Medium-sized Arterioles Research Articles

Livedoid vasculopathy.

Livedoid vasculopathy is a painful thrombo-occlusive vascular disorder characterized by spontaneous thrombosis in medium-size arterioles, which causes localized hypoxia and skin ulceration. As livedoid vasculopathy is rare, case reports are the primary means of expanding collective knowledge about its presentation and response to various therapies.

Sneddon Syndrome, About a Case Report and Literature Review

Sneddon's syndrome is a rare condition characterized by livedo and multiple ischemic strokes with no apparent cause. This report presents a case of a 34-year-old woman with a 16-year history of livedo who developed right hemibody heaviness, a decrease in visual acuity, and palpitations. The MRI showed bilateral parieto-occipital cortico-subcortical atrophy associated with abnormal signals in the deep white matter, parieto-occipital gliosis foci, and small-caliber artery vasculitis. The patient was eventually diagnosed with Sneddon's syndrome based on her clinical presentation, MRI results, and symptom evolution. The underlying mechanisms of the syndrome remain unclear, but it is thought to involve occlusion of small- and medium-sized arterioles. The neurological involvement of Sneddon's syndrome is highly diverse and dominated by cerebral ischemic events, leading over time to intellectual deterioration or even dementia. This report highlights the importance of considering Sneddon's syndrome as a differential diagnosis in cases of livedo and unexplained cerebral ischemia.

Decrease in Choroidal Vascularity Index of Haller’s layer in diabetic eyes precedes retinopathy

IntroductionThe study aimed to evaluate Choroidal Vascularity Index (CVI) of Haller’s and Sattler’s layers and their relationships with choroidal and retinal thickness, volumes measured on enhanced depth imaging–optical coherence tomography...

The role of skin biopsy in diagnosis and management of calciphylaxis: A retrospective analysis

The role of skin biopsy in diagnosis and management of calciphylaxis: A retrospective analysis

Vascular Microphysiological Systems to Model Diseases.

Human vascular microphysiological systems (MPS) represent promising three-dimensional in vitro models of normal and diseased vascular tissue. These systems build upon advances in tissue engineering, microfluidics, and stem cell differentiation and replicate key functional units of organs and tissues. Vascular models have been developed for the microvasculature as well as medium-size arterioles. Key functions of the vascular system have been reproduced and stem cells offer the potential to model genetic diseases and population variation in genes that may increase individual risk for cardiovascular disease. Such systems can be used to evaluate new therapeutics options.

Cerebral Microvascular and Systemic Effects Following Intravenous Administration of the Perfluorocarbon Emulsion Perftoran.

Oxygen-carrying perfluorocarbon (PFC) fluids have the potential to increase tissue oxygenation during hypoxic states and to reduce ischemic cell death. Regulatory approval of oxygen therapeutics was halted due to concerns over vasoconstrictive side effects. The goal of this study was to assess the potential vasoactive properties of Perftoran by measuring brain pial arteriolar diameters in a healthy rat model. Perftoran, crystalloid (saline) or colloid (Hextend) solutions were administered as four sequential 30 min intravenous (IV) infusions, thus allowing an evaluation of cumulative dose-dependent effects. There were no overall changes in diameters of small-sized (<50 μm) pial arterioles within the Perftoran group, while both saline and Hextend groups exhibited vasoconstriction. Medium-sized arterioles (50–100 μm) showed minor (~8–9%) vasoconstriction within saline and Hextend groups and only ~5% vasoconstriction within the Perftoran group. For small- and medium-sized pial arterioles, the mean percent change in vessel diameters was not different among the groups. Although there was a tendency for arterial blood pressures to increase with Perftoran, pressures were not different from the other two groups. These data show that Perftoran, when administered to healthy anesthetized rats, does not cause additional vasoconstriction in cerebral pial arterioles or increase systemic blood pressure compared with saline or Hextend.

