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Glycocalyx lines the vascular intraluminal space that regulates fluid movement between the intra- and extra-vascular compartments. The depletion of glycocalyx (GCX) is associated with leukocyte accumulation, possibly causing the endothelial cells to become hyperpermeable in various organs, including oral tissues. Whether neutrophils or macrophages are responsible for developing interstitial edema remains controversial. We explored the pathophysiological mechanism of interstitial edema by examining the role of reactive neutrophils and macrophages and their interactions with GCX. An anti-MHC class I antibody was administered intravenously to male BALB/c mice to induce pulmonary edema. Pulmonary edema was evaluated by measuring the lung wet-to-dry weight ratio. Changes in the GCX were evaluated by electron microscopy and measurements of the serum level of soluble syndecan-1. Heparin sulfate was administered to examine its protective effect on the GCX. The macrophages were depleted using clodronate to examine their role in developing edema. The GCX degradation induced by the anti-MHC class I antibody was accompanied by increased serum syndecan-1 and heparan sulfate levels. Macrophage depletion inhibited the development of pulmonary edema, and the administration of supplemental heparin suppressed the edema. We demonstrated that the degradation of the GCX induced by the anti-MHC class I antibody was suppressed by macrophage depletion. These results suggest that macrophages may play a key role in interstitial edema. Heparin inhibited both the degradation of the GCX and interstitial edema. This study's results may be extrapolated to develop an interventional strategy for inhibiting interstitial edema in various organs. • The administration of anti-MHC class I antibody induced interstitial edema. • The GCX on the pulmonary vascular endothelium was degraded administered anti-MHC class I antibody. • Macrophage depletion prevented the development of interstitial edema, preserving the GCX. • Interstitial edema can be ameliorated by the administration of supplemental heparin. • The contribution of macrophages to glycocalyx degradation remains to be elucidated. [ABSTRACT FROM AUTHOR]

Objectives: Primary target of the study was identifying pulmonary interstitial edema (IE) with lung ultrasonography after open-heart surgery and searching the reasons of edema. Methods: At the end of the surgery, patients divided in two groups: Group Control: No IE and lung ultrasound (LUS) Score <17. Group IE: IE, LUS score ≥17. All clinical, hemodynamic data, and LUS score were recorded at the beginning (t0), at the end of surgery (t1 ), at post-operative 4th h (t2 ), 24th (t3 ), and 48th h (t4 ). Results: The mean LUS score of Group IE (n=32, 58%) was 20.8±4.3 and those of patients in Group C mean LUS skore (t1 ) of 16.2±3.7 (n=23, %42) points at the end of the surgery (t1 ). In Group IE, serum lactate level was higher than control group (respectively, 2.0±0.8, 1.6±0.8, p=0.04, p<0.02). There was statistically significant positive correlation between LUS scores at the postoperatively 4th h (t2 ) and central venous pressure (CVP) at the beginning (t0 ) (r=0.27 p=0.04). There was significantly positive correlation between LUS scores (t2 ) at the postoperatively 4th h and duration of stay in intensive care unit (ICU) (r=0.35 p<0.01). There was negative correlation between CVP at the beginning (t0) and the pump balance during cardiopulmonary by-pass (r=0.29 p=0.03). Conclusion: The values of CVP, post-operative serum lactate levels, and the length of stay in ICU are found higher in patients with pulmonary IE.The patients with IE had more negative fluid balance in cardiopulmonary bypass (CPB). The presence of diabetes and renal failure, type of surgery, ejection fraction, duration of cross-clamp and CPB did not associated with pulmonary edema in this study. Evaluation of pulmonary IE by lung US method after open heart surgery is valuable in terms of being able to be applied at the bedside, being non-invasive, and providing information about fluid balance. [ABSTRACT FROM AUTHOR]

