Abstract 187: Constitutively Active Notch4 Elicits Brain Arteriovenous Malformations through Capillary Enlargement

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Tyson N Kim ◽  
Patrick A Murphy ◽  
Lawrence Huang ◽  
Chris B Schaffer ◽  
Rong A Wang
Keyword(s):  
Blood Flow ◽  
Arteriovenous Malformations ◽  
Transgenic Mouse Model ◽  
Capillary Diameter ◽  
Focal Lesions ◽  
Two Photon ◽  
Life Threatening ◽  
Av Malformation ◽  
Positive Feedback Effect ◽  
Constitutively Active

Brain arteriovenous (AV) malformation (BAVM) is characterized by focal lesions of enlarged, tangled vessels that shunt blood from arteries to veins. BAVMs can rupture and cause life-threatening stroke. The origin of BAVM is currently unknown. We have developed a transgenic mouse model of BAVM via endothelial expression of constitutively-active Notch4 (Notch4*). Here, using two-photon excited fluorescence microscopy through chronically-implanted cranial windows, we obtained 4D data on the formation of BAVMs in live animals. We found that BAVMs arose from enlargement of pre-existing capillaries - judged as vessels with capillary diameter and blood flow as well as the absence of smooth muscle coverage. Capillary enlargement began promptly following the start of Notch4* expression and often occurred before increases in blood flow. Supporting the capillary origin of BAVMs, alterations in Notch signaling in endothelial cells of capillaries and veins, but not arteries, affected BAVM formation. Although the initiation of capillary enlargement was widespread, more proximal, lower resistance, AV connections grew into AVMs at the expense of more distal AV connections, by increasing in diameter and blood flow velocity through a positive feedback effect. Our data uncovers a mechanism underlying the focal BAVM formation elicited by a perturbation in gene expression throughout the endothelium.

scholarly journals High-speed volumetric two-photon fluorescence imaging of neurovascular dynamics

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiang Lan Fan ◽  
Jose A. Rivera ◽  
Wei Sun ◽  
John Peterson ◽  
Henry Haeberle ◽  
...  
Keyword(s):  
Blood Flow ◽  
High Speed ◽  
Laser Scanning ◽  
Three Dimensional ◽  
Laser Scanning Microscopy ◽  
Fluorescence Signal ◽  
Imaging Method ◽  
Spatiotemporal Resolution ◽  
Two Photon

AbstractUnderstanding the structure and function of vasculature in the brain requires us to monitor distributed hemodynamics at high spatial and temporal resolution in three-dimensional (3D) volumes in vivo. Currently, a volumetric vasculature imaging method with sub-capillary spatial resolution and blood flow-resolving speed is lacking. Here, using two-photon laser scanning microscopy (TPLSM) with an axially extended Bessel focus, we capture volumetric hemodynamics in the awake mouse brain at a spatiotemporal resolution sufficient for measuring capillary size and blood flow. With Bessel TPLSM, the fluorescence signal of a vessel becomes proportional to its size, which enables convenient intensity-based analysis of vessel dilation and constriction dynamics in large volumes. We observe entrainment of vasodilation and vasoconstriction with pupil diameter and measure 3D blood flow at 99 volumes/second. Demonstrating high-throughput monitoring of hemodynamics in the awake brain, we expect Bessel TPLSM to make broad impacts on neurovasculature research.

scholarly journals Massive haemorrhagic complications of ruptured pulmonary arteriovenous malformations: outcomes from a 12 years’ retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xu Ma ◽  
Bing Jie ◽  
Dong Yu ◽  
Ling-Ling Li ◽  
Sen Jiang
Keyword(s):  
Arteriovenous Malformations ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Pulmonary Arteriovenous Malformations ◽  
Imaging Data ◽  
Peripheral Lung ◽  
Life Threatening ◽  
The Mean

Abstract Background The life-threatening haemorrhagic complications of pulmonary arteriovenous malformations (PAVMs) are extremely rare, and only described in isolated cases. This study was designed to comprehensively investigate management of ruptured PAVMs. Methods We retrospectively assessed clinical and imaging data of ruptured PAVMs to summarize incidence, clinical characteristics, and outcomes following embolisation between January 2008 and January 2021. Results Eighteen of 406 (4.4%) patients with PAVMs developed haemorrhagic complications. Twelve of 18 patients were clinically diagnosed with hereditary haemorrhagic telangiectasia (HHT). Haemorrhagic complications occurred with no clear trigger in all cases. Eight of 18 patients (44.4%) were initially misdiagnosed or had undergone early ineffective treatment. 28 lesions were detected, with 89.3% of them located in peripheral lung. Computed tomography angiography (CTA) showed indirect signs to indicate ruptured PAVMs in all cases. Lower haemoglobin concentrations were associated with the diameter of afferent arteries in the ruptured lesions. Successful embolotherapy was achieved in all cases. After embolotherapy, arterial oxygen saturation improved and bleeding was controlled (P < 0.05). The mean follow-up time was 3.2 ± 2.5 years (range, 7 months to 10 years). Conclusions Life threatening haemorrhagic complications of PAVMs are rare, they usually occur without a trigger and can be easily misdiagnosed. HHT and larger size of afferent arteries are major risk factors of these complications. CTA is a useful tool for diagnosis and therapeutic guidance for ruptured PAVMs. Embolotherapy is an effective therapy for this life-threatening complication.

