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Recent discoveries have identified intrapulmonary bronchopulmonary anastomoses (IBAs) as a relatively common phenomenon forming intrapulmonary right-to-left shunts. This study hypothesizes that IBAs play a significant role in the pathophysiology of heart failure. We aim to investigate the impact of these intrapulmonary right-to-left shunts on pulmonary arterial and venous pressures in heart failure patients, utilizing mixed venous oxygen saturation (SvO₂) as a key measurement. This study included 237 patients with heart failure who underwent cardiac catheterization. The relationships between SvO₂ and pulmonary artery systolic pressure (sPAP), pulmonary artery wedge pressure (PAWP), and left ventricular end-diastolic pressure (LVEDP) were examined using various statistical methods (single regression analysis, partial correlation analysis, structural equation modeling, and Bayesian estimation). All statistical methods that we performed showed that SvO₂ was significantly and negatively correlated with both sPAP and PAWP (p < 0.01, respectively). However, SvO₂ did not significantly correlate with LVEDP. These results suggest that a decrease in SvO₂ leads to an increase in PAWP and sPAP, while LVEDP is only passively influenced by PAWP. This phenomenon likely reflects the impact of an intrapulmonary right-to-left shunt caused by IBAs. The decrease in SvO₂ causes an increase in sPAP and may also cause an increase in PAWP via IBAs., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: To study the correlation between episcleral vein pressure (EVP) with intraocular pressure (IOP), exophthalmos, and optic nerve injury in thyroid-associated ophthalmopathy (TAO) patients and to explore the possibility of higher EVP as an intervention indicator in TAO patients., Methods: This study was a case-control study, including the TAO group and normal control group. TAO group: 15 patients (30 eyes) were diagnosed with TAO complicated with exophthalmos. Normal control group: 14 cases, 28 eyes. EVP, IOP, exophthalmos, retinal nerve fiber layer thickness, and visual field were measured, respectively in the two groups. Non-parametric test was used to compare the difference between EVP and IOP between the two groups, test the correlation between EVP and IOP or exophthalmos, and analyze the clinical characteristics of optic nerve injury in patients with elevated IOP in the TAO group., Results: The EVP in the TAO group (15.30±3.48 mmHg) was significantly higher than the normal control group (8.82±1.44 mmHg) (P < .001). The IOP in the TAO group (18.55±8.13 mmHg) was significantly higher than in the normal control group (12.98±2.10 mmHg) (P < .001) (3) There was a positive linear correlation between EVP (X) and IOP (Y) in TAO group: Y = 0.9684x + 3.737 (rs>0, P < .05); There was a positive linear correlation between EVP (Y) and exophthalmos (X) in TAO group: Y = 0.9218x - 2.691 (rs>0, P < .05); Some TAO patients with elevated EVP had the related manifestations of optic nerve function impairment: thinning of retinal nerve fiber layer and loss of visual field. However, there was no clear correlation between EVP and the thickness of the optic nerve fiber layer (P = .4354)., Conclusion: The increase of EVP is an important factor leading to elevated IOP in TAO patients, which may be used as an indicator for intervention treatment in TAO patients. EVP can be used to indirectly evaluate orbital pressure. TAO patients can develop secondary glaucoma with irreversible optic nerve damage due to the continuous Elevation of EVP.

Background: Idiopathic intracranial hypertension (IIH) is a cause of chronic headaches that are probably driven by raised intracranial pressure (ICP). Cerebral venous sinus pressure is thought to play a role in the underlying pathology, but its relation with intracranial pressure requires further investigation. We aimed to evaluate the concordance between lumbar puncture opening pressure (LPOP) as indicator of the ICP and cerebral venous sinus pressure in patients investigated for IIH., Methods: In this case-series replication study, all patients with IIH suspicion and who underwent cerebral venous sinus pressure measurement followed immediately by LP opening pressure (LPOP) measurement were retrospectively included. Pearson's correlation and measurement agreement (Bland-Altman plots) between venous pressure and LPOP were analyzed., Results: 52 consecutive patients (46 women; median age, 31 years [IQR = 25-42]) were included. The mean pressure in the superior sagittal sinus (SSS) and in the torcular were 20.9mmHg (SD ± 7.3) and 20.8 mmHg (SD ± 6.8), respectively. The mean LPOP was 22mmHg (SD ± 6.4). Pressure measured in the transverse venous sinus, the torcular, and the SSS correlated with LPOP (p < 0.001). Bland-Altman plots showed that torcular pressure strongly agreed with LPOP (mean difference of 1.7mmHg). The limit of agreement (LOA) (mean difference ± 1.96SD) contained 98.1% of the differences between the two methods, confirming the concordance between the two measures. Torcular pressure and LPOP were consistent in patients with a trans-stenotic pressure gradient ≥ or < to 8 mmHg (mean difference: 1mmHg and 2.4mmHg, respectively), and for those with a LP OP ≥ or < to 18mmHg (mean difference: 1.8mmHg and 1.95mmHg, respectively)., Conclusions: In patients investigated for IIH, the ICP measured at the LP is correlated and concordant with the torcular pressure. These results confirm previous findings and further corroborate the hypothesis that cerebral venous system plays a major role in CSF dynamics and ICP., (© 2024. The Author(s).)

Purpose: This study is to investigate the increase in retinal venous pressure (RVP) induced by a stepwise increase in airway pressure (AirP) using the new IOPstim method, which is designed to artificially increase the intraocular pressure (IOP) and thus to stimulate vascular pulsation., Methods: Twenty-eight healthy subjects were examined in the left eye. The RVP was measured at baseline and at four different levels of AirP (10, 20, 30, and 40 mmHg) using the new IOPstim method: a half balloon of 8 mm diameter is inflated laterally to the cornea under observation of the central retinal vein. As soon as the vein pulsates at a certain AirP level, the IOP is measured with a commercially available tonometer, which then corresponds to the RVP., Results: Spontaneous venous pulsation was observed in all study participants. The mean RVP values at baseline and at the AirP levels of 10, 20, 30, and 40 mmHg were 17.6 ± 2.8 mmHg; 20.1 ± 3.0 mmHg; 22.1 ± 3.5 mmHg; 24.3 ± 3.7 mmHg, and 26.6 ± 4.2 mmHg, respectively. The mean RVP values of each AirP level were statistically significantly different from each other in pairwise comparison. In a linear mixed model, the effect of AirP on RVP was highly significant (p < 0.001). In the model, a 10-mmHg increase in AirP resulted in a linear increase in RVP of 2.2 mmHg., Conclusion: An increase in AirP was accompanied by a linear increase in RVP. The influence of AirP on RVP, and thus on retinal perfusion pressure during the Valsalva maneuver, is less than was assumed based on previous studies in which contact lens dynamometry was used., (© 2024. The Author(s).)

