Modeling of Angiographic Dye Washout From Cerebral Aneurysms Before and After Stenting: An Index for Stent Efficacy

2001 ◽  
Author(s):  
C. Sadasivan ◽  
B. B. Lieber ◽  
D. K. Lopes ◽  
A. J. Ringer ◽  
L. N. Hopkins
Keyword(s):  
Thrombus Formation ◽  
Cerebral Aneurysms ◽  
Parent Artery ◽  
Clinical Tool ◽  
Before And After ◽  
Flow Stasis ◽  
Intracranial Circulation ◽  
Viable Treatment

Abstract The ultimate goal in the treatment of cerebral aneurysms is to exclude them from the intracranial circulation while preserving the parent artery. Recently, in vivo and in vitro experiments and clinical studies demonstrated that endovascular stenting is a significant and viable treatment option for cerebral aneurysms. Stents reduce the mass and momentum transport of blood from the parent artery into the aneurysm and alter both intra-aneurysmal flow and inflow-outflow patterns. The reduction of vorticity and flow stasis within the sac leads to thrombus formation and eventual exclusion of the aneurysm from the circulation. Digital subtraction angiography (DSA) has become an essential clinical tool for the diagnosis and treatment of aneurysms and is an important adjunct to stenting procedures.

Treatment of Cerebral Aneurysms With Flow Divertors: Long Term Results in an In Vivo Model

2007 ◽  
Author(s):  
Chander Sadasivan ◽  
Baruch B. Lieber ◽  
Liliana Cesar ◽  
Jaehoon Seong ◽  
Ajay K. Wakhloo
Keyword(s):  
Thrombus Formation ◽  
Cerebral Aneurysms ◽  
Long Term Results ◽  
In Vivo Model ◽  
Parent Artery ◽  
Momentum Exchange ◽  
Aneurysm Neck ◽  
Flow Stasis

Subarachnoid hemorrhagic stroke is a devastating illness with a 30-day mortality rate of 45% and is mostly caused due to the rupture of an intracranial aneurysm. Although these aneurysms are currently treated surgically by clipping, or, endovascularly by coiling and stent-assisted coiling, the feasibility of successfully treating aneurysms solely by the placement of an intravascular flow-diverting mesh across the aneurysm neck was established more than a decade ago [1]. Flow divertors disrupt the momentum exchange between the parent artery and aneurysm and significantly reduce intraaneurysmal hydrodynamic vorticity. The resultant flow stasis promotes thrombus formation within the aneurysm sac, which eventually matures into fibrotic tissue, leading to the exclusion of the aneurysm from the circulation. With the increased use of stents in the intracranial circulation, cases where coiling is not feasible, or is staged as a secondary procedure, are providing clinical evidence of the successful treatment of aneurysms with stents alone [2,3]. Such reports are sporadic and, moreover, the devices used are not designed to be flow divertors. Methodological evidence of the performance of appropriately designed flow divertors in treating cerebral aneurysms is currently unavailable.

A Novel Method for Excluding Aneurysms From the Cerebral Circulation: Preliminary Results in Rabbits

2009 ◽  
Author(s):  
Baruch B. Lieber ◽  
Mohammad Ali-Aziz Sultan ◽  
Chander Sadasivan ◽  
Brant D. Watson ◽  
Liliana Cesar ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Thrombus Formation ◽  
Cerebral Aneurysms ◽  
Parent Artery ◽  
Momentum Exchange ◽  
Aneurysm Neck ◽  
Novel Method ◽  
Flow Stasis ◽  
Intracranial Circulation ◽  
Flow Diverters

Despite many advances in the treatment of cerebral aneurysms in the last few decades, none of the available methods provide an unequivocal solution for all aneurysm sizes and morphologies. The feasibility of successfully treating aneurysms solely by the placement of an intravascular flow-diverting mesh across the aneurysm neck was established more than a decade ago [1]. Flow diverters disrupt the momentum exchange between the parent artery and aneurysm and significantly reduce intraaneurysmal hydrodynamic vorticity and kinetic energy. The resultant flow stasis promotes thrombus formation within the aneurysm sac, which eventually matures into fibrotic tissue, leading to exclusion of the aneurysm from the circulation. With the increased use of stents in the intracranial circulation, cases where coiling is not feasible, or is staged as a secondary procedure, are providing clinical evidence of the successful treatment of aneurysms with stents alone [2,3]. Methodological evidence of the performance of appropriately designed flow diverters in treating cerebral aneurysms has recently become available in the literature [4,5].

scholarly journals Comparison of the In Vitro Hemodynamic Performance of New Flow Diverters for Bypass of Brain Aneurysms

2012 ◽  
Vol 134 (8) ◽  
Author(s):  
Asher L. Trager ◽  
Chander Sadasivan ◽  
Baruch B. Lieber
Keyword(s):  
Cerebral Aneurysms ◽  
Flow Diverter ◽  
Parent Artery ◽  
New Device ◽  
Design Changes ◽  
Hemodynamic Performance ◽  
Braiding Angle ◽  
Treatment For Cerebral Aneurysms