High-altitude cerebral edema (HACE) and acute mountain sickness (AMS) are neuropathologies associated with rapid exposure to hypoxia. However, speculation remains regarding the exact etiology of both HACE and AMS and whether they share a common mechanistic pathology. This review outlines the basic principles of HACE development, highlighting how edema could develop from 1) a progression from cytotoxic swelling to ionic edema or 2) permeation of the blood brain barrier (BBB) with or without ionic edema. Thereafter, discussion turns to the available neuroimaging literature in the context of cytotoxic, ionic, or vasogenic edema in both HACE and AMS. Although HACE is clearly caused by an increase in brain water of ionic and/or vasogenic origin, there is very little evidence that this type of edema is present when AMS develops. However, cerebral vasodilation, increased intracranial blood volume, and concomitant intracranial fluid shifts from the extracellular to the intracellular space, as interpreted from changes in diffusion indices within white matter, are observed consistently in persons acutely exposed to hypoxia and with AMS. Therefore, herein we explore the idea that intracellular swelling occurs alongside AMS, and is a critical precursor to extracellular ionic edema formation. We propose that this process produces a subtle modulation of the BBB, which either together with or independent of vasogenic edema provides a transvascular segue from the end-stage of AMS to HACE. Ultimately, this review seeks to shed light on the possible processes underlying HACE pathophysiology, and thus highlights potential avenues for future prevention and treatment. [ABSTRACT FROM AUTHOR]

Introduction: The no-reflow phenomenon has been described in 20–40% of patients with acute ST-segment elevation myocardial infarction, despite restoration of TIMI 3 myocardial flow. It is associated with adverse left ventricular remodeling and an unfavorable long-term prognosis.

The lymphatic vasculature plays a key role in regulating tissue fluid homeostasis, lipid transport, and immune surveillance throughout the body. Although it has been appreciated that the heart relies on lymphatic vessels to maintain fluid balance and that such balance must be tightly maintained to allow for normal cardiac output, it has only recently come to light that the lymphatic vasculature may serve as a therapeutic target with which to promote optimal healing following myocardial ischemia and infarction. This article reviews the subject of cardiac lymphatic vessels and highlights studies that imply targeting of lymphatic vessel development or transport using vascular endothelial growth factor-C therapy may serve as a promising avenue for future clinical application in the context of ischemic injury.

Aim: Uterine atony is a major cause of postpartum hemorrhage. We recently proposed a new concept for the histopathophysiology of refractory uterine atony, postpartum acute myometritis (PAM), characterized by acute inflammatory changes with massive stromal edema, increased numbers of complement C5a receptors and diffuse mast cell activation in the myometrium. We herein focused on the possible involvement of the kinin‐kallikrein system in the rapid development of interstitial edema in PAM, particularly bradykinin receptor type 1 (B1R), which is up‐regulated under inflammatory conditions. The present study investigated B1R expression with uterine interstitial edema in PAM. Methods: Our institution plays an important role in a Japanese amniotic fluid embolism registry project. We selected PAM cases from uterine samples delivered to us for further analyses between 2012 and 2017. Control tissues were collected during cesarean section and planned hysterectomy. B1R expression was semi‐quantitatively measured by immunohistochemistry, while uterine interstitial edema was estimated by semi‐quantitative measurements of the alpha smooth muscle actin‐negative area using immunohistochemistry. Results: There were 36 and 8 cases in the PAM and control groups, respectively. The alpha smooth muscle actin‐negative area was increased in the PAM group, concomitant with the significant up‐regulation of B1R expression in uterine smooth muscle cells, vascular endothelial cells, and neutrophils. A positive correlation was observed between these two factors. Conclusion: We demonstrated the up‐regulated expression of B1R in the myometrium and its positive correlation with histologically estimated interstitial edema, suggesting the contribution of the kinin‐kallikrein‐B1R system to the development of interstitial edema in PAM cases. [ABSTRACT FROM AUTHOR]

Brain edema is defined as an increase in brain volume resulting from abnormal accumulation of fluid within the brain parenchyma. Brain edema is a potentially life-threatening complication of neurocritical illness as it raises the intracranial pressure and may progress to brain herniation and death. The management of brain edema and increased intracranial pressure is a significant challenge in neurocritical care. The purpose of this review is to describe the pathophysiology of diverse types of brain edema.