Initial diagnosis of Wegener’s granulomatosis mimicking severe ulcerative colitis: a case report

IntroductionWe describe the case of a woman with an unusual presentation of Wegener’s granulomatosis.Case presentationA 20-year old Caucasian woman presented with the principal feature of a pancolonic, superficial microulceration mimicking severe ulcerative colitis. Our patient was refractory to therapy and had persisting signs of septic shock as well as being at risk of perforation, so we performed a subtotal colectomy and a cholecystectomy due to the incipient necrosis of her gallbladder. Histologic analysis of her colon showed multiple superficial microulcera of the mucosa, lamina propria mucosae and, to a lesser extent, the lamina submucosa. The medium-sized arteries and arterioles of her entire colon, appendix and gallbladder showed acute vasculitic changes with fibrinoid necrosis of the walls and diffuse infiltration with neutrophil granulocytes, accompanied by a strong perivascular histiocyte-rich and partially granulomatous reaction. These findings strongly suggested an autoimmune multisystem disease like Wegener’s granulomatosis or microscopic polyangiitis. A diagnosis of Wegener’s granulomatosis was confirmed by the results of serologic antibody tests: her cytoplasmic antineutrophil cytoplasmic antibody titer was considerably elevated at 1:2560 specific for subclass proteinase 3 (>200kU/L). After the histopathological diagnosis and serological tests, immunosuppression with high doses of corticosteroids and plasmapheresis was started.ConclusionIn critically ill patients with severe, therapy-refractory ulcerative colitis, Wegener´s granulomatosis should be considered and serologic antibody testing should be performed.

Cutaneous polyarteritis nodosa: A rare isolated cutaneous vasculitis

Cutaneous polyarteritis nodosa (CPAN) is a rare form of cutaneous vasculitis that involves small and medium sized arteries of the dermis and subcutaneous tissue without systemic involvement. It presents with tender subcutaneous nodules, digital gangrene, livedo reticularis and subcutaneous ulcerations. The diagnosis is by skin biopsy and characteristic pathologic feature is a leukocytoclastic vasculitis in the small to medium-sized arterioles of the dermis. We report a rare case of benign cutaneous PAN in a 14-year-old girl who presented with history of fever, subcutaneous nodules with cutaneous ulcer and digital gangrene. The skin biopsy showed leukocytoclastic vasculitis with fibrinoid necrosis in the dermal vessels. She received treatment with steroids and lesions resolved completely over a period of month.

The origin of the myofibroblast in fibroproliferative vasculopathy: Does the endothelial cell steer the pathophysiology of systemic sclerosis?

Over the last decade, considerable attention has been paid to the origin of the myofibroblast, the mesenchymal cell type most responsible for the excessive matrix production and deposition in tissue and vessel walls found in fibrotic disorders and fibroproliferative vasculopathies, respectively (1). In this context, the myofibroblast has increasingly been regarded as a crucial effector cell in the pathogenesis of systemic sclerosis (SSc; scleroderma), a multifaceted connective tissue disorder characterized by both skin and internal organ fibrosis and a severe proliferative vasculopathy affecting small and medium-sized arterioles and capillaries (2–4). In SSc, organ dysfunction and failure are ultimately caused by overproduction and accumulation, in affected tissue, of extracellular matrix components, such as types I and III collagen and fibronectin (2,3). Moreover, the concomitant fibroproliferative vasculopathy, characterized by subendothelial intimal fibrosis, may lead to severe vascular complications, including digital ulceration and gangrene, pulmonary arterial hypertension, and scleroderma renal crisis. These events heavily jeopardize patients’ quality of life and are associated with very poor prognosis (4). Despite numerous recent advances in the understanding of the molecular regulation of genes encoding collagens and other extracellular matrix proteins, the complex mechanisms responsible for the heterogeneous pathogenesis of SSc remain unknown (5). As a consequence, no targeted and disease-modifying therapies are available to control, arrest, or reverse disease progression and fibrosis (6). It is well known that fibroblasts are dysregulated, that they transform into myofibroblasts, and that they produce an excessive amount of collagen and other extracellular matrix components in SSc (7). For this reason, the pivotal goal of a research agenda today is the identification of the origin of tissue and subendothelial myofibroblasts, together with the intracellular transduction pathways involved in the transcriptional activation of the genes required for the recruitment and transdifferentiation of myofibroblasts from their putative cellular precursors.