Background: Pediatric idiopathic intracranial hypertension (IIH) is a rare and challenging condition. As implied by the nomenclature, the etiologies remain unknown, and multiple etiologies are being investigated. In this study, we explored the potential role of increased systemic or cerebral venous pressure in the pathogenesis., Method: An observational cohort study following the STROBE guidelines, including prepubertal children with clinical symptoms and imaging findings consistent with IIH referred to the neurosurgical department, was conducted. The patients underwent a comprehensive diagnostic protocol, including MRI, continuous intracranial pressure (ICP) monitoring, and endovascular venography with venous pressure measurements., Results: The study included 11 consecutive patients (six boys and five girls) with an average age of 2.3 years, and an average BMI of 18.4. Among these, one patient was found to have venous stenosis with a gradient; the other 10 patients presented with normal intracranial anatomy. All patients exhibited elevated venous pressures, with an average superior sagittal sinus pressure of 18.9 mmHg, average internal jugular vein pressure of 17.0 mmHg, and average central venous pressure of 15.9 mmHg. Daytime ICP averaged 12.9 mmHg, whereas nighttime ICP averaged 17.2 mmHg with either A- or B-waves in 10 of the 11 patients. Despite pathological ICP, only three patients had papilledema., Conclusions: All patients had an increased systemic venous pressure, indicating a possible pathological factor for prepubertal IIH. Additionally, our findings show that young children often only partly meet the Friedman criteria due to a lack of papilledema, emphasizing the need for pediatric-specific diagnostic criteria. Further large-scale studies are needed to confirm these findings and to explore the underlying reasons for this increase in venous pressure and potential new treatment avenues., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose of Review: Venous pressure is an often-unrecognized cause of patient morbidity. However, bedside assessment of PV is challenging. We review the clinical significance of venous pressure measurement, existing techniques, and introduce the Venous Excess Ultrasound (VExUS) Score as a novel approach using doppler ultrasound to assess venous pressure., Recent Findings: Studies show clear associations between elevated venous pressure and adverse outcomes in critically ill patients. Current venous pressure measurement techniques include physical examination, right heart catheterization (RHC), two-dimensional ultrasound, and a variety of labor-intensive research-focused physiological maneuvers. Each of these techniques have specific shortcomings, limiting their clinical utility. To address these gaps, Beaubien-Souligny et al. introduced the VExUS Score, a novel doppler ultrasound-based method that integrates IVC diameter with doppler measurements of the hepatic, portal, and renal veins to generate a venous congestion assesment. Studies show strong correlations between VExUS score and RHC measurements, and well as an association between VExUS score and improvement in cardiorenal acute kidney injury, diuretic response, and fluid status shifts. However, studies in noncardiac populations have been small, heterogenous, and inconclusive., Summary: Early studies evaluating the use of doppler ultrasound to assess venous congestion show promise, but further research is needed in diverse patient populations and clinical settings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study aims to explore factors that affect venous sinus pressures and associated gradients while awake and under general anesthesia (GA) both before and after venous sinus stenting (VSS) in patients with idiopathic intracranial hypertension (IIH)., Methods: A retrospective analysis was performed examining pressures and gradients in patients with IIH having undergone awake venography followed by VSS under GA., Results: 174 patients were included. Compared with awake, GA superior sagittal sinus (SSS) pressures were 2.6 mmHg lower (p=0.01) resulting in a total cranial gradient reduction of 2.5 mmHg (p=0.002). The transverse-sigmoid gradient, the most commonly stented segment, did not differ under the two conditions (p=0.30). Regression analyses demonstrated that body mass index, gender, blood pressure, and end-tidal carbon dioxide content significantly affected venous pressures (all p<0.05). After stenting, mean total cranial gradients decreased by 13.2 mmHg while skull base gradients increased by 0.8 mmHg. Stenting resulted in an 84% mean reduction in the target gradient and a mean decrease in SSS pressures by 78% of the target gradient. When cardiopulmonary and anesthetic factors were optimized, GA had a limited effect on the target gradient in most patients (p=0.88)., Conclusions: This study is the largest series to date to report on cerebral venous pressure measurements and gradients recorded while awake and under GA both before and after VSS for IIH. In a well-controlled cardiorespiratory and anesthetic setting, GA venography may provide information that is not substantially inequivalent to that obtained while awake., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The delicate interplay between the muscle-joint unit and intact venous valves is mandatory for normal venous blood return from the human leg. We have investigated the potential role of (1) muscle activity and joint mobility, and (2) anthropometric factors for peripheral venous pressure physiology. 20 healthy young subjects (10 males, 10 females; mean age: 25.6 ± 3.1 years) underwent direct venous blood pressure measurements during walking on a treadmill in 12 experimental conditions (duration, 1 min each): these resulted from a combination of two different walking velocities, two different degrees of ascent, and three different walking conditions. Anthropometric parameters (e.g., body height, weight and calf circumference) were also measured in all subjects. Outcome measures were the pressures (mm Hg) during quiet standing (resting pressure, P[sub 0] ), the maximal activity-induced pressure reduction (ΔP[sub max] ), i.e., the difference between the resting pressure (P[sub 0] ) and minimal pressure during exercise (P[sub min] ), the times (s) to minimal pressure during exercise (T[sub Pmin] ) and to half-maximal recovery of P[sub 0] after exercise (T[sub max1/2] ). We found that the maximal venous pressure reduction (ΔP[sub max] ) during walking increased at the higher walking speed and decreased with restricted joint mobility (p = 0.0001). Taller and heavier subjects, or subjects with a greater calf circumference had higher P[sub 0] (p = 0.0001), showed greater ΔP[sub max] (p < 0.010), and took longer to achieve minimal pressure during exercise (T[sub Pmin] ; p < 0.010) than their corresponding counterparts. Females had lower levels of P[sub 0] (p = 0.0001), but not of ΔP[sub max] , and shorter T[sub Pmin] (p = 0.0076) than males. These gender effects largely result from differences in body height, weight, and calf circumference (p = 0.0001 for the appropriate ANOVA interaction terms). We conclude that during walking, a higher degree of muscle activity and a greater muscle mass enhance venous emptying of the healthy human leg. Conversely, impairments of joint mobility reduce the efficacy of the muscle-vein pump. Moreover, body height and weight significantly influence venous pressure physiology under both resting and activity-related conditions. These anthropometric factors also largely explain sex differences in peripheral venous hemodynamics.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The retinal venous pressure (RVP) is a determining factor for the blood supply of the retina as well as the optic nerve head and until recently has been measured by contact lens dynamometry (CLD). A new method has been developed, potentially offering better acceptance. The applicability and the results of both methods were compared., Methods: The type of this study is cross sectional. The subjects were 36 healthy volunteers, age 26 ± 5 years (mean ± s). Tonometry: rebound tonometer (RT) (iCare). The measurements were performed during an increase in airway pressure of 20 mmHg (Valsalva manoeuvre). Principle of RVP measurement: the central retinal vein (CRV) is observed during an increase of intraocular pressure (IOP) and at the start of pulsation, which corresponds with the RVP. Two different instruments for the IOP enhancement where used: contact lens dynamometry and the new instrument, IOPstim., Principle: a deflated balloon of 8 mm diameter-placed on the sclera laterally of the cornea-is filled with air. As soon as a venous pulsation occurs, filling is stopped and the IOP is measured, equalling the RVP. Examination procedure: randomization of the sequence: CLD or IOPstim, IOP, mydriasis, IOP three single measurements (SM) of the IOP with RT or of the pressure increase with CLD at an airway pressure of 20 mmHg, 5 min break, IOP, and three SM using the second method at equal pressure (20 mmHg)., Results: Spontaneous pulsation of the CRV was present in all 36 subjects. Pressures are given in mmHg. IOP in mydriasis 15.6 ± 3.3 (m ± s). Median RVP (MRVP)) of the three SM: CLD/IOPstim, 37.7 ± 5.2/24.7 ± 4.8 (t test: p < 0.001). Range of SM: 3.2 ± 1.8/2.9 ± 1.3 (t test: p = 0.36). Intraclass correlation coefficient (ICC) of SM: 0.88/0.83. ANOVA in SM: p = 0.48/0.08. MRVP CLD minus MRVP IOPstim: 13.0 ± 5.6. Ratio MRVP CLD/MRVP IOPstim: 1.56 ± 3.1. Cooperation and agreeability were slightly better with the IOPstim., Conclusion: This first study with the IOPstim in humans was deliberately performed in healthy volunteers using Valsalva conditions. As demonstrated by ICC and ANOVA, reproducible SM can be obtained by both methods and the range of the SM does not differ greatly. The higher MRVP in CLD could be explained by the different directions of the force vectors., (© 2021. The Author(s).)