Purpose: We studied the relationship between type II pneumocytes number and alveolar septal thickness during different time after sublethal whole-thorax irradiation of rats and we investigated the influence of pentoxifylline (TNF-α inhibitor). Materials and methods: Wistar rats were exposed to 15 Gy thoracic irradiation and pentoxifylline (35 mg/kg) twice a week. Lungs were examined histologically and imunohistochemically at intervals ranging from 1-12 weeks and alveolar septal thickness, number of type II pneumocytes (identified by immunoreactivity for cytokeratin 18), and neutrophile granulocytes were counted. Results: Significant increase of alveolar septal thickness and type II pneumocytes depletion 3 weeks after irradiation were found. Correlation of these markers was r = -0.759. Pentoxifylline significantly inhibits increased alveolar septal thickness without the influence on type II pneumocytes number. Neutrophil penetration started 5 weeks after irradiation in non-treated animals, 8 weeks after irradiation in PTX-treated rats. Conclusions: We suggest that pneumocytes depletion is linked to increased vascular permeability, and pentoxifylline therapy does not influence on pneumocytes kinetics after irradiation.

Hydrocephalus is caused by an imbalance in cerebrospinal fluid (CSF) production and absorption, resulting in excess ventricular fluid accumulation and neurologic impairment. Current therapy for hydrocephalus involves surgical diversion of excess ventricular fluid. The water-transporting protein aquaporin-4 (AQP4) is expressed at the brain–CSF and blood–brain barriers. Here, we provide evidence for AQP4-facilitated CSF absorption in hydrocephalus by a transparenchymal pathway into the cerebral vasculature. A mouse model of obstructive hydrocephalus was created by injecting kaolin (2.5 mg/mouse) into the cisterna magna. Intracranial pressure (ICP) was ∼5 mm Hg and ventricular size <0.3 mm3 in control mice. Lateral ventricle volume increased to 3.7±0.5 and 5.1±0.5 mm3 in AQP4 null mice at 3 and 5 days after injection, respectively, significantly greater than 2.6±0.3 and 3.5±0.5 mm3 in wildtype mice (P<0.005). The corresponding ICP was 22±2 mm Hg at 3 days in AQP4 null mice, significantly greater than 14±1 mm Hg in wildtype mice (P<0.005). Brain parenchymal water content increased by 2% to 3% by 3 days, corresponding to ∼50 μL of fluid, indicating backflow of CSF from the ventricle into the parenchymal extracellular space. A multi-compartment model of hydrocephalus based on experimental data from wildtype mice accurately reproduced the greater severity of hydrocephalus in AQP4 null mice, and predicted a much reduced severity if AQP4 expression/function were increased. Our results indicate a significant role for AQP4-mediated transparenchymal CSF absorption in hydrocephalus and provide a rational basis for evaluation of AQP4 induction as a nonsurgical therapy for hydrocephalus.Journal of Cerebral Blood Flow & Metabolism (2006) 26, 1527–1537. doi:10.1038/sj.jcbfm.9600306; published online 22 March 2006 [ABSTRACT FROM AUTHOR]

The specific role of solid extracellular matrix components in opposing development of pulmonary interstitial edema was studied in adult anesthetized rabbits by challenging the lung parenchyma with an intravenous injection of a bolus of collagenase or heparanase. In 10 rabbits, pulmonary interstitial pressure (Pip) was measured by micropuncture in control and up to 3 h after collagenase or heparanase intravenous injection. With respect to control (Pip= ∼9.3 ± 1.5 cmH2O, n = 10), both treatments caused a significant increase of Pip and of the wet weight-to-dry weight lung ratio. However, while tissue matrix stiffness was maintained after 60 min of collagenase, as indicated by the attainment of a positive Pip peak (Pip= 4.5 ± 0.3 cmH2O, n = 5), this mechanical response was lost with heparanase (Pip= -0.6 ± 1.3 cmH2O, n = 5). Biochemical analysis performed on a separate rabbit group (n = 15) showed an increased extraction of uronic acid with both enzymes, indicating a progressive matrix fragmentation. Gel chromatography analysis of the proteoglycan (PG) families showed that 60 min of both enzymatic treatments left the large-molecular-weight PGs (versican) essentially unaffected. However, the heparan-sulfate PG fraction was significantly cleaved, as indicated by a significant increase of the smaller PG fragments with heparanase, but not with collagenase. Hence, present data suggest that the integrity of the heparan-sulfate PGs is required to maintain the three-dimensional architecture of the pulmonary tissue matrix and in turn to counteract tissue fluid accumulation in situations of increased fluid filtration. [ABSTRACT FROM AUTHOR]