Vascular Gene Transfer of SDF-1 Promotes Endothelial Progenitor Cell Engraftment and Enhances Angiogenesis in Ischemic Muscle

Gene therapy approaches to enhance endothelial progenitor cell (EPC) homing may augment cell engraftment to ischemic tissue and lead to a greater therapeutic response. Therefore, we assessed the effects of ultrasound-mediated (UM) transfection of the chemokine stromal cell-derived factor-1 (SDF-1) on homing and engraftment of intravenously administered EPCs and the subsequent angiogenic response in chronically ischemic skeletal muscle. Bone marrow-derived EPCs were isolated from donor Fisher 344 rats, cultured and labeled in preparation for injection into recipient animals via a jugular vein. Using a model of chronic hindlimb ischemia in rats, we demonstrated that UM destruction of intravenous carrier microbubbles loaded with SDF-1 plasmid DNA resulted in targeted transfection of the vascular endothelium within ischemic muscle and greater local engraftment of EPCs. The combination of SDF-1gene therapy and EPCs lead to the greatest increase in tissue perfusion and microvascular density within ischemic muscle, compared to no treatment or either monotherapy alone. Our results demonstrate that UM transfection of SDF-1 improves EPC targeting to chronically ischemic tissue, enhancing vascular engraftment and leading to a more robust neovascularization response.

Effectiveness of Radiotherapy in Myxoid Sarcomas Is Associated With a Dense Vascular Pattern

Surgery and adjuvant radiotherapy (RT) have long been the standard treatment for most deep-seated sarcomas; however, since the randomized trial from the National Cancer Institute of Canada, which described similar local control for pre- vs. postoperative RT, both modalities are now widely accepted. As a group, sarcomas are classified as radiation resistant. The subgroup of myxoid liposarcoma (MLS), a sarcoma with a typical vascular crow's feet pattern, is highly radiosensitive, but a mechanism for this phenomenon is unknown. Here we describe our results with preoperative RT and propose a mechanism explaining the high sensitivity based on the distinctive vascularization pattern of MLS. Between 2002 and 2006, 31 sarcoma patients, including 10 with MLS, underwent preoperative RT at our institute. Resected specimens were histologically evaluated, focusing on classification, grade, and vascularization patterns. Twenty sarcomas showed more than 80% pathologic response after preoperative RT. A pathologic complete response was found in all "pure" MLS specimens after preoperative RT (n = 8). There were no pathologic complete responses in the remaining sarcoma patients (n = 23), although 12 showed 80% to 90% pathologic response. In contrast to the remaining RT-resistant sarcomas, the highly responding specimens contained branching vasculature, partial thrombus formation and inflammation of medium sized arterioles, similar to the vascular changes in MLS. Both MLS and sarcomas with MLS-like vasculature are highly radiosensitive. Radiation sensitivity may be explained by changes in medium-sized arterioles, obstructing the specific crow's feet vascularization and inducing hypoxia with secondary tumor cell death.

What Causes Nephrogenic Systemic Fibrosis?

What Causes Nephrogenic Systemic Fibrosis?

Intravital microscopy of the murine pulmonary microcirculation

Intravital microscopy (IVM) is considered as the gold standard for in vivo investigations of dynamic microvascular regulation. The availability of transgenic and knockout animals has propelled the development of murine IVM models for various organs, but technical approaches to the pulmonary microcirculation are still scarce. In anesthetized and ventilated BALB/c mice, we established a microscopic access to the surface of the right upper lung lobe by surgical excision of a window of 7- to 10-mm diameter from the right thoracic wall. The window was covered by a transparent polyvinylidene membrane and sealed with alpha-cyanoacrylate. Removal of intrathoracic air via a trans-diaphragmal intrapleural catheter coupled the lung surface to the window membrane. IVM preparations were hemodynamically stable for at least 120 min, with mean arterial blood pressure above 70 mmHg, and mean arterial Po(2) and arterial Pco(2) in the range of 90-100 Torr and 30-40 Torr, respectively. Imaged lungs did not show any signs of acute lung injury or edema. Following infusion of FITC dextran, subpleural pulmonary arterioles and venules of up to 50-microm diameter and alveolar capillary networks could be visualized during successive expiratory plateau phases over a period of at least 2 h. Vasoconstrictive responses to hypoxia (11% O(2)) or infusion of the thromboxane analog U-46619 were prominent in medium-sized arterioles (30- to 50-microm diameter), minor in small arterioles <30 microm, and absent in venules. The presented IVM model may constitute a powerful new tool for investigations of pulmonary microvascular responses in mice.

