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].

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.

scholarly journals Postprocedural, midterm, and long-term results of cerebral aneurysms treated with flow-diverter devices: 7-year experience at a single center

2017 ◽  
Vol 42 (6) ◽  
pp. E3 ◽  
Author(s):  
Francesco Briganti ◽  
Giuseppe Leone ◽  
Luigi Cirillo ◽  
Oreste de Divitiis ◽  
Domenico Solari ◽  
...  
Keyword(s):  
Cerebral Aneurysms ◽  
Flow Diverter ◽  
Long Term Results ◽  
Parent Artery ◽  
Long Term Follow Up ◽  
Ischemic Complications ◽  
Flow Diverter Devices ◽  
Aneurysm Occlusion

OBJECTIVEFlow diversion has emerged as a viable treatment option for selected intracranial aneurysms and recently has been gaining traction. The aim of this study was to evaluate the safety and effectiveness of flow-diverter devices (FDDs) over a long-term follow-up period.METHODSThe authors retrospectively reviewed all cerebral aneurysm cases that had been admitted to the Division of Neurosurgery of the Università degli Studi di Napoli between November 2008 and November 2015 and treated with an FDD. The records of 60 patients (48 females and 12 males) harboring 69 cerebral aneurysms were analyzed. The study end points were angiographic evidence of complete aneurysm occlusion, recanalization rate, occlusion of the parent artery, and clinical and radiological evidence of brain ischemia. The occlusion rate was evaluated according to the O’Kelly-Marotta (OKM) Scale for flow diversion, based on the degree of filling (A, total filling; B, subtotal filling; C, entry remnant; D, no filling). Postprocedural, midterm, and long-term results were strictly analyzed.RESULTSComplete occlusion (OKM D) was achieved in 63 (91%) of 69 aneurysms, partial occlusion (OKM C) in 4 (6%), occlusion of the parent artery in 2 (3%). Intraprocedural technical complications occurred in 3 patients (5%). Postprocedural complications occurred in 6 patients (10%), without neurological deficits. At the 12-month follow-up, 3 patients (5%) experienced asymptomatic cerebral infarction. No further complications were observed at later follow-up evaluations (> 24 months). There were no reports of any delayed aneurysm rupture, subarachnoid or intraparenchymal hemorrhage, ischemic complications, or procedure- or device-related deaths.CONCLUSIONSEndovascular treatment with an FDD is a safe treatment for unruptured cerebral aneurysms, resulting in a high rate of occlusion. In the present study, the authors observed effective and stable aneurysm occlusion, even at the long-term follow-up. Data in this study also suggest that ischemic complications can occur at a later stage, particularly at 12–18 months. On the other hand, no other ischemic or hemorrhagic complications occurred beyond 24 months.

scholarly journals Catestatin prevents endothelial inflammation and promotes thrombus resolution in acute pulmonary embolism in mice

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Hua Chen ◽  
Dongxia Liu ◽  
Lan Ge ◽  
Tao Wang ◽  
Zhenzhen Ma ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Acute Pulmonary Embolism ◽  
Thrombus Formation ◽  
Vascular Dysfunction ◽  
In Vivo Model ◽  
Protective Effects ◽  
Inhibitory Peptide ◽  
Endothelial Inflammation

