Vascular Obliteration Research Articles

Endothelial to mesenchymal transition: a precursor to post-COVID-19 interstitial pulmonary fibrosis and vascular obliteration?

Endothelial to mesenchymal transition (EndMT) could lead to post-COVID-19 pulmonary fibrosis and vascular remodelling https://bit.ly/2QqSKxT

Rank Order of Small Molecule Induced Hypoxiamimesis to Prevent Retinopathy of Prematurity.

Here we rank order small molecule inhibitors of hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) using severity of oxygen induced retinopathy (OIR) as an outcome measure. Dose response analyses in cell cultures of hepatoma (Hep3B), retinal Müller cells (MIO-M1) and primary retinal endothelial cells were conducted to evaluate potency by comparing dose to HIF-1,2 protein levels by western blotting. In vivo dose response was determined using the luciferase-transgene HIF reporter (luc-ODD). Each compound was placed in rank order by their ability to reduce neovascularization and capillary drop out in the OIR mouse model. An Epas1 KO confined to retinal Müller cells was used to determine whether successful protection by HIF stabilization requires HIF-2. Two candidate small molecules can prevent OIR by stabilizing HIF-1 to prevent oxygen induced growth attenuation and vascular obliteration. Müller cell HIF-2, the mediator of pathologic retinal angiogenesis, is not required for protection. The lack of dependence on Müller cell HIF-2 predicts that inhibition of HIF PHD will not drive pathological angiogenesis.

Advanced Diagnosis and Therapy for Pulmonary Arterial Hypertension

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and progressive disease, which often leads to premature death. Pulmonary arterial hypertension (PAH, group 1 PH) comprises of diverse diseases that result in similar pathological changes, including the medium-sized pulmonary arteries and pulmonary arterioles characterized by vascular obliteration. The evaluation and diagnosis of PH and PAH were re-defined based on proceedings of the 6th World Symposia on Pulmonary Hypertension (WSPH). Accurate early diagnosis and subsequent therapy of PAH are necessary, as management of this disease is still challenging, and life expectancy is remaining suboptimal. This review task force reflects the multidisciplinary nature of PAH, including the definition, epidemiology, genetics, especially the advanced diagnosis and the therapy development in recent years.

ODONTOLOGICAL EFFECTS OF IONIZING RADIATION (review).

Odontological effects of ionizing radiation (IR) as a result of radiotherapy, the consequences of accidents at nuclear power plants and industry, individual occupational exposure, etc. deserve significant attention interns of radiation medicine and radiation safety. to analyze and summarize clinical and experimental data on the odontological radiation effects. the pathological changes in the hard tissues of teeth, pulp, periodontium, mucousmembranes of the mouth and jaws due to exposure to IR. search in the PubMed / MEDLINE, Google Scholarabstract medical and biological databases, scientific libraries of the relevant sources of scientific information. Radiobiological effects of IR due to its direct and indirect action are manifested throughout the period ofodontogenesis and formation of the facial skeleton. Experimental and clinical data (in children and adults) indicatethe increased risk of dental caries, reduction of pain threshold and vascularization of tooth pulp along with its fibrosis and atrophy, periodontal dysfunction, which predispose to a high probability of tooth loss. Abnormalities in theactivity of osteoblasts and cementoblasts of dental periosteum and osteoblasts of alveolar process in combinationwith circulatory disorders due to endothelial cell death, hyalinization, thrombosis and vascular obliteration increasethe risk of jaw osteoradionecrosis. Children who have undergone a prenatal exposure to IR as a result of theChornobyl NPP accident have a premature change of teeth. Deterioration of periodontal tissues and early development of acute and complicated dental caries are typical for children and adults affected by the Chornobyl disaster. Summarized data on the effects of radiation exposure under different conditions on teeth primordia(i.e. immature teeth), their formation and eruption in experimental and clinical settings, as well as on the odontological radiation effects in adults are summarized. Condition of the teeth in the Chornobyl NPP accident survivorsis described. Understanding and taking into account the radiobiological odontological effects is necessary in thelight of planning, preparing, and conducting local radiation therapy and developing the standards of radiation safety and measures to protect professionals and the public in the event of possible radiation accidents at the nuclearpower plants and industry facilities.