Introduction: Until now, venous pressure within the eye has widely been equated with intraocular pressure (IOP). Measurements with dynamometers calibrated in instrument units or in force showed that the retinal venous pressure (RVP) may be higher than the IOP in glaucoma patients. In this study, the RVP was measured with a contact lens dynamometer calibrated in mmHg., Methods: Study type: cross-sectional., Subjects: Fifty consecutive patients with primary open-angle glaucoma (POAG) who underwent diurnal curve measurement under medication. Age: 69 ± 8 years. Measurement of RVP: contact lens dynamometry. IOP measurement: dynamic contour tonometry., Results: Pressures are given in mmHg. In all 50 patients, the IOP was 15.9 (13.6; 17.1) [median (Q1; Q3)], and the RVP was 17.4 (14.8; 27.2). The distribution of the IOP was normal and that of the RVP was right skewed. In the subgroup of 34 patients with spontaneous pulsation of the central retinal vein (SVP), the IOP and therefore, by definition, the RVP was 16.5 (13.7; 17.4). In the subgroup of 16 patients without SVP, the IOP was 14.8 (13.3; 16.4), and the RVP was 31.3 (26.2; 38.8) (p ≤ 0.001). In systemic treatment, the prescribed drugs were (the number of patients is given in parentheses): ACE inhibitors (20), β -blockers (17), angiotensin II-receptor blockers (13), calcium channel blockers (12), diuretics (7). No difference in RVP was observed between patients receiving these drugs and not receiving them, except in the β -blocker group. Here, the 17 patients with systemic β -blockers had a median RVP of 15.6 mmHg and without 20.2 mmHg (p = 0.003). In the 16 patients with a higher RVP than IOP, only one patient received a systemic β -blocker. The median IOP was 15.7 mmHg with systemic β -blockers and 16.1 mmHg without (p = 0.85)., Conclusion: In a subgroup of 16 of the 50 patients studied, the RVP was greater than the IOP by a highly statistically and clinically significant degree. According to the widely accepted thinking on the pathophysiology of retinal and optic nerve head circulation, the blood flow in these tissues may be much more compromised in this group of patients than has been assumed. They may be identified by a missing SVP. Topical and systemic medications showed no statistically significant influence on the RVP, except for the systemic β -blockers, in which the RVP was lower by 4.6 mmHg than for the patients who did not receive these drugs (p = 0.003)., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: The treatment of hydrocephalus has been a topic of intense research ever since the first clinically successful use of a valved cerebrospinal fluid shunt 72 years ago. While ample studies elucidating different phenomena impacting this treatment exist, there are still gaps to be filled. Specifically, how intracranial, intrathecal, arterial, and venous pressures react and communicate with each other simultaneously., Methods: An in-vivo sheep trial (n = 6) was conducted to evaluate and quantify the communication existing within the cranio-spinal, arterial, and venous systems (1 kHz sampling frequency). Standardized intrathecal infusion testing was performed using an automated infusion apparatus, including bolus and constant pressure infusions. Bolus infusions entailed six lumbar intrathecal infusions of 2 mL Ringer's solution. Constant pressure infusions were comprised of six regulated pressure steps of 3.75 mmHg for periods of 7 min each. Mean pressure reactions, pulse amplitude reactions, and outflow resistance were calculated., Results: All sheep showed intracranial pressure reactions to acute increases of intrathecal pressure, with four of six sheep showing clear cranio-spinal communication. During bolus infusions, the increases of mean pressure for intrathecal, intracranial, arterial, and venous pressure were 16.6 ± 0.9, 15.4 ± 0.8, 3.9 ± 0.8, and 0.1 ± 0.2 mmHg with corresponding pulse amplitude increases of 2.4 ± 0.3, 1.3 ± 0.3, 1.3 ± 0.3, and 0.2 ± 0.1 mmHg, respectively. During constant pressure infusions, mean increases from baseline were 14.6 ± 3.8, 15.5 ± 4.2, 4.2 ± 8.2, and 3.2 ± 2.4 mmHg with the corresponding pulse amplitude increases of 2.5 ± 3.6, 2.5 ± 3.0, 7.7 ± 4.3, and 0.7 ± 2.0 mmHg for intrathecal, intracranial, arterial, and venous pulse amplitude, respectively. Outflow resistances were calculated as 51.6 ± 7.8 and 77.8 ± 14.5 mmHg/mL/min for the bolus and constant pressure infusion methods, respectively-showing deviations between the two estimation methods., Conclusions: Standardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample, and to the venous side in individual cases. These results represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems., (© 2021. The Author(s).)

Objective: To compare and validate umbilical venous flow volume (UVFV) measured at the intra-abdominal portion using ultrasound with actual flow volume of umbilical vein (UV) in fetal sheep sustained on the EXTrauterine Environment for Neonatal Development (EXTEND) system., Methods: Circuit flow volume through the oxygenator was obtained using sensors. Ultrasound derived UVFV (ml/min) was calculated as (UV diameter [cm]/2) 2 × 3.14 × maximum velocity (cm/s) × 0.5 × 60, measured at approximately the mid portion between its abdominal insertion and the origin of the ductus venosus. UVFV was measured by ultrasound once daily and was compared to the average of daily circuit flow volume directly measured., Results: UVFV was measured 168 times in 15 fetal sheep. The ratio of circuit flow volume to combined cardiac output remained stable within the anticipated physiological range throughout. UVFV measured by ultrasound showed good correlation to directly measured circuit flow (r = 0.72). Interclass correlation coefficients for intra-observer variability was 0.991 (95% confidence interval [CI], 0.979-0.996)., Conclusion: UVFV measured at the intra-abdominal portion using ultrasound shows a good correlation with directly measured circuit flow volume in UV of fetal sheep on the EXTEND system. Regular incorporation of such validated UVFV measures into clinical use may offer opportunities to better understand conditions of placental dysfunction., (© 2021 John Wiley & Sons Ltd.)

Episcleral venous pressure (EVP) is important for steady state intraocular pressure (IOP), as it has to be overcome by aqueous humor in order to leave the eye. Recent evidence suggests a neuronal tone being present, as topical anesthesia lowered EVP. The superior salivatory nucleus in the brainstem could be identified to elicit increases in EVP during electrical stimulation. In the present study the effect of topical anesthesia on the stimulation effect was investigated. 8 Spraque Dawley rats were anesthetized, artificially ventilated with CO2 monitoring and continuous blood pressure monitoring. Intraocular pressure was measured continuously through a cannula in the vitreous body. Episcleral venous pressure was measured by direct cannulation of an episcleral vein via a custom made glass pipette connected to a servonull micropressure system. Electrical stimulation of the superior salivatory nucleus (9 μA, 200 pulses of 1 ms duration) increased EVP from 8.51 ± 1.82 mmHg to 10.97 ± 1.93 mmHg (p = 0.004). After application of topical lidocaine EVP increased from 7.42 ± 1.59 mmHg to 9.77 ± 1.65 mmHg (p = 0.007). The EVP response to stimulation before and after lidocaine application was not statistically significantly different (2.45 ± 0.5 vs 2.35 ± 0.49 mmHg, p = 0.69), while the decrease in baseline EVP was (8.51 vs. 7.42 mmHg, p = 0.045). The present data suggest that distinct neuronal mechanisms controlling the episcleral circulation of rats exist. This is in keeping with previous reports of two distinct arterio-venous anastomoses, one in the limbal circulation and one in the conjunctival/episcleral circulation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: The noninvasive measurement of venous wall deformation induced by changes in transmural pressure could allow for the assessment of viscoelasticity and differentiating normal from diseased veins., Methods: In 57 patients with limbs in the C1s (telangiectasia or reticular veins and symptoms), C3 (edema), or C5 (healed venous ulcer) CEAP (clinical, etiologic, anatomic, pathophysiologic) category of chronic venous disease and 54 matched healthy controls, we measured the changes in the cross-sectional area of the small saphenous vein and a deep calf vein in the supine and standing positions and under compression with an ultrasound probe using ultrasonography., Results: The small saphenous vein, but not the deep calf vein, cross-sectional area was smaller in the limbs of the controls than in the limbs with C3 or C5 disease but was not different from that in C1s limbs. When changing from the supine to the standing position, a greater force was required to collapse the leg veins. Their cross-sectional area increased in most subjects but decreased in 31.5% of them as for the small saphenous veins and 40.5% for the deep calf vein. The small saphenous vein area vs compression force function followed a hysteresis loop, demonstrating viscoelastic features. Its area, which represents the viscosity component, was greater (P < .001) in the pooled C3 and C5 limbs (median, 2.40 N⋅mm 2 ; lower quartile [Q1] to upper quartile [Q3], 1.65-3.88 N⋅mm 2 ) than in the controls (median, 1.24 N⋅mm 2 ; Q1-Q3, 0.64-2.14 N⋅mm 2 ) and C1s limbs (median, 1.15 N⋅mm 2 ; Q1-Q3, 0.71-2.97 N⋅mm 2 ). The area increased (P < .0001) in the standing position in all groups., Conclusions: Postural changes in the cross-sectional area of the leg veins were highly diverse among patients with chronic venous disease and among healthy subjects and appear unsuitable for pathophysiologic characterization. In contrast, small saphenous vein viscoelasticity increased consistently in the standing position and the viscosity was greater in limbs with C3 and C5 CEAP disease than in controls., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Although Guyton's graphical analysis of cardiac output-venous return has become a ubiquitous tool for explaining how circulatory equilibrium emerges from heart-vascular interactions, this classical model relies on a formula for venous return that contains unphysiological assumptions. Furthermore, Guyton's graphical analysis does not predict pulmonary venous pressure, which is a critical variable for evaluating heart failure patients' risk of pulmonary edema. Therefore, the purpose of the present work was to use a minimal closed-loop mathematical model to develop an alternative to Guyton's analysis. Limitations inherent in Guyton's model were addressed by 1 ) partitioning the cardiovascular system differently to isolate left ventricular function and lump all blood volumes together, 2 ) linearizing end-diastolic pressure-volume relationships to obtain algebraic solutions, and 3 ) treating arterial pressures as constants. This approach yielded three advances. First, variables related to morbidities associated with left ventricular failure were predicted. Second, an algebraic formula predicting left ventricular function was derived in terms of ventricular properties. Third, an algebraic formula predicting flow through the portion of the system isolated from the left ventricle was derived in terms of mechanical properties without neglecting redistribution of blood between systemic and pulmonary circulations. Although complexities were neglected, approximations necessary to obtain algebraic formulas resulted in minimal error, and predicted variables were consistent with reported values.