AbstractCatestatin (CTS), a catecholamine-release inhibitory peptide, exerts pleiotropic cardiac protective effects. Pulmonary embolism caused by deep vein thrombosis involving vascular dysfunction. The present study aims to investigate the effects of CTS on thrombus formation that may inhibit the development of pulmonary embolism and its potential pathway. Acute pulmonary embolism (APE) model was developed as an in vivo model. The effects of CTS on mice with APE were examined. Human pulmonary artery endothelial cells (HPAECs) were pretreated with CTS before thrombin stimulation, and endothelial inflammation and underlying mechanisms were evaluated in vitro. That plasma CTS level was decreased in APE mice, while the number of platelets was significantly increased. The decreased circulating CTS level negatively associated with the number of platelets. CTS administration increased the survival rate of APE mice and protected against microvascular thrombosis in lung. APE-induced the increase in platelets number and plasma von Willebrand factor (VWF) were inhibited by CTS. Platelets from CTS-treated APE mice showed impaired agonist-induced platelets aggregation and spreading. CTS also ameliorated APE-induced the systemic inflammatory response. In in vivo study, thrombin-induced the increase in inflammation, TLR-4 expression and p38 phosphorylation were abrogated by CTS in HPAECs. Furthermore, TLR-4 overexpression inhibited the effect of CTS on VWF release and inflammation in HPAECs. Collectively, CTS increases thrombus resolution by attenuating endothelial inflammation at partially via inhibiting TLR-4-p38 pathway. The present study may provide a novel approach for anti-thrombosis.

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 Abciximab (ReoPro) Dosing Strategy for the Management of Acute Intraprocedural Thromboembolic Complications during Pipeline Flow Diversion Treatment of Intracranial Aneurysms

2018 ◽  
Vol 7 (5) ◽  
pp. 218-232 ◽  
Author(s):  
Li-Mei Lin ◽  
Bowen Jiang ◽  
Jessica K. Campos ◽  
Narlin B. Beaty ◽  
Matthew T. Bender ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Thrombus Formation ◽  
Cerebral Aneurysms ◽  
Flow Diversion ◽  
Thromboembolic Complications ◽  
Limited Experience ◽  
Residual Thrombus ◽  
Dosing Strategy

Background: Flow diversion with the Pipeline embolization device (PED) is an effective neuro­endovascular method and increasingly accepted for the treatment of cerebral aneurysms. Acute in situ thrombosis is a known complication of PED procedures. There is limited experience in the flow diversion literature on the use of abciximab (ReoPro) for the management of acute thrombus formation in PED cases. Methods: Data were collected retrospectively on patients who received intra-arterial (IA) ReoPro with or without subsequent intravenous (IV) infusion during PED flow diversion treatment of intracranial aneurysms. Results: A total of 30 cases in patients with a mean age of 56.7 years (range 36–84) and a mean aneurysm size of 8.6 mm (range 2–25) were identified to have intraprocedural thromboembolic complications during PED treatment. IA ReoPro was administered in all cases, with 20 cases receiving increments of 5-mg boluses and 10 cases receiving a 0.125 mg/kg IA bolus (half cardiac dosing). Complete or partial recanalization was achieved in 100% of the cases. IV ReoPro infusion at 0.125 μg/kg/min for 12 h was administered postprocedurally in 22 cases with a residual thrombus. Postprocedurally, 18 patients were transitioned from clopidogrel (Plavix) to prasugrel (Effient). The majority of the cases (23/30; 77%) were discharged home. Periprocedural intracranial hemorrhage was noted in 2 cases (7%) and radiographic infarct was noted in 4 cases (13%), with an overall mortality of 0% at the time of initial discharge. Clinical follow-up was available for 28/30 patients. The average duration of follow-up was 11.7 months, at which time 23/28 (82%) of the patients had a modified Rankin Scale score of 0. Conclusions: IA ReoPro administration is an effective and safe rescue strategy for the management of acute intraprocedural thromboembolic complications during PED treatment. Using a dosing strategy of either 5-mg increments or a 0.125 mg/kg IA bolus (half cardiac dosing) can provide high rates of recanalization with low rates of hemorrhagic complications and long-term morbidity.

scholarly journals Use of 5-fluorouracil to analyze the effect of macrophage inflammatory protein-1 alpha on long-term reconstituting stem cells in vivo