Predicting Visual Acuity Deterioration and Radiation-Induced Toxicities after Brachytherapy for Choroidal Melanomas.

Ruthenium-106 (Ru-106) brachytherapy is an established modality for eye-preserving treatment of choroidal melanoma. To achieve optimal treatment outcomes, there should be a balance between tumour control and the risk of healthy tissue toxicity. In this retrospective study, we examined normal tissue complication probability (NTCP) for visual acuity deterioration and late complications to aid the understanding of dose-dependence after Ru-106 treatments. We considered consecutive patients diagnosed with choroidal melanoma and primarily treated at a single institution from 2005–2014. Treatment plans were retrospectively recreated using dedicated software and image guidance to contour the tumour and determine the actual plaque position. Dose distributions were extracted from each plan for all relevant anatomical structures. We considered visual acuity deterioration and late complications (maculopathy, optic neuropathy, ocular hypertension, vascular obliteration, cataract and retinal detachment). Lasso statistics were used to select the most important variables for each analysis. Outcomes were related to dose and clinical characteristics using multivariate Cox regressions analysis. In total, 227 patients were considered and 226 of those were eligible for analysis. Median potential follow-up time was 5.0 years (95% CI: 4.5–6.0). Visual acuity deterioration was related to optic disc-tumour distance and dose metrics from the retina and the macula, with retina V10Gy showing the strongest correlation. Macula V10Gy was the only dose metric impacting risk of maculopathy, while optic disc-tumour distance also proved important. Optic disc V50Gy had the largest impact on optic neuropathy along with optic disc-tumour distance. Optic disc V20Gy was the only variable associated with vascular obliteration. Lens D2% had the largest impact on the risk of cataract along with older age and the largest base dimension. We found no variables associated with the risk of ocular hypertension and retinal detachment. Visual acuity deterioration and most late complications demonstrated dependence on dose delivered to healthy structures in the eye after Ru-106 brachytherapy for choroidal melanomas.

PB2068 THE CASTLEMAN DISEASE: HISTOLOGICAL VARIANTS, POEMS‐SYNDROME AND PRODUCTIVE PLASMA CELL VASCULITIS

Background:The Castleman disease (CD) is a rare, little‐studied disease characterized by lymphadenopathy with follicles hyperplasia and active neoangiogenesis. Occurs in the form of two histological variants: plasma cell and hyaline‐vascular. The total vasculitis in the vessels of internal organs, previously not noted by researchers, was revealed in the analysis of 2 sectional cases of CD.Aims:To study the state of microcirculatory vessels in patients with plasma cell and hyaline‐vascular type of CD in sections of biopsied lymph nodes.MethodsSections of biopsied lymph nodes were used. It was used hematoxylin‐eosin and reaction to antibodies to CD138 to identify plasma cells. In all patients with plasma cell variant cells were painted with antibodies to HSV‐8. Vessels estimated in perinodular tissue of capsule and fat. We examined 15 patients with CD. According to histology and CD138 content, the plasma cell variant was diagnosed in 8 patients, 7 men and 1 woman aged from 40 to 70 years. In 5 patients approved POEMS syndrome by the presence of M‐protein, disorders of neuro‐muscular conduction according to the electro‐neuromyography, and other symptoms. In 7 patients was diagnosed hyaline vascular type of CD, including 5 women and 2 men aged from 30 to 60 years.Results:In 1 patient with plasma cell variant of CD revealed HSV8 reaction with intranuclear staining antibodies. Vasculitis in the form of vascular walls thickening of the microcirculatory bloodstream with a decrease or obliteration of their lumen, wall fibrosis and plasma cell infiltration was found in all 15 patients. The most pronounced changes in the form of fibrosis, complete vascular obliteration and massive perivascular infiltration CD138+ cells by type of massive colonies of hundreds of cells were found in patients with the POEMS‐ syndrome. They also noted the location of single CD138 + cells inside the intima of the sclerosal vessels. Fibroplastic vascular changes in patients with POEMS‐syndrome were weirdly shaped in the form of “mood masks”. It coincided with massive osteosclerotic changes of the vertebrae on radiographs. Massive development of fibrosis corresponds to the POEMS pathogenesis. All patients with its presence later died.Summary/Conclusion:The Castleman disease, regardless of the histological variant, includes in its morphological pattern productive plasma cell vasculitis, most pronounced in the plasma‐cell variant with POEMS‐ syndrome.

Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a debilitating disease associated with progressive vascular remodeling of distal pulmonary arteries leading to elevation of pulmonary artery pressure, right ventricular hypertrophy, and death. Although presenting high levels of DNA damage that normally jeopardize their viability, pulmonary artery smooth muscle cells (PASMCs) from patients with PAH exhibit a cancer-like proproliferative and apoptosis-resistant phenotype accounting for vascular lumen obliteration. In cancer cells, overexpression of the serine/threonine-protein kinase CHK1 (checkpoint kinase 1) is exploited to counteract the excess of DNA damage insults they are exposed to. This study aimed to determine whether PAH-PASMCs have developed an orchestrated response mediated by CHK1 to overcome DNA damage, allowing cell survival and proliferation. Approach and Results: We demonstrated that CHK1 expression is markedly increased in isolated PASMCs and distal PAs from patients with PAH compared with controls, as well as in multiple complementary animal models recapitulating the disease, including monocrotaline rats and the simian immunodeficiency virus-infected macaques. Using a pharmacological and molecular loss of function approach, we showed that CHK1 promotes PAH-PASMCs proliferation and resistance to apoptosis. In addition, we found that inhibition of CHK1 induces downregulation of the DNA repair protein RAD 51 and severe DNA damage. In vivo, we provided evidence that pharmacological inhibition of CHK1 significantly reduces vascular remodeling and improves hemodynamic parameters in 2 experimental rat models of PAH. Our results show that CHK1 exerts a proproliferative function in PAH-PASMCs by mitigating DNA damage and suggest that CHK1 inhibition may, therefore, represent an attractive therapeutic option for patients with PAH.

Immunoglobulin G4-related lung disease in an adolescent patient

Immunoglobulin G4-related disease is a recently recognized systemic immune-mediated condition characterized by lymphoplasmacytic infiltrate in various organs with IgG4 positive plasma cells. Isolated lung involvement is rare, difficult to diagnose and can mimic primary lung malignancy on imaging. We report the case of an isolated IgG4-related interstitial lung disease in a 16-year-old asymptomatic male adolescent with incidentally found bilateral nodular lesions by chest radiograph. The patient underwent surgical interventions for assumption of malignancy. Serum IgG4 levels was normal. Н istological examination revealed significant lymphoplasmacytic infiltrate with lymphoid follicle formation, peribronchial fibrosis, vascular obliteration. Prominent interstitial IgG4 positive plasma cell infiltrate was identified by immunohistochemistry. Isolated IgG4-related lung disease should be taken into account as a possible differential diagnosis of mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis.

Recent development of balloon-occluded retrograde transvenous obliteration.

Gastric varices (GVs) are a major complication of portal hypertension in patients with liver cirrhosis. The mortality rate associated with the bleeding from GVs is not low. Balloon-occluded retrograde transvenous obliteration (BRTO) was first introduced by Kanagawa et al. as a treatment for isolated GVs in 1994. It has been performed most frequently in Asia, especially in Japan. Ethanolamine oleate was the original sclerosant used in the therapy. Since the late 2000s, BRTO using sodium tetradecyl sulfate foam or polidocanol foam as a sclerosant has been performed in many countries other than Japan. Then, early in the 2010s, modified BRTO techniques including vascular plug-assisted retrograde transvenous obliteration and coil-assisted retrograde transvenous obliteration were developed as an alternative treatment for GVs. This article provides a historical overview of BRTO using various sclerosants and modified BRTO techniques, such as plug-assisted retrograde transvenous obliteration and coil-assisted retrograde transvenous obliteration.