scholarly journals Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gautier Follain ◽  
Naël Osmani ◽  
Valentin Gensbittel ◽  
Nandini Asokan ◽  
Annabel Larnicol ◽  
...  
Keyword(s):  
Blood Flow ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Metastatic Progression ◽  
Metastatic Dissemination ◽  
Secondary Tumors ◽  
Flow Profiles ◽  
Endothelial Response ◽  
Life Threatening

AbstractTumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.

In vivo microvascular structural and functional consequences of muscle length changes

1997 ◽  
Vol 272 (5) ◽  
pp. H2107-H2114 ◽  
Author(s):  
D. C. Poole ◽  
T. I. Musch ◽  
C. A. Kindig
Keyword(s):  
Blood Flow ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Oxygen Delivery ◽  
Sarcomere Length ◽  
Flow Dynamics ◽  
Capillary Diameter ◽  
Luminal Diameter ◽  
Length Changes

As muscles are stretched, blood flow and oxygen delivery are compromised, and consequently muscle function is impaired. We tested the hypothesis that the structural microvascular sequellae associated with muscle extension in vivo would impair capillary red blood cell hemodynamics. We developed an intravital spinotrapezius preparation that facilitated direct on-line measurement and alteration of sarcomere length simultaneously with determination of capillary geometry and red blood cell flow dynamics. The range of spinotrapezius sarcomere lengths achievable in vivo was 2.17 +/- 0.05 to 3.13 +/- 0.11 microns. Capillary tortuosity decreased systematically with increases of sarcomere length up to 2.6 microns, at which point most capillaries appeared to be highly oriented along the fiber longitudinal axis. Further increases in sarcomere length above this value reduced mean capillary diameter from 5.61 +/- 0.03 microns at 2.4-2.6 microns sarcomere length to 4.12 +/- 0.05 microns at 3.2-3.4 microns sarcomere length. Over the range of physiological sarcomere lengths, bulk blood flow (radioactive microspheres) decreased approximately 40% from 24.3 +/- 7.5 to 14.5 +/- 4.6 ml.100 g-1.min-1. The proportion of continuously perfused capillaries, i.e., those with continuous flow throughout the 60-s observation period, decreased from 95.9 +/- 0.6% at the shortest sarcomere lengths to 56.5 +/- 0.7% at the longest sarcomere lengths and was correlated significantly with the reduced capillary diameter (r = 0.711, P < 0.01; n = 18). We conclude that alterations in capillary geometry and luminal diameter consequent to increased muscle sarcomere length are associated with a reduction in mean capillary red blood cell velocity and a greater proportion of capillaries in which red blood cell flow is stopped or intermittent. Thus not only does muscle stretching reduce bulk blood (and oxygen) delivery, it also alters capillary red blood cell flow dynamics, which may further impair blood-tissue oxygen exchange.

scholarly journals Ovarian Torsion Presentation, Treatment and Iatrogenic Surgical Management

2021 ◽  
pp. 70-76
Author(s):  
Sheema Sabahath ◽  
Hussain Salah AL Sinan ◽  
Asalah Tariq Alsaigh ◽  
Rawan AlSalamah AlFadhli ◽  
Tahani Salman Al Mansour ◽  
...  
Keyword(s):  
Blood Flow ◽  
Abdominal Pain ◽  
Side Effects ◽  
Adverse Events ◽  
Surgical Intervention ◽  
Clinical Manifestations ◽  
Ovarian Torsion ◽  
Adult Females ◽  
Uterine Ligaments ◽  
Life Threatening

Ovarian torsion is among the gynecological life-threatening conditions that may require urgent surgical intervention among the appearance of clinical manifestations. The most common clinical manifestations include severe abdominal pain, nausea extending to vomiting. The ovarian torsion is not limited to children only. However, it can also occur in adult females, either pregnant or non-pregnant. The etiology of the disease tends to be related to the weakness of the uterine ligaments or malpositioning of it due to known and unknown causes. Despite that, the surgical intervention is needed to release the torsion. Sometimes, it can lead to adverse events or side effects such as decreased blood flow to the surrounding structures. Which by role may lead to unpleasant complications and clinical manifestations of hemorrhage and shock. In this article, we reviewed the topic of ovarian torsion from different aspects, including the definition, causes, clinical evaluation, and clinical management and its common complications.