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1497-1504 ◽  
Author(s):  
VF Quesniaux ◽  
GJ Graham ◽  
I Pragnell ◽  
D Donaldson ◽  
SD Wolpe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Inhibitory Effect ◽  
In Vivo Model ◽  
Hematopoietic Progenitors ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Abstract A macrophage-derived inhibitor of early hematopoietic progenitors (colony-forming unit-spleen, CFU-A) called stem cell inhibitor was found to be identical to macrophage inflammatory protein-1 alpha (MIP-1 alpha). We investigated the effect of MIP-1 alpha on the earliest stem cells that sustain long-term hematopoiesis in vivo in a competitive bone marrow repopulation assay. Because long-term reconstituting (LTR) stem cells are normally quiescent, an in vivo model was first developed in which they are triggered to cycle. A first 5-fluorouracil (5-FU) injection was used to eliminate later progenitors, causing the LTR stem cells, which are normally resistant to 5-FU, to enter the cell cycle and become sensitive to a second 5-FU injection administered 5 days later. Human MIP-1 alpha administered from day 0 to 7 was unable to prevent the depletion of the LTR stem cells by the second 5-FU treatment, as observed on day 7 in this model, suggesting that the LTR stem cells were not prevented from being triggered into cycle despite the MIP-1 alpha treatment. However, the MIP-1 alpha protocol used here did substantially decrease the number of more mature hematopoietic progenitors (granulocyte-macrophage colony-forming cells [CFC], burst- forming unit-erythroid, CFCmulti, and preCFCmulti) recovered in the bone marrow shortly after a single 5-FU injection. In vitro, MIP-1 alpha had no inhibitory effect on the ability of these progenitors to form colonies. This study confirms the in vivo inhibitory effect of MIP- 1 alpha on subpopulations of hematopoietic progenitors that are activated in myelodepressed animals. However, MIP-1 alpha had no effect on the long-term reconstituting stem cells in vivo under conditions in which it effectively reduced all later progenitors.

scholarly journals Long-Term Results and Follow-Up Examinations after Endovascular Embolization for Unruptured Cerebral Aneurysms

2019 ◽  
Vol 40 (7) ◽  
pp. 1191-1196 ◽  
Author(s):  
T. Murakami ◽  
T. Nishida ◽  
K. Asai ◽  
Y. Kadono ◽  
H. Nakamura ◽  
...  
Keyword(s):  
Cerebral Aneurysms ◽  
Endovascular Embolization ◽  
Long Term Results ◽  
Unruptured Cerebral Aneurysms

scholarly journals In Vivo Testing of a Magnetically Suspended Centrifugal Pump Designed for Long-Term Use

1997 ◽  
Vol 20 (10) ◽  
pp. 562-569 ◽  
Author(s):  
T. Yamada ◽  
K. Nishimura ◽  
T. Akamatsu ◽  
T. Tsukiya ◽  
C.H. Park ◽  
...  
Keyword(s):  
Centrifugal Pump ◽  
Rotational Speed ◽  
Thrombus Formation ◽  
Current Mode ◽  
Left Ventricular ◽  
Centrifugal Pumps ◽  
Motor Current ◽  
Magnetically Suspended Centrifugal Pump

The life of currently-available centrifugal pumps is limited to no more than three days. As a magnetically suspended centrifugal pump (MSCP) contains no shaft or seal, it could be expected to have a longer life expectancy. The MSCP was evaluated in a chronic animal model using eight adult sheep. Left ventricular assist with the MSCP was instituted between the left atrium and the descending aorta. The flow rates ranged from 2.5 to 6.0 L/min. The duration of the experiments ranged from 14 to 60 days. No mechanical failure occurred. The plasma free hemoglobin levels remained within an acceptable range (3-19 mg/dL). No reduction in the counts of red blood cells or platelets was observed. Thrombus formation within the MSCP was recognized in one pump. The main reason for termination was thromboembolism derived from the circuits. Three types of regulation methods (constant rotational speed, constant motor current, and controlled motor current) were also investigated. Regulation by a constant motor current mode altered the pressure-flow (P-Q) characteristics, and thereby, a steadier pump flow was obtained compared with regulation in the constant rotational speed mode. Moreover, the controlled motor current mode can change the P-Q relationship. These results demonstrate that the MSCP is a promising device for long-term use.

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