The soluble epoxide hydrolase attenuates pathological vascularization by preventing astrocyte loss in a retinopathy of prematurity model in mice

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Several signalling pathways have been implicated in the process of ROP but a novel drugable target is the cytochrome P450 (CYP)/soluble epoxide hydrolase (sEH) pathway. The latter enzymes play a crucial role in biological processes by generating bioactive epoxides and diols from endogenous polyunsaturated fatty acids (PUFAs). This study aimed to characterize the effects of the newly identified sEH‐derived w‐3 PUFA diol; 19,20‐dihydroxydocosapentaenoic acid (DHDP) in a mouse ROP model.ROP in mice was achieved by placing pups in 75% oxygen for 5 days from postnatal day (P) 7 until P12, before moving animals back to room air for an additional 5 days. This procedure resulted in the development of avascular areas that were significantly larger in retinas from sEH−/− mice than in their wild‐type (WT) littermates at P17. Avascularization was accompanied by angiogenesis in the form of characteristic vascular “tufts” which were more evident in retinas from sEH−/− mice. Although there was no difference in vascular obliteration, a marked decrease in the astrocyte network was observed in sEH−/− mice after exposure to high oxygen. Mechanistically, astrocyte loss in hyperoxic conditions was a consequence of elevated mitochondrial (mt) DNA damage mediated by increased interaction of the PARP‐1 DNA binding domain with mtDNA, as revealed by chromatin immunoprecipitation studies. Exposure of astrocytes to 75% O2 in vitro resulted in elevated PARP‐1 cleavage/activation; a phenomenon reversed in the presence of 19,20‐DHDP. Administration of 19,20‐DHDP during hyperoxia preserved the complex of presenilin 1 with mitochondrial carrier homolog 1 (MTCH‐1) in the outer mitochondria membrane, inhibiting the translocation of the MTCH‐1 to the inner mitochondria membrane and subsequently inhibiting PARP‐1 cleavage. The intravitreal injection of 19,20‐DHDP at day 7 significantly prevented astrocyte loss caused by high O2 levels at day 8, and reduced both the avascular area as well as vascular tuft formation at P17 in the sEH−/− mice.Our date indicate that the sEH dependent generation of 19,20‐DHDP from w‐3PUFA is required for retinal astrocyte survival and preservation of DNA integrity under hyperoxic conditions.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Modified Balloon-Occluded Retrograde Transvenous Obliteration (BRTO) Techniques for the Treatment of Gastric Varices: Vascular Plug-Assisted Retrograde Transvenous Obliteration (PARTO)/Coil-Assisted Retrograde Transvenous Obliteration (CARTO)/Balloon-Occluded Antegrade Transvenous Obliteration (BATO).

Gastric varices in the setting of portal hypertension occur less frequently than esophageal varices but occur at lower portal pressures and are associated with more massive bleeding events and higher mortality rate. Balloon-occluded retrograde transvenous obliteration (BRTO) of gastric varices has been well documented as an effective therapy for portal hypertensive gastric varices. However, BRTO requires lengthy, higher-level post-procedural monitoring and can have complications related to balloon rupture and adverse effects of sclerosing agents. Several modified BRTO techniques have been developed including vascular plug-assisted retrograde transvenous obliteration, coil-assisted retrograde transvenous obliteration, and balloon-occluded antegrade transvenous obliteration. This article provides an overview of various modified BRTO techniques.