Uncontrolled bleeding during tooth extraction from an undiagnosed arteriovenous malformation

2021 ◽  
Vol 14 (8) ◽  
pp. e236983
Author(s):  
Kumar Nilesh ◽  
Swenil Shah ◽  
Amol Gautam ◽  
Sagar Thorat
Keyword(s):  
Arteriovenous Malformations ◽  
Tooth Extraction ◽  
Severe Bleeding ◽  
Space Management ◽  
Vascular Morphogenesis ◽  
Vascular Flow ◽  
Life Threatening ◽  
Surgical Manipulation ◽  
Uncontrolled Bleeding ◽  
Adult Female Patient

Arteriovenous malformations (AVMs) are rare congenital disorders of vascular morphogenesis. These lesions are characterised by high vascular flow with risk of severe bleeding from accidental trauma or surgical manipulation. Although infrequent, potentially life-threatening and fatal oral bleeding has been reported during extraction of tooth associated with AVM. This paper presents a case of uncontrolled bleeding in an adult female patient undergoing mandibular anterior tooth extraction. The bleeding was related to undiagnosed soft tissue AVM in gingivobuccal space. Management of the case with review of previously reported similar cases is presented.

scholarly journals Cerebral Arteriovenous Malformations with Associated Arterial Aneurysms: Hemodynamic and Therapeutic Considerations

1988 ◽  
Vol 15 (2) ◽  
pp. 130-134 ◽  
Author(s):  
Douglas Kondziolka ◽  
Bruce J. Nixon ◽  
Pierre Lasjaunias ◽  
Pierre Lasjaunias ◽  
William S. Tucker ◽  
...  
Keyword(s):  
Blood Flow ◽  
Arteriovenous Malformation ◽  
Endovascular Treatment ◽  
Arteriovenous Malformations ◽  
Local Blood Flow ◽  
Cerebral Arteriovenous Malformations ◽  
Regional Hemodynamics ◽  
The Common ◽  
Arterial Aneurysms ◽  
Therapeutic Considerations

ABSTRACT:The common vascular anomalies of cerebral aneurysm and arteriovenous malformation may exist independently, or together as part of a closely related hemodynamic pairing. Resection or embolization of an AVM may be followed by a decrease in local blood flow, and lead to regression of a suitably situated proximal aneurysm. However, aneurysms located outside the angioarchitecture of the AVM, which remain flow-unrelated to the malformation, will likely not regress, and may in fact enlarge. Two cases are presented which demonstrate these vascular relationships, in order to better understand the regional hemodynamics of these anomalies prior to surgical or endovascular treatment planning.

scholarly journals Lenvatinib-Induced Tumor-Related Hemorrhages in Patients with Large Hepatocellular Carcinomas

Oncology ◽  
2020 ◽  
pp. 1-6 ◽  
Author(s):  
Sawako Uchida-Kobayashi ◽  
Ken Kageyama ◽  
Akira Yamamoto ◽  
Hiroko Ikenaga ◽  
Kanako Yoshida ◽  
...  
Keyword(s):  
Blood Flow ◽  
Tumor Diameter ◽  
Careful Attention ◽  
Single Center ◽  
Tumor Blood Flow ◽  
Hepatocellular Carcinomas ◽  
Single Center Study ◽  
Life Threatening ◽  
Maximum Tumor Diameter ◽  
Center Study

<b><i>Introduction:</i></b> Lenvatinib has been approved as a systemic therapy for patients with unresectable hepatocellular carcinoma (HCC). We recently experienced lenvatinib-induced tumor-related hemorrhage in patients with HCC. The full details of tumor-related hemorrhage as a lenvatinib-related adverse event have not been elucidated. <b><i>Methods:</i></b> This was a retrospective single-center study that enrolled consecutive patients treated with lenvatinib for unresectable HCC from April 2018 to February 2020. <b><i>Results:</i></b> Sixty-eight consecutive patients were enrolled in this study. Among them, 5 cases developed intraperitoneal or intratumoral hemorrhages. The patients with hemorrhage had larger tumors (maximum tumor size, 97.5 ± 46.4 and 38.2 ± 28.8 mm, respectively; <i>p</i> = 0.009) than the patients without hemorrhage. The dosing period of lenvatinib (median, 3 and 93 days, respectively; <i>p</i> &#x3c; 0.001) and the survival time from initial administration of lenvatinib (median, 77 and 495 days, respectively; <i>p</i> &#x3c; 0.001) of the patients with hemorrhage were shorter than those of the patients without hemorrhage. Especially, in 4 cases with large HCCs (maximum tumor diameter was &#x3e;90 mm), tumor hemorrhage with vascular lake-like phenomenon was evident, although most tumor blood flow was suppressed. <b><i>Discussion/Conclusion:</i></b> It becomes clear that lenvatinib treatment brings about tumor-related hemorrhages despite rapid suppression of tumor blood flow. We speculate that lenvatinib quickly blocks the feeding circulation, resulting in tumor hemorrhage by necrosis. Clinicians should pay careful attention to the development of life-threatening hemorrhages when treating large HCCs with lenvatinib.

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