Acute renal failure (ARF) is an uncommon but alarming complication of idiopathic nephrotic syndrome. The renal failure could be secondary to causes evident from the history and evaluation, such as severe intravascular volume depletion, acute tubular necrosis, allergic interstitial nephritis, bilateral renal vein thrombosis, acute pyelonephritis, or rapid progression of the original glomerular disease. It may be termed idiopathic if the underlying cause is undetermined. We present three children with idiopathic nephrotic syndrome who were admitted with acute renal failure. One case was due to drug-induced allergic interstitial nephritis. The other two were idiopathic in nature. Improvement in renal function occurred in the three patients over a variable period of 10 days to 4 weeks. After careful exclusion of well-known causes of acute renal failure, idiopathic acute renal failure (IARF) should be considered as a diagnostic possibility in these patients. The exact pathophysiology of IARF is not understood. Possible proposed explanations include interstitial edema, tubular obstruction, altered glomerular permeability, and unrecognized hypovolemia. [ABSTRACT FROM AUTHOR]

Background/Aim: Local blood flow failure (no-reflow phenomenon) during ischemia/reperfusion (I/R) injury may be mediated by interstitial edema formation (passive vasoconstriction) and/or microvascular spasm (active vasoconstriction). The development of the no-reflow phenomenon in the rabbit hind limb I/R model and the influence of treatment with L-arginine and/or antioxidative vitamins were investigated. Methods: Untreated rabbits were compared with those treated with L-arginine (4 mg/kg/min) or antioxidative vitamins (0.4 ml/kg) alone or in combination during hind limb I/R (2.5/2 h). Interstitial edema formation and microvessel diameter alterations were measured morphometrically. Capillary blood perfusion was measured continuously with laser Doppler flowmetry. Results: I/R injury was expressed by interstitial edema formation (interstitial space increase by 80%), microvascular constriction (microvessel crosssectional area decrease by 30%), and development of no-reflow phenomenon (blood flow reduction by 60%). Treatment with antioxidative vitamins alone or L-arginine alone reduced interstitial edema by 22 and 31%, consequently, while combined L-arginine/antioxidative vitamin treatment showed a more pronounced edema reduction by 40%. Treatment with only antioxidative vitamins failed to influence the development of no-reflow, although interstitial edema formation was reduced. L-Arginine treatment alone or in combination with antioxidative vitamins prevented microvascular constriction and preserved blood flow after reperfusion without development of no-reflow despite still apparent interstitial edema. Conclusions: Affections of active vasomotility and not merely passive changes of external pressure (i.e., interstitial edema formation) should be considered important in the development of microvascular constriction during 'no-reflow' phenomenon. [ABSTRACT FROM AUTHOR]

To investigate the molecular events taking place during the development of hydraulic interstitial edema, we analyzed by microarray and conventional molecular techniques the variation of gene expression in lung from rabbits treated with slow-rate saline infusions. This analysis indicates that even a condition characterized by a small increase in extravascular water can have a significant influence on the inflammatory milieu. In this regard, cytokines, in particular TNFα, can be considered early mediators capable of inducing secondary effects on the injured tissue. Moreover, two MT1 genes were strongly up-regulated, data consistent with their role as protective molecules. [Copyright &y& Elsevier]

: PurposeThe aim of this explorative study was to evaluate the impact of selenium in the treatment of lymphedema after radiotherapy.: Methods and materialsBetween June 1996 and June 2001, 12 patients with edema of the arm and 36 patients with edema of the head-and-neck region were treated with selenium for therapy-related lymphedema. Of these 36 patients, 20 had interstitial endolaryngeal edema associated with stridor and dyspnea. All patients received sodium selenite over 4 to 6 weeks.: ResultsSelf-assessment using a visual analog scale (n = 48) showed a reduction of 4.3 points when comparing pre- and posttreatment values (p < 0.05). Of 20 patients with endolaryngeal edema, 13 underwent no tracheostomy, 5 underwent a temporary tracheostomy, and only 2 underwent a permanent tracheostomy. Ten of 12 patients with arm edema showed a circumference reduction of the edematous limb and improvement in the Skin-Fold Index by 23.3 points. An improvement of one stage or more was shown by the Fo¨ldi or the Miller score (n = 28) in 22 (Fo¨ldi score) and in 24 (Miller score) patients.: ConclusionTreatment with sodium selenite is well tolerated and easy to deliver. Additionally, our results suggest that sodium selenite has a positive effect on secondary-developing lymphedema caused by radiation therapy alone or by irradiation after surgery. [Copyright &y& Elsevier]