Scleroderma in Guinea’s African: Epidemiological, Clinical and Therapeutic Aspects

Introduction: Scleroderma is a generalized condition of the connective tissue, arterioles and micro-vessels characterized by tissue fibrosis, vascular obliteration and abnormal humoral and cellular immune responses. The aim of this study was to describe the epidemiological, clinical, therapeutic and evolutionary aspects of scleroderma at the Department of Dermatology-Venerology at Donka National Hospital. Methods: This was a descriptive cross-sectional study with a retrospective collection of data for a period of 11 years, from January 1, 2000, to December 31, 2010, covering all inpatient records of Scleroderma in the service. Results: We collected 17 cases of scleroderma out of 3289, a frequency of 0.04%. The average age of patients was 33.33 years with extremes of 10 and 60 years. A female predominance was noted with a sex ratio M/F of 0.13. Cutaneous induration was the main symptom associated with the phenomenon of Raynaud, and disorders of pigmentation. The extra-skin manifestations were mainly dominated by gastrointestinal involvement (32%), pulmonary involvement (24%), cardiac (20%), articular (20%) and renal (12%) involvement. The systemic form was the most common (99.45%). Corticotherapy was the most prescribed treatment (24.59%). Clinical improvement was noted in (93.2%) of the cases. Conclusion: Scleroderma, although rare, deserves special attention at all levels for early diagnosis.

Fetal Vascular Malperfusion.

- Fetal vascular malperfusion, also known as fetal thrombotic vasculopathy, remains an underrecognized pathologic finding and should be noted during placental evaluation. - To review histologic findings, gain familiarity with the updated terminology, and to recognize important clinical associations with this entity. - University of Michigan cases, PubMed search, multiple review articles including recent placental workshop group consensus statement, and selected book chapters. - Multiple histologic patterns of fetal vascular malperfusion have been described including thrombosis, avascular villi, villous stromal-vascular karyorrhexis, intramural fibrin thrombi, and stem villous vascular obliteration. Various underlying etiologies can be involved in fetal vascular malperfusion. Cord lesions including abnormal insertion, length, and coiling are important causes. Maternal vascular malperfusion such as preeclampsia, hypercoagulable states, lupus anticoagulant, and sometimes diabetes have been associated with this condition. Fetal cardiac dysfunction/malformations and severe fetal inflammatory response in the setting of ascending intrauterine infection have also been attributed to this important finding. Fetal vascular malperfusion has been implicated in several significant and sometimes devastating clinical associations; these include intrauterine growth restriction, poor perinatal outcome, fetal demise, and neurodevelopmental sequelae. A diagnostic challenge may be encountered in cases with prior intrauterine fetal death, since degenerative changes post demise result in a similar histomorphologic picture. The diffuse versus the focal nature of the lesions may help in the distinction.

Masson's tumor revealed by an intracerebral hematoma. Case report and a review of the literature

We report the case of a 56-year-old woman who underwent total resection of a Masson's tumor or intravascular papillary endothelial hyperplasia (IPEH), which was discovered due to a left temporal intracerebral hematoma revealed by aphasia. IPEH is more often localized on cutaneous and subcutaneous locations, intracranial IPEH are rare and only approximately twenty cases have been published to date. These tumors are a benign vascular lesion composed of papillary intravascular proliferation of epithelial cellular associated thrombosis with fibrin deposits responsible for vascular lumen obliteration. Differential diagnoses of neurological locations of IPEH are more often an angiosarcoma, or meningioma, and metastasis. Magnetic Resonance imaging (MRI) and CT-scan are not specific. On CT-scan the lesion is hypodense without calcification with a peripheral enhancement and on MRI a hyposignal T1 with homogeneous enhancement and a hypersignal T2. Arteriography may reveal a tumoral blush and arterio-venous shunt or arterial pedicles which can be embolized. The age of discovery is between 12 and 70 with a female predominance. IPEH are often localized close to the venous sinus or can be developed in a vascular malformation, thrombus or aneurysm. The curative treatment is total resection but recurrence has been reported, long-term follow-up with MRI is recommended.