One possible treatment for cerebral aneurysms is a porous tubular structure, similar to a stent, called a flow diverter. A flow diverter can be placed across the neck of a cerebral aneurysm to induce the cessation of flow and initiate the formation of an intra-aneurysmal thrombus. This excludes the aneurysm from the parent artery and returns the flow of blood to normal. Previous flow diverting devices have been analyzed to determine optimal characteristics, such as braiding angle and wire diameter. From this information, a new optimized device was designed to achieve equivalent hemodynamic performance to the previous best device, but with better longitudinal flexibility to preserve physiological arterial configuration. The new device was tested in vitro in an elastomeric replica of the rabbit elastase induced aneurysm model and is now in the process of being tested in vivo. Particle image velocimetry was utilized to determine the velocity field in the plane of symmetry of the model under pulsatile flow conditions. Device hemodynamic performance indices such as the hydrodynamic circulation were evaluated from the velocity fields. Comparison of these indices with the previous best device and a control shows that the significant design changes of the device did not change its hemodynamic attributes (p > 0.05).

scholarly journals In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-β1

Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3650-3660 ◽  
Author(s):  
Jasimuddin Ahamed ◽  
Nathalie Burg ◽  
Keiji Yoshinaga ◽  
Christin A. Janczak ◽  
Daniel B. Rifkin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Thrombus Formation ◽  
Cell Types ◽  
Transforming Growth Factor Β1 ◽  
Disulfide Exchange ◽  
Before And After ◽  
Tgf Β1

Transforming growth factor-β1 (TGF-β1) has potent physiologic and pathologic effects on a variety of cell types at subnanomolar concentrations. Platelets contain 40 times as much TGF-β1 as other cells and secrete it as an inactive (latent) form in complex with latency-associated peptide (LAP), which is disulfide bonded via Cys33 to latent TGF-β binding protein 1 (LTBP-1). Little is known about how latent TGF-β1 becomes activated in vivo. Here we show that TGF-β1 released from platelets or fibroblasts undergoes dramatic activation when subjected to stirring or shear forces, providing a potential mechanism for physiologic control. Thiol-disulfide exchange appears to contribute to the process based on the effects of thiol-reactive reagents and differences in thiol labeling of TGF-β1 before and after stirring or shear. Activation required the presence of LTBP, as TGF-β1 contained in complex with only LAP could not be activated by stirring when studied as either a recombinant purified protein complex or in the platelet releasates or sera of mice engineered to contain an LAP C33S mutation. Release and activation of latent TGF-β1 in vivo was demonstrated in a mouse model 5 minutes after thrombus formation. These data potentially provide a novel mechanism for in vivo activation of TGF-β1.

Radiolabeled r-Hirudin as a Measure of Thrombin Activity at, or within, the Rabbit Aorta Wall In Vitro and In Vivo

1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet
Keyword(s):  
Rabbit Aorta ◽  
Balloon Injury ◽  
Recombinant Hirudin ◽  
Aorta Wall ◽  
Thrombin Activity ◽  
Before And After ◽  
The Matrix

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Neutralization of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin by Protamine Sulfate in Rats

1986 ◽  
Vol 56 (03) ◽  
pp. 318-322 ◽  
Author(s):  
V Diness ◽  
P B Østergaard
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombus Formation ◽  
Experimental Models ◽  
Protamine Sulfate ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Higher Doses

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.

Surface Modification by Nanobiomaterials for Vascular Tissue Engineering Applications

2020 ◽  
Vol 27 (10) ◽  
pp. 1634-1646 ◽  
Author(s):  
Huey-Shan Hung ◽  
Shan-hui Hsu
Keyword(s):  
Tissue Engineering ◽  
Vascular Tissue ◽  
Thrombus Formation ◽  
Vascular Grafts ◽  
Vascular Tissue Engineering ◽  
Great Success ◽  
Natural Polymers ◽  
Vascular Biomaterials

Treatment of cardiovascular disease has achieved great success using artificial implants, particularly synthetic-polymer made grafts. However, thrombus formation and restenosis are the current clinical problems need to be conquered. New biomaterials, modifying the surface of synthetic vascular grafts, have been created to improve long-term patency for the better hemocompatibility. The vascular biomaterials can be fabricated from synthetic or natural polymers for vascular tissue engineering. Stem cells can be seeded by different techniques into tissue-engineered vascular grafts in vitro and implanted in vivo to repair the vascular tissues. To overcome the thrombogenesis and promote the endothelialization effect, vascular biomaterials employing nanotopography are more bio-mimic to the native tissue made and have been engineered by various approaches such as prepared as a simple surface coating on the vascular biomaterials. It has now become an important and interesting field to find novel approaches to better endothelization of vascular biomaterials. In this article, we focus to review the techniques with better potential improving endothelization and summarize for vascular biomaterial application. This review article will enable the development of biomaterials with a high degree of originality, innovative research on novel techniques for surface fabrication for vascular biomaterials application.

scholarly journals miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB

Cartilage ◽  
2021 ◽  
pp. 194760352110235
Author(s):  
Hongjun Zhang ◽  
Wendi Zheng ◽  
Du Li ◽  
Jia Zheng
Keyword(s):  
Caspase 3 ◽  
Cartilage Tissue ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Knee Cartilage ◽  
Before And After ◽  
Related Proteins ◽  
Human And Mouse

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.

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