Background and Objective: Systemic lupus erythematosus (SLE) is fairly common immunologic disorder, more common in females. Renal involvement in the form of nephritis is frequent with proteinuria, haematuria and even renal failure in uncontrolled cases. The objective of the present study was to assess the frequency of biopsy proven class I-V Lupus Nephritis at Fatima Memorial Hospital Lahore, which is a tertiary care teaching hospital. Methods: A descriptive study was conducted in the Department of Pathology at Fatima Memorial Hospital Lahore from January to December 2015. Both male and female patients with clinical suspicion of lupus nephritis having serum ANA and Anti-ds DNA level investigations were included. The staining methods performed for light microscopy were Hematoxylin and Eosin (HandE) in order to study the morphology and determine the frequency of five classes of Lupus Nephritis. Results: Among 38 patients, 18.4% were males and 81.6% were females which makes the male to female ratio, 1:5. Mean age of the patients was 26.55 ± 8.13 years with age range of 14 – 49 years. When the patients were assessed on the basis of biopsy by HandE staining, out of 38 patients, n = 05 belonged to class III, n = 32 belonged to class IV and n = 1 belonged to class V. Conclusions: Maximum number of the patients i.e. 84.21% were in class IV, then 13.16% were in class III and only 2.63% were in class V lupus nephritis. [ABSTRACT FROM AUTHOR]

The lymphatic vasculature plays a key role throughout the body in regulating tissue fluid homeostasis, lipid transport, and immune surveillance. Whereas it has been appreciated that the heart relies on lymphatic vessels to maintain fluid balance and that such balance must be tightly maintained to allow for normal cardiac output, it has only recently come to light that the lymphatic vasculature might serve as a therapeutic target to promote optimal healing following myocardial ischemia and infarction. We review the subject of cardiac lymphatic vessels herein and highlight studies that imply targeting of lymphatic vessel development or transport may serve as a promising avenue for future clinical application in the context of ischemic injury.

Vascular surgery patients frequently suffer from atherosclerosis and peripheral arterial occlusive disease generating endothelial dysfunction. Furthermore, ischemia and reperfusion during surgery damage endothelial cells and, especially, the endothelial glycocalix. The damage of the glycocalix promotes an increase in permeability. Not only crystalloids, which freely diffuse between the intravascular and the interstitial compartment, but also colloidal fluids cross from the intravascular space in the interstitial space with the consequence of edema formation. Possible tissue edema may result in an impairment of tissue oxygenation, leading to wound healing disturbances and initiation of inflammatory responses up to tissue apoptosis. Particularly in vascular anesthesia, this possibly means that colloids only should be administered in acute volume resuscitation immediately after unclamping a big vessel for immediate volume restoration. Which colloidal fluid should be administered is still under intense discussion. From a theoretical physiologic point of view, iso-osmolar albumin is the best choice regarding volume effect, antioxidative properties, and protection against destruction of the glycocalix. Nonetheless, albumin experimentally has not lived up to its promise in the clinical setting. Thus, further well-conducted large randomized clinical trials are necessary to ascertain the optimal fluid therapy in vascular surgery patients.

Background: There are few reports on the precise electrocardiographic characteristics of acute myocarditis. The present study was focused on QRS voltage changes at the superacute stage of murine myocarditis., Methods: Serial electrocardiograms were recorded during the acute stage of viral myocarditis in mice, and then the cardiac pathology was examined. After recording baseline electrocardiograms, mice (n=235) were inoculated intraperitoneally with the encephalomyocarditis virus, resulting in severe myocarditis. Electrocardiograms were serially recorded until nine days after virus inoculation (superacute stage, days 3 to 6; acute stage, days 7 to 9). Changes in heart rate and QRS voltages were analyzed., Results: Serial electrocardiograms revealed that heart rates began to increase after day 3, and that the sum of the QRS voltages increased on day 3 and then decreased on days 7 to 9. Trivial mononuclear cell infiltrations and interstitial edema were most frequently found in mice at the superacute stage., Conclusions: Transient increase of the QRS voltages at the superacute stage of myocarditis was demonstrated, which may be due to an increase in ventricular mass caused by interstitial edema at this stage.