Pulmonary hypertension in sarcoidosis

Pulmonary hypertension (PH) is a relatively common complication of sarcoidosis. In different studies, prevalence of PH in sarcoidosis varies from 6% to 74%. PH associated with sarcoidosis (PHAS) is typically associated with poor prognosis. Though PHAS is diagnosed more often in patients with advanced sarcoidosis, it could occasionally occur without pulmonary parenchymal lesions. Pathophysiology of PHAS is quite complex and includes several mechanisms including pulmonary fibrosis, hypoxic vasoconstriction, pulmonary vascular granulomatous obliteration and / or angiitis, extrinsic pulmonary vascular compression, pulmonary venoocclusive disease, and left heart disease. Management of PHAS is based on treatment of hypoxemia, active sarcoidosis and comorbidities. A role of systemic steroids in therapy of PHAS remains controversial. Pulmonary arterial hypertension (PAH) specific therapy has not been yet recommended in PHAS, but prostanoids, endothelin receptor antagonists and phosphodi esterase5 inhibitors were effective in some patients with PHAS in several small trials. Additional welldesigned randomized placebocontrolled studies are needed to investigate a role of PAHspecific therapy in certain cohorts of patients with PHAS.

Lutein facilitates physiological revascularization in a mouse model of retinopathy of prematurity.

Retinopathy of prematurity is one of the leading causes of childhood blindness worldwide, with vessel growth cessation and vessel loss in phase I followed by neovascularization in phase II. Ischaemia contributes to its pathogenesis, and lutein protects against ischaemia-induced retinal damages. We aimed to investigate the effects of lutein on a murine model of oxygen-induced retinopathy. Mouse pups were exposed to 75% oxygen for 5days and returned to room air for another 5days. Vascular obliteration, neovascularization and blood vessel leakage were examined. Immunohistochemistry for glial cells and microglia were performed. Compared with vehicle controls, mouse pups receiving lutein treatment displayed smaller central vaso-obliterated area and reduced blood vessel leakage. No significant difference in neovascular area was found between lutein and vehicle controls. Lutein promoted endothelial tip cell formation and maintained the astrocytic template in the avascular area in oxygen-induced retinopathy. No significant changes in Müller cell gliosis and microglial activation in the central avascular area were found in lutein-treated pups. Our observations indicated that lutein significantly promoted normal retinal vascular regrowth in the central avascular area, possibly through promoting endothelial tip cell formation and preserving astrocytic template. Our results indicated that lutein might be considered as a supplement for the treatment of proliferative retinopathy of prematurity because of its role in facilitating the revascularization of normal vasculature.

Absence of macrophage migration inhibitory factor reduces proliferative retinopathy in a mouse model.

Ischemia-induced neovascularization is the key feature of proliferative diabetic retinopathy. Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory and proangiogenic cytokine, and its levels are elevated in the vitreous of patients with proliferative diabetic retinopathy. In this study, we aimed at investigating the relative potential of MIF in the ischemia-induced retinal neovascularization. Both WT and MIF-knockout mice were subjected to the retinopathy of prematurity (ROP) model. Intraretinal vessel regrowth was assessed by whole-mount immunofluorescence, and preretinal neovascularization was analyzed in retinal vertical sections after periodic acid-Schiff staining in the hypoxic stage of the ROP model. Gene expression of selected proangiogenic and proinflammatory factors at postnatal day 13 (p13) was measured by real-time PCR. Vascular endothelial growth factor (VEGF) expression, recruitment of endothelial progenitor cells (EPCs) and microglial activation were analyzed with immunofluorescence. MIF deficiency increased areas of vascular obliteration by 49%, reduced sprouting tips by 27% and inhibited preretinal angiogenesis by 35%. VEGF expression was reduced in Müller cells of MIF-knockout mice. MIF absence reduced gene expression of erythropoietin, tumor necrosis factor alpha and intercellular adhesion molecule-1 by 30, 70 and 50%, respectively, decreased the number of retinal EPCs by 37.5% and inhibited microglial activation in the hypoxic condition. In conclusion, we found that MIF has proangiogenic and proinflammatory properties in retinal neovascularization. The proangiogenic role of MIF in ischemia-induced retinal neovascularization is associated with the expression of VEGF and erythropoietin, EPC recruitment and inflammation. Therefore, MIF has a potential role in the pathological angiogenesis of proliferative retinopathy.

The right ventricle: interaction with the pulmonary circulation.