Background and Aims: Nonselective beta-blockers (NSBBs) are the main drug to prevent portal hypertension. It could alter free hepatic venous pressure (FHVP); however, the significance is unknown. This prospective study was to explore the change of FHVP after use of NSBBs and its predictive value for gastroesophageal varices (GOV) bleeding in cirrhotic patients. Patients and Methods . Cirrhotic patients with medium-large GOV between September 2014 and January 2019 were enrolled. After initial hepatic venous pressure gradient (HVPG) measurement, patients received oral NSBBs. Seven days later, the secondary HVPG was examined to evaluate the FHVP alteration and hemodynamic response. The variceal bleeding between patients with FHVP increased and decreased/unchanged was compared., Results: A total of 74 patients were enrolled, and 62 patients completed the secondary HVPG measurement and was followed up. The cumulative bleeding rate was significantly higher in patients with FHVP increased ≥ 1.75 mmHg than those with FHVP decreased/unchanged (54.5% vs. 22.5%, p = 0.021), while there was no significant difference in bleeding between HVPG responders and nonresponders (32.6% vs. 37.5%, p = 0.520). For HVPG responders, variceal bleeding in patients with FHVP increased ≥ 1.75 mmHg was significantly more than that in patients with FHVP decreased/unchanged (57.9% vs. 28.6%, p = 0.041). Cox regression analysis showed that change of FHVP was an independent predictor of variceal bleeding., Conclusion: Increase ≥ 1.75 mmHg in FHVP responding to beta-blockers in cirrhotic patients with GOV indicates high risk of variceal bleeding. Besides HVPG response, change of FHVP should also be valued in hemodynamic evaluation to beta-blockers. This trial is registered with Chinese Clinical Trial Registry ChiCTR-IPR-17012836., Competing Interests: The authors declare that there are no conflicts of interest in this study., (Copyright © 2021 Huiwen Guo et al.)

Purpose: Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model., Methods: In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5-9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables., Results: With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (β = 0.31; 95% CI 0.14-0.48, p < .001), intraocular pressure (β = 0.37, 95%CI 0.24-0.50; p < .001) and retinal vein diameter (β = 11.29, 95%CI 1.57-21.00; p = .03) after controlling for the effects of arterial blood pressure., Conclusion: We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma.

Background: This study aimed to investigate changes in the hepatic venous pressure gradient (HVPG) by partial splenic embolization (PSE) and to identify the determinants of a clinically meaningful postoperative HVPG reduction., Methods: Sixty-eight patients with cirrhosis and hypersplenism who underwent PSE at our department between September 2007 and June 2020 were included. The HVPG was evaluated pre- and immediately post-PSE. The patients were divided into three groups according to their preprocedural HVPG: low-HVPG (< 10 mmHg, n = 22), intermediate-HVPG (10 mmHg ≤ HVPG < 16 mmHg, n = 33), and high-HVPG (≥ 16 mmHg, n = 13)., Results: Overall, PSE significantly reduced HVPG from 12.2 ± 4.0 to 9.4 ± 3.6 mmHg (p < 0.01) with a relative decrease of 22.2 ± 20.4%. In addition, HVPG reductions were 19.4 ± 28.7%, 24.0 ± 15.9%, and 22.5 ± 13.3% in the low-, intermediate-, and high-HVPG groups, respectively, indicating no significant difference in HVPG reduction between the groups. An HVPG decrease of ≥ 20% from the baseline, defined in this study as a clinically significant HVPG response to PSE, was achieved in 55.9% of all patients. Multivariate logistic regression and receiver operating characteristic curve analyses identified splenic non-infarction volume as an independent determinant of a 20% decrease in HVPG (p < 0.05), with a cut-off of 139.2 cm 3 (sensitivity, 76.3%; specificity, 60.0%; p < 0.05)., Conclusions: The splenic non-infarction volume, namely the residual functional spleen volume, independently determines a clinically significant HVPG response to PSE in patients with cirrhosis and hypersplenism.

Background: Pancreaticoduodenectomy with porto-mesenterico-splenic confluence resection can cause sinistral portal hypertension (SPH), which may lead to gastrointestinal bleeding. Nevertheless, it remains difficult to predict SPH development during surgery. The aim of this study is to assess the feasibility of measuring splenic vein (SV) pressure to predict SPH., Methods: The patients who underwent pancreaticoduodenectomy with porto-mesenterico-splenic confluence resection between January 2016 and December 2017 were included in this study. SV pressure was measured before SV clamping (SVP1) and after SV clamping (SVP2). SPH was defined as varicose vein formation detected by follow-up computed tomography. Incidence of SPH was assessed in patients who had no SV drainage after surgery., Results: SV pressure was measured in 41 patients. Among them, 24 had no SV drainage (13 patients had occluded SV reconstruction, and 11 had SV ligation without an attempt at reconstruction) and were included for the analysis. SPH was observed in 16 of 24 patients (67%). The median ΔSVP (SPV2-SVP1) in patients with SPH was higher than that in patients without SPH (13.5 mmHg versus 7.5 mmHg, P = 0.0237). Most patients with SVP2 >20 mmHg (12/14 [86%]) or ΔSVP >10 mmHg (10/11 [91%]) developed SPH., Conclusions: For the patients with SV resection, high SV pressure after clamping (≥20 mmHg) and a large SV pressure difference (≥10 mmHg) before and after clamping are feasible indication criteria for SV reconstruction to prevent SPH., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Glaucoma is a neurodegenerative disease of the eye with an estimated prevalence of more than 111.8 million patients worldwide by 2040, with at least 6 to 8 million projected to become bilaterally blind. Clinically, the current method of slowing glaucomatous vision loss is to reduce intraocular pressure (IOP). In this manuscript, we describe the in vitro cytoprotective and in vivo long lasting IOP-lowering activity of the poly D, L-lactic-co-glycolic acid (PLGA) nanoparticle-encapsulated hybrid compound SA-2, possessing nitric oxide (NO) donating and superoxide radical scavenging functionalities., Methods: Previously characterized primary human trabecular meshwork (hTM) cells were used for the study. hTM cells were treated with SA-2 (100 µM, 200 µM, and 1,000 µM), SA-2 PLGA-loaded nanosuspension (SA-2 NPs, 0.1%), or vehicle for 30 min. Cyclic guanosine monophosphate (cGMP) and super oxide dismutase (SOD) levels were analyzed using commercial kits. In another experiment, hTM cells were pretreated with tert -butyl hydrogen peroxide (TBHP, 300 µM) for 30 min followed by treatment with escalating doses of SA-2 for 24 h, and CellTiter 96 cell proliferation assay was performed. For the biodistribution study, the cornea, aqueous humor, vitreous humor, retina, choroid, and sclera were collected after 1 h of administration of a single eye drop (30 μl) of SA-2 NPs (1% w/v) formulated in PBS to rat (n = 6) eyes. Compound SA-2 was quantified using high performance liquid chromatography /mass spectrometry (HPLC/MS). For the IOP-lowering activity study, a single SA-2 NPs (1%) eye drop was instilled in normotensive rats eyes and in the IOP-elevated rat eyes (n = 3/group, in the Morrison model of glaucoma), or Ad5TGFβ2-induced ocular hypertensive (OHT) mouse eyes (n = 5/group). IOP was measured at various time points up to 72 h, and the experiment was repeated in triplicate. Mouse aqueous humor outflow facility was determined with multiple flow-rate infusion and episcleral venous pressure estimated with manometry., Results: SA-2 upregulated cGMP levels (six- to ten-fold) with an half maximal effective concentration (EC 50 ) of 20.3 µM in the hTM cells and simultaneously upregulated (40-fold) the SOD enzyme when compared with the vehicle-treated hTM cells. SA-2 also protected hTM cells from TBHP-induced decrease in cell survival with an EC 50 of 0.38 µM. A single dose of slow-release SA-2 NPs (1% w/v) delivered as an eye drop significantly lowered IOP (by 30%) in normotensive and OHT rodent eyes after 3 h post-dose, with the effect lasting up to 72 h. A statistically significant increase in aqueous outflow facility and a decrease in episcleral venous pressure was observed in rodents at this dose at 54 h., Conclusions: Hybrid compound SA-2 upregulated cGMP in hTM cells, increased outflow facility and decreased IOP in rodent models of OHT. Compound SA-2 possessing an antioxidant moiety provided additive cytoprotective activity to oxidatively stressed hTM cells by scavenging reactive oxygen species (ROS) and increasing SOD enzyme activity. Additionally, the PLGA nanosuspension formulation (SA-2 NPs) provided longer duration of IOP-lowering activity (up to 3 days) in comparison with the free non-encapsulated SA-2 drug. The data have implications for developing novel, non-prostaglandin therapeutics for IOP-lowering and cytoprotective effects with the possibility of an eye drop dosing regimen of once every 3 days for patients with glaucoma., (Copyright © 2021 Molecular Vision.)

