skip to main content

Title: Stenting-induced Vasa Vasorum compression and subsequent flow resistance: a finite element study
Vascular stenting is a common intervention for the treatment for atherosclerotic plaques. However, stenting still has a significant rate of restenosis caused by intimal hyperplasia formation. In this study, we evaluate whether stent overexpansion leads to Vasa Vasorum (VV) compression, which may contribute to vascular wall hypoxia and restenosis. An idealized multilayered fibroatheroma model including Vasa Vasorum was expanded by three coronary stent designs up to a 1.3:1 stent/artery luminal diameter ratio (exp1.1, exp1.2, exp1.3) using a finite element analysis approach. Following Poiseuille’s law for elliptical sections, the fold increase in flow resistance was calculated based on VV compression in the Intima (Int), Media (Med) and Adventitia (Adv). The VV beneath the plaque experiences the smallest degree of compression, while the opposite wall regions are highly affected by stent overexpansion. The highest compressions for Adv, Med and Int at exp1.1 are 60.7, 65.9, 72.3%, at exp1.2 are 62.1, 67.3, 73.5% and at expp1.3 are 63.2, 68.7, 74.8%. The consequent fold increase in resistance to flow for Adv, Med and Int at exp1.1 is 3.3, 4.4, 6.6, at exp1.2 is 3.5, 4.7, 7.2 and at exp1.3 is 3.8, 5.1, 7.9. Stent overexpansion induces significant VV compression, especially in the Intima and more » Media layers, in agreement with previously observed Media necrosis and loss in elasticity after stenting. The observed steep increase in flow resistance suggests the blood flow and associated oxygen delivery would drop up to five times in the Media and almost eight in the Intima, which may lead to intimal hyperplasia and restenosis « less
Authors:
; ; ;
Award ID(s):
1662970
Publication Date:
NSF-PAR ID:
10189036
Journal Name:
Biomechanics and Modeling in Mechanobiology
ISSN:
1617-7959
Sponsoring Org:
National Science Foundation
More Like this
  1. Atherosclerosis and vascular disease of larger arteries are often associated with hypoxia within the layers of the vascular wall. In this review, we begin with a brief overview of the molecular changes in vascular cells associated with hypoxia and then emphasize the transport mechanisms that bring oxygen to cells within the vascular wall. We focus on fluid mechanical factors that control oxygen transport from lumenal blood flow to the intima and inner media layers of the artery, and solid mechanical factors that influence oxygen transport to the adventitia and outer media via the wall's microvascular system—the vasa vasorum (VV). Many cardiovascular risk factors are associated with VV compression that reduces VV perfusion and oxygenation. Dysfunctional VV neovascularization in response to hypoxia contributes to plaque inflammation and growth. Disturbed blood flow in vascular bifurcations and curvatures leads to reduced oxygen transport from blood to the inner layers of the wall and contributes to the development of atherosclerotic plaques in these regions. Recent studies have shown that hypoxia-inducible factor-1α (HIF-1α), a critical transcription factor associated with hypoxia, is also activated in disturbed flow by a mechanism that is independent of hypoxia. A final section of the review emphasizes hypoxia in vascular stentingmore »that is used to enlarge vessels occluded by plaques. Stenting can compress the VV leading to hypoxia and associated intimal hyperplasia. To enhance oxygen transport during stenting, new stent designs with helical centrelines have been developed to increase blood phase oxygen transport rates and reduce intimal hyperplasia. Further study of the mechanisms controlling hypoxia in the artery wall may contribute to the development of therapeutic strategies for vascular diseases.« less
  2. Stent thrombosis (ST) carries a high risk of myocardial infarction and death. Lack of endothelial coverage is an important prognostic indicator of ST after stenting. While stent strut thickness is a critical factor in ST, a mechanistic understanding of its effect is limited and the role of haemodynamics is unclear. Endothelialization was tested using a wound-healing assay and five different stent strut models ranging in height between 50 and 150 µm for circular arc (CA) and rectangular (RT) geometries and a control without struts. Under static conditions, all stent strut surfaces were completely endothelialized. Reversing pulsatile disturbed flow caused full endothelialization, except for the stent strut surfaces of the 100 and 150 µm RT geometries, while fully antegrade pulsatile undisturbed flow with a higher mean wall shear stress caused only the control and the 50 µm CA geometries to be fully endothelialized. Modest streamlining and decrease in height of the stent struts improved endothelial coverage of the peri-strut and stent strut surfaces in a haemodynamics dependent manner. This study highlights the impact of the stent strut height (thickness) and geometry (shape) on the local haemodynamics, modulating reendothelialization after stenting, an important factor in reducing the risk of stent thrombosis.