The primary role of the right ventricle (RV) is to deliver all the blood it receives per beat into the pulmonary circulation without causing right atrial pressure to rise. To the extent that it also does not impede left ventricular (LV) filling, cardiac output responsiveness to increased metabolic demand is optimized. Since cardiac output is a function of metabolic demand of the body, during stress and exercise states the flow to the RV can vary widely. Also, instantaneous venous return varies widely for a constant cardiac output as ventilatory efforts alter the dynamic pressure gradient for venous return. Normally, blood flow varies with minimal changes in pulmonary arterial pressure. Similarly, RV filling normally occurs with minimal increases in right atrial pressure. When pulmonary vascular reserve is compromised RV ejection may also be compromised, increasing right atrial pressure and limiting maximal cardiac output. Acute increases in RV outflow resistance, as may occur with acute pulmonary embolism, will cause acute RV dilation and, by ventricular interdependence, markedly decreased LV diastolic compliance, rapidly spiraling to acute cardiogenic shock and death. Treatments include reversing the causes of pulmonary hypertension and sustaining mean arterial pressure higher than pulmonary artery pressure to maximal RV coronary blood flow. Chronic pulmonary hypertension induces progressive RV hypertrophy to match RV contractility to the increased pulmonary arterial elastance. Once fully developed, RV hypertrophy is associated with a sustained increase in right atrial pressure, impaired LV filling, and decreased exercise tolerance. Treatment focuses on pharmacologic therapies to selectively reduce pulmonary vasomotor tone and diuretics to minimize excessive RV dilation. Owning to the irreversible nature of most forms of pulmonary hypertension, when the pulmonary arterial elastance greatly exceeds the adaptive increase in RV systolic elastance, due to RV dilation, progressive pulmonary vascular obliteration, or both, end stage cor pulmonale ensues. If associated with cardiogenic shock, it can effectively be treated only by artificial ventricular support or lung transplantation. Knowing how the RV adapts to these stresses, its sign posts, and treatment options will greatly improve the bedside clinician’s ability to diagnose and treat RV dysfunction.

Vascular Plug-Assisted Retrograde Transvenous Obliteration for the Management of Gastric Varices: Comparative Effectiveness between Gelatin Sponge Embolization and Permanent Sclerosant

Upper gastrointestinal endoscopy is usually the first-line diagnostic and management tool for bleeding gastric varices (1). When endoscopy fails to control gastric variceal bleeding, a transjugular intrahepatic portosystemic shunt (TIPS) is recommended to decompress the portal circulation (1, 2). However, TIPS may not be suitable for some patients with poor hepatic reserve, portal vein thrombosis, hepatic encephalopathy, or severe thrombocytopenia (1-3). Balloon-occluded retrograde transvenous obliteration (BRTO) is an endovascular technique that was refined in Japan as a therVascular Plug-Assisted Retrograde Transvenous Obliteration for the Management of Gastric Varices: Comparative Effectiveness between Gelatin Sponge Embolization and Permanent Sclerosant 위정맥류 관리에서 Vascular Plug를 이용한 역행성 경정맥 폐쇄술의 효과: 젤폼을 사용한 색전술과 영구경화제의 효과 비교

Giant-Cell Arteritis: Immunopathogenic Mechanisms Involved in Vascular Inflammation and Remodeling

Giant-cell arteritis (GCA) is a large-vessel granulomatous vasculitis in which aging, gender and genetics likely play a significant role. The association with polymorphisms in the major histocompatibility complex suggests that GCA may be an antigen-driven disease. Immunopathology studies performed with temporal artery biopsies from patients with GCA have generated relevant clues regarding to pathogenesis by indicating participation of Th1 and Th17-mediated pathways, a prominent role for macrophages in tissue injury, and the relevance of vascular response to inflammation. Vascular wall elements, especially endothelial cells and vascular smooth muscle cells are not passive bystanders. Through expression of chemokines and adhesion molecules vascular cells contribute to the continuous recruitment of inflammatory cells that are able to enter the artery wall through newly formed neovessels. Inflammatory cell products, as well as vascular injury, trigger a vascular remodelling process. This eventually leads to the development of intimal hyperplasia and vascular lumen obliteration, source of ischemic complications.