Liver stiffness is a reliable non-invasive predictor of Hepatic Venous Pressure Gradient (HVPG) above 10 mm Hg. However, it failed to predict higher thresholds of HVPG. Our aim was to investigate whether liver stiffness and selected previously published non-invasive blood biomarkers could predict higher HVPG thresholds in liver transplant candidates without ongoing alcohol use. One hundred and nine liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG measurement, liver stiffness measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France) and assessment of blood HVPG biomarkers (osteopontin, VCAM-1, IL-6, TNF-α, IL-1ra/IL-1F3 and ELF score). The correlation between liver stiffness and HVPG was linear up to 30 mm Hg of HVPG (r = 0.765, p < 0.0001). The regression lines had similar slopes for HVPG values below and above 16 mm Hg (p > 0.05) and the correlation in patients with HVPG <16 mm Hg (r = 0.456, p = 0.01) was similar to patients with HVPG ≥ 16 mm Hg (r = 0.499, p < 0.0001). The correlation was similar in the subgroup patients with alcoholic (r = 0.718, p < 0.0001), NASH (r = 0.740, p = 0.008), cryptogenic (r = 0.648, p = 0,0377), cholestatic and autoimmune (r = 0.706, p < 0.0001) and viral cirrhosis (r = 0.756, p < 0.0001). Liver stiffness distinguished patients with HVPG above 16, and 20 mm Hg with AUROCs 0.90243, and 0.86824, sensitivity 0.7656, and 0.7027, and specificity 0.9333, and 0.8750. All studied blood biomarkers correlated better with liver stiffness than with HVPG and their AUROCs did not exceed 0.8 at both HVPG thresholds. Therefore, a composite predictor superior to liver stiffness could not be established. We conclude that liver stiffness is a clinically reliable predictor of higher HVPG thresholds in non-drinking subjects with advanced liver cirrhosis., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To investigate changes in aqueous humor dynamics during intraocular pressure (IOP) elevation induced by circumlimbal suture in mice., Methods: Ocular hypertension (OHT) was induced by applying a circumlimbal suture behind the limbus in male adult C57BL6/J mice. In the OHT group, the suture was left in place for an average of 8 weeks (n = 10, OHT group). In the sham control group the suture was cut at 2 days (n = 9, sham group) and in the naïve control group (n = 5) no suture was implanted. IOP was measured at baseline across 3 days, 1 h post-suture implantation, and at the chronic endpoint. Anterior segments were assessed using optical coherence tomography (OCT). Episcleral venous pressure (EVP), total outflow facility (C), uveoscleral outflow (Fu) and aqueous humor flow rate (Fin) were determined using a constant-flow infusion model., Results: All aqueous dynamic and chronic IOP outcome measures showed no difference between sham and naïve controls (p > 0.05) and thus these groups were combined into a single control group. IOP was elevated in OHT group compared with controls (p < 0.01). Chronic suture implantation did not change pupil size, anterior chamber depth or iridocorneal angles (p > 0.05). EVP was significantly higher in OHT eyes compared to control eyes (p < 0.01). There was no statistical difference in C, Fu and Fin between groups (p > 0.05). A significant linear correlation was found between IOP and EVP (R 2  = 0.35, p = 0.001)., Conclusions: Circumlimbal suture implantation in mouse eyes results in chronic IOP elevation without angle closure. Chronic IOP elevation is likely to reflect higher EVP., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Peripheral venous pressure (PVP) monitoring is a noninvasive method to assess volume status. We investigated the correlation between PVP and central venous pressure (CVP) in heart failure (HF), heart transplant (HTx), and left ventricular assist device (LVAD) patients undergoing right heart catheterization (RHC). A prospective, cross-sectional study examining PVP in 100 patients from October 2018 to January 2020 was conducted. The analysis included patients undergoing RHC admitted for HF, post-HTx monitoring, or LVAD hemodynamic testing. Sixty percent of patients had HF, 30% were HTx patients, and 10% were LVAD patients. The mean PVP was 9.4 ± 5.3 mm Hg, and the mean CVP was 9.2 ± 5.8 mm Hg. The PVP and CVP were found to be highly correlated (r = 0.93, p < 0.00001). High correlation was also noted when broken down by HF (r = 0.93, p < 0.00001), HTx (r = 0.93, p < 0.00001), and LVAD groups (r = 0.94, p < 0.00005). In conclusion, there is a high degree of correlation between PVP and CVP in HF, HTx, and LVAD patients. PVP measurements can be used as a rapid, reliable, noninvasive estimate of volume status in these patient populations., Competing Interests: Conflicts of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Intravenous (IV) fluids are among the most common interventions performed in the emergency department. They are at times lifesaving, but if used recklessly can be harmful. Given their ubiquity, it is important to understand the history, physiology, and current strategies that govern the use of IV fluids during the resuscitation of the critically ill., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Abdominal aortic aneurysm (AAA) is associated with morphological and functional changes in both aneurysmal and non-aneurysmal arteries. However, it remains uncertain whether similar changes also exist in the venous vasculature. The aim of this study was to evaluate global venous function in patients with AAA and controls., Methods: This experimental study comprised 31 men with AAA (mean ± standard deviation age 70.0 ± 2.8 years) and 29 male controls (aged 70.6 ± 3.4 years). Venous occlusion plethysmography (VOP) was used to evaluate arm venous compliance at venous pressures between 10 and 60 mmHg in steps of 5 mmHg. Compensatory mobilisation of venous capacitance blood (capacitance response) was measured with a volumetric technique during experimental hypovolaemia induced by lower body negative pressure (LBNP)., Results: The VOP induced pressure-volume curve was significantly less steep in patients with AAA (interaction, p < .001), indicating lower venous compliance. Accordingly, the corresponding pressure-compliance curves displayed reduced venous compliance at lower venous pressures in patients with AAA vs. controls (interaction, p < .001; AAA vs. control, p = .018). After adjusting for arterial hypertension, diabetes mellitus, hyperlipidaemia, chronic obstructive pulmonary disease, and smoking, VOP detected differences in venous compliance remained significant at low venous pressures, that is, at 10 mmHg (p = .008), 15 mmHg (p = .013), and 20 mmHg (p = .026). Mean venous compliance was negatively correlated with aortic diameter (r = -.332, p = .010). Mobilisation of venous capacitance response during LBNP was reduced by approximately 25% in patients with AAA (p = .030), and the redistribution of venous blood during LBNP was negatively correlated with aortic diameter (r = -.417, p = .007)., Conclusion: Men with AAA demonstrated reduced venous compliance and, as a result, a lesser capacity to mobilise peripheral venous blood to the central circulation during hypovolaemic stress. These findings imply that the AAA disease may be accompanied by functional changes in the venous vascular wall., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background and Aims: A hepatic venous pressure gradient (HVPG) decrease of 20% or more (or ≤12 mm Hg) indicates a good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed to simplify the risk stratification after variceal bleeding using clinical data and HVPG., Methods: A total of 193 patients with cirrhosis (62% with ascites and/or hepatic encephalopathy [HE]) who were within 7 days of bleeding had their HVPG measured before and at 1-3 months of treatment with propranolol/nadolol plus endoscopic band ligation. The endpoints were rebleeding and rebleeding/transplantation-free survival for 4 years. Another cohort (n = 231) served as the validation set., Results: During follow-up, 45 patients had variceal bleeding and 61 died. The HVPG responders (n = 71) had lower rebleeding risk (10% vs. 34%, P = 0.001) and better survival than the 122 nonresponders (61% vs. 39%, P = 0.001). Patients with HE (n = 120) had lower survival than patients without HE (40% vs. 63%, P = 0.005). Among the patients with ascites/HE, those with baseline HVPG ≤ 16 mm Hg (n = 16) had a low rebleeding risk (13%). In contrast, among patients with ascites/HE and baseline HVPG > 16 mm Hg, only the HVPG responders (n = 32) had a good prognosis, with lower rebleeding risk and better survival than the nonresponders (n = 72) (respective proportions: 7% vs. 39%, P = 0.018; 56% vs. 30% P = 0.010). These findings allowed us to develop a strategy for risk stratification in which HVPG response was measured only in patients with ascites and/or HE and baseline HVPG > 16 mm Hg. This method reduced the "gray zone" (i.e., high-risk patients who had not died on follow-up) from 46% to 35% and decreased the HVPG measurements required by 42%. The validation cohort confirmed these results., Conclusions: Restricting HVPG measurements to patients with ascites/HE and measuring HVPG response only if the patient's baseline HVPG is over 16 mm Hg improves detection of high-risk patients while markedly reducing the number of HVPG measurements required., (© 2020 by the American Association for the Study of Liver Diseases.)

