along the coronary artery tree. Furthermore, testing of various collateral configurations indicated that larger, more proximal collaterals are more beneficial than many smaller ones, identifying a target architecture for future therapeutic interventions. Morphometric analysis revealed how the coronary artery network expands during postnatal growth. Vessel diameters do not scale with cardiac muscle growth. Instead, the coronary tree expands solely by adding additional branches of a set length, a burst of which occurs during murine puberty. Finally, we compared mouse structural and functional data to human hearts. Surprisingly, fetal human hearts possessed a very large number of small, but mature, smooth muscle cell covered collaterals while angiogram data indicated adult patients with chronic coronary occlusions contained at least two. Comparing size ratios with modeled mouse data suggested low re-perfusion capabilities of the embryonic collaterals but higher functional benefits of those in diseased adults. Comparison of fetal guinea pig and human collaterals suggests that the collaterals in the fetal guinea pig stabilize due to increased pressure loads, while the collaterals in the fetal human are slowly pruned as the pressure load lessens. Our unique interdisciplinary approach allowed us to quantify the functional significance and maintenance of collateral arteries during heart regeneration and repair--a critical step towards realizing their therapeutic potential.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Anbazhakan, Suhaas |
|---|---|
| Degree supervisor | Marsden, Alison (Alison Leslie), 1976- |
| Degree supervisor | Red-Horse, Kristy |
| Thesis advisor | Marsden, Alison (Alison Leslie), 1976- |
| Thesis advisor | Red-Horse, Kristy |
| Thesis advisor | Ennis, Daniel B |
| Degree committee member | Ennis, Daniel B |
| Associated with | Stanford University, Department of Bioengineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Suhaas Anbazhakan. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/xw497pr3382 |
Access conditions
- Copyright
- © 2022 by Suhaas Anbazhakan
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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