  3. Objective: Using a mouse model of Eln (elastin) insufficiency that spontaneously develops neointima in the ascending aorta, we sought to understand the origin and phenotypic heterogeneity of smooth muscle cells (SMCs) contributing to intimal hyperplasia. We were also interested in exploring how vascular cells adapt to the absence of Eln. Approach and Results: We used single-cell sequencing together with lineage-specific cell labeling to identify neointimal cell populations in a noninjury, genetic model of neointimal formation. Inactivating Eln production in vascular SMCs results in rapid intimal hyperplasia around breaks in the ascending aorta’s internal elastic lamina. Using lineage-specific Cre drivers to both lineage mark and inactivate Eln expression in the secondary heart field and neural crest aortic SMCs, we found that cells with a secondary heart field lineage are significant contributors to neointima formation. We also identified a small population of secondary heart field-derived SMCs underneath and adjacent to the internal elastic lamina. Within the neointima of SMC-Eln knockout mice, 2 unique SMC populations were identified that are transcriptionally different from other SMCs. While these cells had a distinct gene signature, they expressed several genes identified in other studies of neointimal lesions, suggesting that some mechanisms underlying neointima formation in Elnmore »insufficiency are shared with adult vessel injury models. Conclusions: These results highlight the unique developmental origin and transcriptional signature of cells contributing to neointima in the ascending aorta. Our findings also show that the absence of Eln, or changes in elastic fiber integrity, influences the SMC biological niche in ways that lead to altered cell phenotypes.« less
  4. Introduction: Recent reports have raised concern about the risk of vessel wall injury (VWI) when pulling out current laser-cut stent retrievers during active strut apposition to the vessel walls.1-4 Development of braided thrombectomy-assist devices for use in conjunction with aspiration systems may be gentler (lower radial force) and more optimized for vessel diameters seen in proximal LVOs and distal LVOs. Methods: Bench testing of radial force (RF) was performed using a radial compression station. The total radial force (RF) in Newtons (N) generated in vessel diameters (d) (Range 2.25 to 3mm) seen in proximal LVOs (~M1), and vessel diameters (d) (Range 1.5 to 2.24mm) seen in distal LVOs (~M2) was measured. Radial Force of less than or equal to 1N was grouped as “low” and radial force greater than 1N was grouped as “high” for this analysis. Results: The total radial force (RF) of all laser-cut stent retrievers (with distal outer diameter OD in mm) studied namely Solitaire Platinum (6.0), Solitaire 2 (4.0), Trevo ProVue (4.0), Baby Trevo (3.0), Capture L (3.0) were all higher in the M2 vessels (>1N) compared to M1 vessels (<1N), whereas the total radial force (RF) of the braided thrombectomy-assist devices namely SHELTER® Retriever (6.0)more »were uniformly low in both the M1 (<1N) and M2 (<1N) vessels. Conclusion: Choosing a stent retriever with lower OD does not translate to lower radial force. As a result, sizing of stent retrievers and thrombectomy-assist devices to target vessels should not only factor the OD of the devices but also the total radial force in the target vessel diameter. Novel braided thrombectomy-assist devices for use in conjunction with aspiration systems have lower radial force compared to existing laser-cut stent retrievers in the M1 and M2 vessel diameters. Further studies in-vivo need to assess the impact of lower radial force on minimizing VWI. Funding Source: This study was funded in part by a research grant (NSF Award: 1819491; PI: Vallabh Janardhan, MD) from the National Science Foundation (NSF). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Conference Proceeding: This paper was presented in part at the 2018 Annual Meeting of the Society of Vascular & Interventional Neurology (SVIN), November 14-17, 2018 in San Diego, CA« less
  5. Background: Recent reports have raised concern about the risk of vessel wall injury (VWI) when pulling out current laser-cut stent retrievers with active strut apposition to the vessel walls. Development of braided stroke thrombectomy-assist devices for use in conjunction with aspiration systems may be gentler in the internal carotid (ICA) and basilar vessels (with regards to radial force) compared to existing laser-cut stent retrievers. Methods: Radial force (RF) bench testing was performed using a radial compression station (Blockwise Engineering, Phoenix, AZ). The average total radial force (RF) in Newtons (N) generated (average of 3 readings) in vessel diameters (d) (Range 3.25 to 4.00mm) seen in proximal LVOs of the anterior circulation (such as in the internal carotid artery - ICA), and vessel diameters (d) (Range 2.50 to 3.25mm) seen in the posterior circulation (such as in the basilar artery - BA) was measured. The Solitaire Platinum Revascularization Device (Medtronic, Irvine, CA) was used as the predicate device. All thrombectomy and thrombectomy-assist devices were compared in terms of the RF being higher or lower (%) to the predicate device. Results: The results of the radial force testing are shown in the table below. The total radial force (RF) of the SHELTER®more »Retriever (part of Insera System, Insera Therapeutics, Inc., Dallas, TX), a braided thrombectomy-assist device is significantly lower (@ d=2.5mm: 58%) than the predicate device (@ d=2.5mm: 100%) and other laser-cut stent retrievers (@ d=2.5mm: 103% to 152%). Thrombectomy devices with lower OD had higher radial forces than larger devices. Conclusion: Novel braided stroke thrombectomy-assist devices for use in conjunction with aspiration systems have lower radial force compared to existing laser-cut stent retrievers in the ICA and BA vessel diameters. Further studies in-vivo need to assess the impact of lower radial force on minimizing VWI. Funding Source: This study was funded in part by a research grant (NSF Award: 1819491; PI: Vallabh Janardhan, MD) from the National Science Foundation (NSF). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Conference Proceeding: This paper was presented in part at the 2018 Annual Meeting of the Society of Vascular & Interventional Neurology (SVIN), November 14-17, 2018 in San Diego, CA« less