Introduction: Little is known about how changes in physiologic parameters affect venous sinus pressure measurements, waveforms, or gradients associated with sinus stenosis., Objective: To evaluate the effect of changes in cardiovascular and respiratory physiologic parameters on venous sinus pressure and caliber measurements in patients with idiopathic intracranial hypertension (IIH) undergoing venous sinus stenting., Methods: In a prospective, randomized pilot study, eight patients with IIH undergoing venous sinus stenting were randomized to one of two groups. Under general anesthesia, patients underwent venous manometry and waveform recordings twice in succession based on assigned physiologic groups immediately before stenting. The mean arterial pressure (MAP) group maintained normocapnia but modified MAPs in two arms to control for temporal confounding: group A1 (MAP 60-80 mm Hg then 100-110 mm Hg) and group A2 (MAP 100-110 mm Hg then 60-80 mm Hg). The end-tidal carbon dioxide (EtCO 2 ) group maintained a high-normal MAP similar to standard neuroanesthesia goals and modified EtCO 2 : group B1 (EtCO 2 24-26 mm Hg then 38-40 mm Hg) and B2 (EtCO 2 28-40 mm Hg then 24-26 mm Hg)., Results: In group A, superior sagittal sinus (SSS) pressures (ranging from 8 to 76 mm Hg) and trans-stenotic pressure gradients (TSPGs) (ranging from 2 to 67 mm Hg) were seen at MAP of 100-110 mm Hg compared with SSS pressures (4-38 mm Hg) and TSPGs (3-31 mm Hg) at 60-80 mm Hg. In group B, SSS pressures and TSPGs were considerably higher at EtCO 2 levels of 38-40 mm Hg (15-57 mm Hg and 3-44 mm Hg, respectively) than at 24-26 mm Hg (8-26 mm Hg and 1-8 mm Hg, respectively)., Conclusions: Despite the small sample size, this pilot study demonstrates a dramatic effect of both MAP and EtCO 2 on venous sinus pressures obtained during venography. These findings underscore the importance of maintaining normal physiologic cardiovascular and respiratory parameters during venous sinus manometry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced chronic liver disease followed by an instruction for transjugular biopsy. Under local anesthesia and ultrasound guidance, a catheter introducer sheath is placed in the right internal jugular vein. Using fluoroscopic guidance, a balloon catheter is advanced into the inferior vena cava (IVC) and inserted into a large hepatic vein. Correct and sufficient wedge position of the catheter is ensured by injecting contrast media while the balloon is blocking the outflow of the cannulated hepatic vein. After calibrating the external pressure transducer, continuous pressure recordings are obtained with triplicate recordings of the wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP). The difference between FHVP and WHVP is referred to as HVPG, with values ≥10 mm Hg indicating clinically significant portal hypertension (CSPH). Before removing the catheter, pressure readings obtained in the IVC at the same level, as well as the right atrial pressure are recorded. Finally, a transjugular liver biopsy can be obtained via the same vascular route. Different systems are available; however, core biopsy needles are preferred over aspiration needles, especially for cirrhotic livers. Again, under fluoroscopic guidance a biopsy needle introducer sheath is advanced into an hepatic vein. Next, the transjugular biopsy needle is gently advanced through the introducer sheath: (i) in case of aspiration biopsy, the needle is advanced into the liver parenchyma under aspiration and then removed quickly, or (ii) in case of a core biopsy, the cutting-mechanism is triggered inside the parenchyma. Several separate passages can be safely performed to obtain sufficient liver specimens via transjugular biopsy. In experienced hands, the combination of these procedures takes about 30-45 min.

Introduction: Beta-blockers are the mainstay agents for portal pressure reduction and to modestly reduce hepatic venous pressure gradient (HVPG). We studied whether addition of simvastatin to carvedilol in cirrhotic patients for primary prophylaxis improves the hemodynamic response., Methods: Cirrhotic patients with esophageal varices and with baseline HVPG > 12 mm Hg were prospectively randomized for primary prophylaxis to receive either carvedilol (group A, n = 110) or carvedilol plus simvastatin (group B, n = 110). Primary objective was to compare hemodynamic response (HVPG reduction of ≥20% or <12 mm Hg) at 3 months, and secondary objectives were to compare first bleed episodes, death, and adverse events., Results: The groups were comparable at baseline. The proportion of patients achieving HVPG response at 3 months was comparable between groups (group A-36/62 [58.1%], group B-36/59 [61%], P = 0.85). The degree of mean HVPG reduction (17.3% and 17.8%, respectively, P = 0.98) and hemodynamic response (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.43-1.83, P = 0.74) was also not different between the groups. Patients who achieved target heart rate with no hypotensive episodes in either group showed better hemodynamic response (77.8% vs 59.2%, P = 0.04). Failure to achieve target heart rate (OR: 0.48; 95% CI: 0.22-1.06) and Child C cirrhosis (OR: 4.49; 95% CI: 1.20-16.8) predicted nonresponse. Three (3.7%) patients on simvastatin developed transient transaminitis and elevated creatine phosphokinase and improved with drug withdrawal. Two patients in each group bled (P = 0.99). Three patients and 1 patient, respectively, in group A and B died (P = 0.32), with sepsis being the cause of death., Discussion: Addition of simvastatin to carvedilol for 3 months for primary prophylaxis of variceal bleeding does not improve hemodynamic response over carvedilol monotherapy. Simvastatin usage should be closely monitored for adverse effects in Child C cirrhotic patients.

Venous needle dislodgement (VND) during dialysis is a rarely occurring adverse event, which becomes life-threatening if not handled promptly. Because the standard venous pressure alarm, implemented in most dialysis machines, has low sensitivity, a novel approach using extracted cardiac information to detect needle dislodgement is proposed. Four features are extracted from the arterial and venous pressure signals of the dialysis machine, characterizing the mean venous pressure, the venous cardiac pulse pressure, the time delay, and the correlation between the two pressure signals. The features serve as input to a support vector machine (SVM), which determines whether dislodgement has occurred. The SVM is first trained on a set of laboratory data, and then tested on another set of laboratory data as well as on a small data set from clinical hemodialysis sessions. The results show that dislodgement can be detected after 12-17 s, corresponding to 24-143 ml blood loss. The standard venous pressure alarm used in clinical routine only detects 50% of the VNDs, whereas the novel method detects all VNDs and has a false alarm rate of 0.12 per hour, provided that the amplitude of the extracted cardiac pressure signal exceeds 1 mmHg. The results are promising; however, the method needs to be tested on a larger set of clinical data to better establish its performance.

Background and Aims: Sustained virologic response (SVR) to interferon (IFN)-free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN-free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH., Approach and Results: The study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline [BL]) and after (follow-up [FU]) IFN-free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08-1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninvasive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve [AUROC],  < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86-0.92) in most patients, especially if assessed in a sequential manner., Conclusions: Reassessment of HVPG after SVR improved prognostication in patients with pretreatment CSPH. An "immediate" HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for interventions that lower portal pressure by decreasing intrahepatic resistance., (© 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.)

Objective: To determine the relationship between normal physiologic and pathologic venous sinus pressures in patients with idiopathic intracranial hypertension (IIH), which is poorly understood., Methods: Retrospective analysis was performed to identify patients with medically refractory IIH who were evaluated by angiography and retrograde venography with venous manometry. Patients were further subdivided into groups based on anatomic factors., Results: 104 patients met inclusion criteria for the study. In the absence of non-invasive venographic screening, 58% of patients in this series were found to have pressure gradients of ≥8 mm Hg; 93% were located near the transverse-sigmoid sinus junction. Opening pressure (OP) is strongly predictive of superior sagittal sinus (SSS) pressures (p<0.001) and also of the presence of a pressure gradient ≥8 mm Hg (p<0.001). Twenty-three percent of patients with an OP <25 had a pressure gradient ≥8 mm Hg compared with 77% of patients with an OP ≥35. Analysis of patients with OP ≤20 suggests that SSS pressures in patients without IIH should be less than 16-18 mm Hg with total cranial gradients <5 mm Hg. Across all patients, a pressure decrement of approximately 1 mm Hg occurs with progressively more caudal transition across anatomic points of measurement., Conclusions: This study describes intracranial and extracranial venous pressure measurements and gradients in different subgroups of patients with IIH. OP is highly predictive of intracranial venous pressures and significant venous pressure gradients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Glaucoma is a major cause of blindness, and IOP reduction remains the only clinically-validated therapy. In this study, we analyze a novel IOP-lowering strategy that uses a modest negative pressure (vacuum) applied locally to the periorbital region by a pair of goggles with each lens individually connected to a programmable pump. Motivated by clinical data showing an IOP reduction, we used an existing validated lumped-parameter model of the eye to understand the putative mechanism of this treatment. The model considers aqueous humor dynamics, episcleral venous pressure, and changes in ocular blood volume to describe how IOP changes with time in response to an external perturbation. We find that clinical data are qualitatively and quantitatively consistent with model predictions if we include two primary mechanisms in the model: first, negative pressure application causes a relatively rapid increase in globe volume accompanied by increased blood volume in the eye. Second, negative pressure application reduces episcleral venous pressure, causing a slower adjustment of IOP due to altered aqueous humor dynamics. These results provide testable hypotheses that hopefully will lead to a fuller experimentally-driven understanding of how negative periocular pressure influences IOP. Evaluating the long-term effects of such treatments on glaucoma patients requires further clinical study., Competing Interests: Declaration of competing interest We disclose the following: Ross Ethier is a consultant to Equinox Ophthalmic, Inc., the developer of the goggle system. Paul Yoo is an employee of Equinox Ophthalmic, Inc. John P. Berdahl is the founder and CEO of Equinox Ophthalmic, Inc. and holds patents licensed to Equinox Ophthalmic, Inc., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Portal hypertension (PH) is a severe disease with a poor outcome. Hepatic venous pressure gradient (HVPG), the current gold standard to detect PH, is available only in few hospitals due to its invasiveness and technical difficulty. This study aimed to establish and assess a novel model to calculate HVPG based on biofluid mechanics., Methods and Analysis: This is a prospective, randomised, non-controlled, multicentre trial. A total of 248 patients will be recruited in this study, and each patient will undergo CT, blood tests, Doppler ultrasound and HVPG measurement. The study consists of two independent and consecutive cohorts: original cohort (124 patients) and validation cohort (124 patients). The researchers will establish and improve the HVPG using biofluid mechanics (HVPG BFM )model in the original cohort and assess the model in the validation cohort., Ethics and Dissemination: The study was approved by the Scientific Research Projects Approval Determination of Independent Ethics Committee of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (approval number 2017-430 T326). Study findings will be disseminated through peer-reviewed publications and conference presentations., Trial Registration Number: NCT03470389., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