Images in vascular medicine

A 61-year-old Caucasian female with prior history of bilateral femoro-popliteal bypass grafts, chronic venous insufficiency and long-standing rheumatoid arthritis was admitted with painful bilateral lower extremity ulcerations. Presumptive diagnosis of infected venous or vasculitic ulcers was made and vascular medicine consultation was obtained. Anterolateral aspects of bilateral lower extremities were erythematous and revealed several tender ulcers with well-defined edges. The ulcer bases were composed of predominantly pale granulation tissue and serous discharge (Panel A). Ankle‐brachial index and toe pressures were normal at rest. Pertinent laboratory results included a rheumatoid factor of 392 IU/ml and a Westergren sedimentation rate of 115 mm/h. The serum cryoglobulins, C-ANCA, PANCA and complement levels (C3/C4) were within normal limits. An MRI did not suggest osteomyelitis. A wound biopsy was requested due to the atypical nature of the ulcers and revealed cutaneous large T-cell lymphoma. Panel B shows the microscopic appearance of the large T-cell lymphoma with angioinvasive features. Beneath an ulcerated epidermis, malignant lymphoid cells infiltrate the deep dermis and subcutis and invade small and medium-sized arterioles in the deep dermis (1: hematoxylin and eosin, 200). At higher magnification, the cells have a large cell morphology (2: hematoxylin and eosin, 400). Immunohistochemistry for the T-cell-associated antigen CD3 shows a brown colorimetric reaction decorating the cytoplasmic membranes of the neoplastic cells (3: anti-CD3, 400). CHOP chemotherapy was started but she died several months after the diagnosis. Malignant transformation of chronic ulcers is well documented, although uncommon. 1 Patients with rheumatoid arthritis frequently present with leg ulceration 2 and are at increased risk for lymphoma. 3

A Case Report Comparing Various Radiological Tests in the Diagnosis of Calcific Uremic Arteriolopathy

Calcific uremic arteriolopathy (CUA) is a rare necrotizing skin condition characterized by calcification in arterioles, leading to ischemia and skin ulcerations. This disease affects 1% to 4% of patients with chronic kidney disease and has a reported mortality rate up to 80%. The diagnosis of CUA is based on clinical judgment suggested by the characteristic skin lesions. Although skin biopsy is the gold standard for establishing the diagnosis, it is performed infrequently because of poor healing and risk for secondary infections. In this case report, we compare the ability of various radiological tests to show arteriolar calcifications of patients with CUA. Our patient had biopsy-proven CUA manifesting as chronic nonhealing ulcers of the calves. She underwent soft-tissue x-ray of the affected extremities and high-resolution (0.5-mm slice) computed tomographic (CT) scanning with 3-dimensional image reconstruction. We also used a dedicated mammography machine to obtain images of the patient's calves. Images were compared based on the ability to show small-vessel calcification. Plain soft-tissue x-ray showed mildly increased soft-tissue density and very few calcified vessels, whereas CT showed few calcified small- and medium-sized arterioles. Diffuse calcification of small arterioles in a mesh-like pattern was shown by means of the mammography technique. Simple, safe, and inexpensive x-ray imaging using the mammography technique was superior to plain soft-tissue x-ray and 3-dimensional CT in showing the hallmark arteriolar calcifications of patients with CUA. Thus, we propose a possible role for this technique in diagnosing CUA.

La biopsie neuro-musculaire dans le diagnostic des vascularites

One characteristic histological lesion on biopsy specimens is mandatory to establish the diagnosis of vasculitis. Combined nerve and muscle biopsies, by the same cutaneous incision, improve significantly the percentage of positive results. Nerve fragments should be taken in every patient presenting sensory manifestations. Such vasculitic lesions are present in medium-sized arterioles and/or small vessels, and correspond mainly to 4 necrotizing vasculitis: panarteritis nodosa (PAN), microscopic polyangiitis (MPA), Churg and Strauss syndrome and Wegener granulomatosis. Microvasculitis should be added to these classical entities, because it corresponds to small vessel wall infiltration by inflammatory cells, as observed in PAN and MPA, but without any necrosis. Microvasculitis has to be differentiated from the inflammatory cell infiltrates surrounding small vessels. However, such perivascular inflammatory cell infiltrates enable the diagnosis of probable vasculitis when associated with clusters of neo-vessels, hemosiderin deposits, or a focal damage of nerve fibers. Grossly, one third of vasculitis diagnosis is confirmed on muscle fragments, a second third on nerve fragments, and the last third on both nerve and muscle fragments. Moreover, in the search for vasculitis, an unpredicted diagnosis of lymphoma or amyloidosis is occasionally established on the neuro-muscular biopsy.