PRéCIS:: A positive correlation was observed between intraocular pressure (IOP) and central venous pressure (CVP) in patients with single ventricle (SV) during the perioperative period. IOP needs to be carefully monitored in the postoperative period after the Glenn and Fontan procedures, particularly the Glenn procedure., Purpose: SV is a cardiac malformation characterized by the existence of only 1 functional ventricle and is treated using the Glenn and Fontan procedures. Significant changes occur in CVP after these procedures. IOP has been reported to differ in the same individual when measured in a seated or supine position, which may be related to CVP. In the present study, we examined the relationship between CVP and IOP before and after surgery for SV., Patients and Methods: This study was a prospective, nonrandomized case series. All patients had SV and this study excluded those with eye diseases associated with ocular hypertension. We measured IOP before and after the Glenn or Fontan procedure. CVP was concurrently monitored., Results: Twenty-eight eyes of 14 patients with SV who underwent the Glenn (N=8) or Fontan (N=6) procedure were examined. Mean ages (±SD) were 2.6±0.7 months for the Glenn procedure and 24.0±2.7 months for the Fontan procedure. A correlation was observed between CVP and IOP in the perioperative period. IOP and CVP were both significantly higher after than before the Glenn and/or Fontan procedures. However, no relationship was noted between changes in IOP and CVP after the Glenn and/or Fontan procedures., Conclusions: Elevations in CVP significantly increased IOP in patients with SV who underwent the Glenn or Fontan procedure. IOP needs to be carefully monitored in the postoperative period after both procedures.

Objective Therapeutic predictors derived from the venous pressure before therapy have not been identified for Budd-Chiari syndrome (BCS). The aim of this study was to determine whether or not measuring the distal pressure or pressure gradient was useful for predicting treatment efficacy in BCS. Methods We retrospectively analyzed seven consecutive patients diagnosed with symptomatic BCS at our hospital between 2008 and 2017. Distal and proximal venous pressures at occlusion sites of BCS were measured before treatment in all cases. The pressure gradient was defined as the difference between distal and proximal venous pressures. A receiver operating characteristics (ROC) analysis was performed for venous pressures. Results Percutaneous old balloon angioplasty (POBA) was performed in seven cases, with technical success achieved in all cases (100%). No complications were encountered. The median primary patency was 574 (interquartile range, 439.5-1,056.5) days. The 1-year primary patency rate was 71.73%. Six cases (85.7%) showed resolution of symptoms, representing clinical success. The ROC analysis revealed a high distal pressure (area under the ROC curve = 0.83, cut-off=12 mmHg) as a predictor of treatment efficacy of POBA for symptomatic BCS. In addition, the pressure gradient was considered significant from a clinical perspective, because the 6 successful cases with resolution of symptoms showed a large pressure gradient (range, 8-21 mmHg) before treatment, whereas the failed case showed a relatively small pressure gradient (7 mmHg). Conclusion High distal pressure and a large pressure gradient might predict the treatment efficacy of balloon angioplasty for symptomatic BCS.

An understanding of the complexity of the cardiovascular system is incomplete without a knowledge of the venous system. It is important for students to understand that, in a closed system, like the circulatory system, changes to the venous side of the circulation have a knock-on effect on heart function and the arterial system and vice versa. Veins are capacitance vessels feeding blood to the right side of the heart. Changes in venous compliance have large effects on the volume of blood entering the heart and hence cardiac output by the Frank-Starling Law. In healthy steady-state conditions, venous return has to equal cardiac output, i.e., the heart cannot pump more blood than is delivered to it. A sound understanding of the venous system is essential in understanding how changes in cardiac output occur with changes in right atrial pressure or central venous pressure, and the effect these changes have on arterial blood pressure regulation. The aim of this paper is to detail simple hands-on physiological assessments that can be easily undertaken in the practical laboratory setting and that illustrate some key functions of veins. Specifically, we illustrate that venous valves prevent the backflow of blood, that venous blood pressure increases from the heart to the feet, that the skeletal muscle pump facilitates venous return, and we investigate the physiological and clinical significance of central venous pressure and how it may be assessed.

Objective: Identifying fluid responsiveness is critical to optimizing perfusion while preventing fluid overload. An experimental study of hypovolemic shock resuscitation showed the importance of ventricular compliance and peripheral venous pressure (PVP) on fluid responsiveness. The authors tested the hypothesis that reduced ventricular compliance measured using transesophageal echocardiography results in decreased fluid responsiveness after a fluid bolus., Design: Prospective observational study., Setting: Two-center, university hospital study., Participants: The study comprised 29 patients undergoing elective coronary revascularization., Intervention: Albumin 5%, 7 mL/kg, was infused over 10 minutes to characterize fluid responders (>15% increase in stroke volume) from nonresponders., Measurements and Main Results: Invasive hemodynamics and the ratio of mitral inflow velocity (E-wave)/annular relaxation (e'), or E/e' ratio, were measured using transesophageal echocardiography to assess left ventricular (LV) compliance at baseline and after albumin infusion. Fifteen patients were classified as responders and 14 as nonresponders. The E/e' ratio in responders was 7.4 ± 1.9 at baseline and 7.1 ± 1.8 after bolus. In contrast, E/e' was significantly higher in nonresponders at baseline (10.7 ± 4.6; p = 0.04) and further increased after bolus (12.6 ± 5.5; p = 0.002). PVP was significantly greater in the nonresponders at baseline (14 ± 4 mmHg v 11 ± 3 mmHg; p = 0.02) and increased in both groups after albumin infusion. Fluid responsiveness was tested using the area under the receiver operating characteristic curve and was 0.74 for the E/e' ratio (95% confidence interval 0.55-0.93; p = 0.029) and 0.72 for the PVP (95% confidence interval 0.52-0.92; p = 0.058)., Conclusion: Fluid responders had normal LV compliance and lower PVP at baseline. In contrast, nonresponders had reduced LV compliance, which worsened after fluid bolus. E/e,' more than PVP, may be a useful clinical index to predict fluid responsiveness., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Episcleral venous pressure (EVP) greatly influences steady-state IOP and recent evidence suggests a neuronal influence on EVP. Yet little is known about the innervation of the episcleral circulation and, more specifically, the neurotransmitters involved. We identify possible neurotransmitter candidates in the episcleral circulation of rats., Methods: Eight immersion-fixated rat eyes taken from four animals were cut into serial sections, followed by standard immunohistochemistry. Antibodies against choline acetyltransferase, dopamine-β-hydroxylase, synaptophysine, PGP 9.5, VIP, neuronal nitric oxide synthase (nNOS), substance P, CGRP, and galanin were used. Additionally, colocalization experiments with smooth muscle actin and neurofilament (200 kDa) were performed., Results: In all specimens, the episcleral vessels showed immunoreactivity for smooth muscle actin and were reached by neurofilament (200 kDa)-positive structures. Furthermore, these structures colocalized with immunoreactivity for PGP 9.5, synaptophysine, choline acetyl transferase (ChAT), dopamine-β-hydroxylase, VIP, CGRP, nNOS, substance P and galanin., Conclusions: These findings indicate that there is neuronal input to the episcleral circulation. ChAT and VIP as well as dopamine-β-hydroxylase suggest parasympathetic and sympathetic innervation. Further studies are needed on whether the positively-stained structures are of functional significance for the regulation of the episcleral venous pressure and thereby IOP.