Cocaine-induced midline destructive lesions: clinical, radiographic, histopathologic, and serologic features and their differentiation from Wegener granulomatosis.

Cocaine-induced midline destructive lesions: clinical, radiographic, histopathologic, and serologic features and their differentiation from Wegener granulomatosis.

Transmyocardial channeling

Transmyocardial channeling

The nerve distribution in the testis of the cat

The autonomous innervation of the feline testis was investigated by immunohistochemistry and a modified acetylcholinesterase technique. The nerves reach the testis mainly by two routes: (1) with testicular artery and pampiniform plexus to the cranial extremity (funicular contribution), (2) from the epididymal tail to the caudal extremity (caudal contribution). Within the tunica albuginea the funicular contribution supplies the cranial two thirds, whereas the caudal third of the tunica receives its nerves via the ligamentous connection between testis and epididymal tail. The nerve bundles accompanying the testicular artery give branches to the arterial wall and the pampiniform plexus. When reaching the cranial testicular pole the bundles separate; the majority of them pass into the centrally located mediastinum testis, another large portion enters the tunica albuginea, particularly on its epididymal side. The septula testis are innervated from both sides, that is from the mediastinum and from the tunica albuginea. In the cat, contrary to other mammals, all septula are innervated. Furthermore, nerve fibers occur regularly within the testicular lobules. Generally, the testicular nerves of the cat are unmyelinated and mainly vascular nerves, but fibers are also found within the connective tissue compartments of the testis. The vast majority of all autonomous testicular nerves are postjunctional sympathetic fibers. Terminal ramifications of cholinergic fibers are exclusively observed in the wall of medium-sized arterioles within mediastinum, septula and lobuli testis. Neuropeptide Y is the most frequent peptidergic transmitter in feline testicular vascular plexuses. The amount of calcitonin gene-related peptide-positive fibers is also remarkably high in the testis, but prefers a location within the stroma of the tunica albuginea, mediastinum and septula. In the cat, Leydig cells occur not only in intertubular locations, but also as intratunical and mediastinal Leydig cells. In all three localizations solitary nerve fibers are observed between Leydig cell groups. These fibers are generally dopamin-beta-hydroxylase- and tyrosine hydroxylase-positive, some contain calcitonin gene-related peptide and, very few, substance P.

Pulmonary Microvascular Changes during Sepsis: Evaluation Using Intravital Videomicroscopy

A variety of pulmonary microvascular changes occur during sepsis. These include abnormal vascular reactivity, leukocyte sequestration, and leakage of protein into the alveoli. Based on intravital videomicroscopy we have developed a method to directly assess in vivo the changes that occur in the pulmonary microcirculation in a rat model of sepsis. Male Sprague–Dawley rats were assigned to control or sepsis groups. Sepsis was induced by cecal ligation and perforation. Twenty four hours later, rats were anesthetized, mechanically ventilated, and their lung prepared for intravital videomicroscopy. A specially designed transparent thoracic window was inserted into the chest wall. The dependent surface of the lung was superfused with saline solution and visualized with an inverted microscope. Vascular contractility, to phenylephrine, (PE) and hypoxia of small (15–25 μm in diameter) and medium (40–50 μm) arterioles was examined. Leukocyte traffic in the pulmonary microcirculation was studied after in vivo labeling of leukocytes with Rhodamine and visualized with fluorescence microscopy. Leak of albumin into the alveolar space was measured with FITC-labeled albumin and fluorescence microscopy. Both small and medium sized pulmonary arterioles in septic animals exhibited attenuated vascular contractility to phenylephrine, but only medium-sized arterioles displayed hypocontractility to hypoxia. Further, in septic animals there was an increase in both the number of stationary leukocytes in the pulmonary microcirculation and an increase in alveolar capillary protein leak. We conclude: (1) direct visualization of the pulmonary microvascular pressor response to hypoxia and PE in the rat is possible using this technique, (2) similar to previous in vitro studies with larger vessels, pulmonary arterioles have an attenuated contractile response to PE and hypoxia in sepsis, and (3) there is an increase in both the number of stationary leukocytes and protein leak into the alveolus in the lungs of septic animals.