Objectives: Spleen stiffness (SS) correlates with liver stiffness (LS) and hepatic venous pressure gradient. The latter is currently the most accurate predictor of hepatic decompensation. Our study aims to check whether SS has a similar predictive capability, while being an easy-to-perform noninvasive test in a real-life patient cohort., Methods: Concomitantly, 210 successive patients were examined and received liver and SS measurements and a standard laboratory. Patients were observed for 1 year in terms of clinical signs of decompensation., Results: One hundred fifty-nine of the initial 210 patients had a valid LS and SS measurement and were evaluable for clinical follow-up. Twelve patients developed a hepatic decompensation; with a SS >39 kPa (P=0.0005). Especially in a group with elevated LS, patients with a high risk of decompensation could be identified using SS. Patients with comparable LS who suffered from acute liver damage had significantly lower SS than respective patients with chronic liver damage (30.97 vs. 46.03 kPa; P=0.04). Acute liver failure was associated with elevated LS (16.47 kPa) but not with elevated SS (30.97 kPa)., Conclusions: The risk of a hepatic decompensation can easily be assessed using SS measurement. Therefore SS measurement might be a powerful screening tool identifying patients who need closer monitoring. Moreover, SS is able to differentiate between acute and chronic or acute on chronic liver damage.

Background: No standard dehydration monitor exists for children. This study attempts to determine the utility of Fast Fourier Transform (FFT) of a peripheral venous pressure (PVP) waveform to predict dehydration., Materials and Methods: PVP waveforms were collected from 18 patients. Groups were defined as resuscitated (serum chloride ≥ 100 mmol/L) and hypovolemic (serum chloride < 100 mmol/L). Data were collected on emergency department admission and after a 20 cc/kg fluid bolus. The MATLAB (MathWorks) software analyzed nonoverlapping 10-s window signals; 2.4 Hz (144 bps) was the most demonstrative frequency to compare the PVP signal power (mmHg)., Results: Admission FFTs were compared between 10 (56%) resuscitated and 8 (44%) hypovolemic patients. The PVP signal power was higher in resuscitated patients (median 0.174 mmHg, IQR: 0.079-0.374 mmHg) than in hypovolemic patients (median 0.026 mmHg, IQR: 0.001-0.057 mmHg), (P < 0.001). Fourteen patients received a bolus regardless of laboratory values: 6 (43%) resuscitated and 8 (57%) hypovolemic. In resuscitated patients, the signal power did not change significantly after the fluid bolus (median 0.142 mmHg, IQR: 0.032-0.383 mmHg) (P = 0.019), whereas significantly increased signal power (median 0.0474 mmHg, IQR: 0.019-0.110 mmHg) was observed in the hypovolemic patients after a fluid bolus at 2.4 Hz (P < 0.001). The algorithm predicted dehydration for window-level analysis (sensitivity 97.95%, specificity 93.07%). The algorithm predicted dehydration for patient-level analysis (sensitivity 100%, specificity 100%)., Conclusions: FFT of PVP waveforms can predict dehydration in hypertrophic pyloric stenosis. Further work is needed to determine the utility of PVP analysis to guide fluid resuscitation status in other pediatric populations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Objective: Parameters of mathematical models of the cardiovascular system can be used to monitor cardiovascular state, such as total stressed blood volume status, vessel elastance and resistance. To do so, the model parameters have to be estimated from data collected at the patient's bedside. This work considers a seven-parameter model of the cardiovascular system and investigates whether these parameters can be uniquely determined using indices derived from measurements of arterial and venous pressures, and stroke volume., Methods: An error vector defined the residuals between the simulated and reference values of the seven clinically available haemodynamic indices. The sensitivity of this error vector to each model parameter was analysed, as well as the collinearity between parameters. To assess practical identifiability of the model parameters, profile-likelihood curves were constructed for each parameter., Results: Four of the seven model parameters were found to be practically identifiable from the selected data. The remaining three parameters were practically non-identifiable. Among these non-identifiable parameters, one could be decreased as much as possible. The other two non-identifiable parameters were inversely correlated, which prevented their precise estimation., Conclusions: This work presented the practical identifiability analysis of a seven-parameter cardiovascular system model, from limited clinical data. The analysis showed that three of the seven parameters were practically non-identifiable, thus limiting the use of the model as a monitoring tool. Slight changes in the time-varying function modeling cardiac contraction and use of larger values for the reference range of venous pressure made the model fully practically identifiable., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Vital signs are included in the determination of shock secondary to hemorrhage; however, more granular predictors are needed. We hypothesized that fast Fourier transformation (FFT) would have a greater percent change after hemorrhage than heart rate (HR) or systolic blood pressure (SBP). Using a porcine model, nine 17 kg pigs were hemorrhaged 10% of their calculated blood volume. Peripheral venous pressure waveforms, HR and SBP were collected at baseline and after 10% blood loss. FFT was performed on the peripheral venous pressure waveforms and the peak between 1 and 3 hertz (f1) corresponded to HR. To normalize values for comparison, percent change was calculated for f1, SBP, and HR. The mean percent change for f1 was an 18.8% decrease; SBP was a 3.31% decrease; and HR was a 0.95% increase. Using analysis of variance, FFT at f1 demonstrates a statistically significant greater change than HR or SBP after loss of 10% of circulating blood volume (p = 0.0023). Further work is needed to determine if this could be used in field triage to guide resuscitation., (© The Author 2019. Published by Oxford University Press [on behalf of Association of Military Surgeons of the United States].)

The Fontan procedure provides relief from cyanosis in patients with univentricular hearts. A major clinical unmet need is to understand whether the venous flow patterns of the Fontan circulation lead to the development of congestive hepatopathy and other life-threatening complications. Currently, there is no consensus on whether heart beat or respiration is the main driving force of venous return and which one affects the periodic flow changes for the most (i. e., pulsatility). The present study, for the first time, quantified respiratory and cardiac components of the venous flow in the inferior vena cava (IVC) of 14 Fontan patients and 11 normal controls using a novel approach ("physio-matrix"). We found that in contrast to the normal controls, respiration in Fontan patients had a significant effect on venous flow pulsatility, and the ratio of respiration-dependent to the cardiac-dependent pulsatility was positively associated with the retrograde flow. Nevertheless, the main driving force of net IVC flow was the heart beat and not respiration. The separate analysis of the effects of respiration and heart beat provides new insights into the abnormal venous return patterns that may be responsible for adverse effects on liver and bowel of the patients with Fontan circulation.

Aims: We report the cerebrospinal fluid opening pressure (CSF-OP) measurements obtained before and after venous sinus stenting (VSS) in 50 patients with idiopathic intracranial hypertension., Methods: The CSF-OP was measured with a spinal tap 3 months before and 3 months after treatment. All data were prospectively collected and included patient demographics, weight (kg), body mass index (BMI), acetazolamide daily dosage (mg), procedural details, complications, venous sinus pressures (mm Hg), trans-stenotic pressure gradient (mm Hg), transverse sinus symmetry, and type of venous sinus stenosis., Results: The average pretreatment CSF-OP was 37 cm H 2 O (range 25-77) and the average post-treatment CSF-OP was 20.2 cm H 2 O (range 10-36), with an average reduction of 16.8 cm H 2 O (P<0.01). The post-treatment CSF-OP was less than 25 cm H 2 O in 40/50 patients. The average acetazolamide daily dose decreased from 950 mg to 300 mg at the time of 3-month follow-up (P<0.01). No patient required an increase in acetazolamide dose 3 months after VSS. The average weight before treatment was 95.4 kg with an average BMI of 35.41. There was an average increase in body weight of 1.1 kg at the 3-month follow-up with an average increase in BMI of 0.35 (P=0.03)., Conclusions: We provide evidence that there is a significant decrease in CSF-OP in patients with idiopathic intracranial hypertension 3 months after VSS, independent of acetazolamide usage or weight loss., Competing Interests: Competing interests: Dr Gobin is the founder, medical director and CEO of Serenity Medical None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In the diagnosis of venous stenosis associated with idiopathic intracranial hypertension, previous studies have identified significant differences when venous pressures are measured under conscious sedation versus general anesthesia. No previous reports have investigated the effect that respiratory parameters may have on cerebral venous sinus pressure and the associated trans-stenosis pressure gradient., Case Description: Two patients with idiopathic intracranial hypertension were retrospectively identified from a prospective database wherein venous manometry was performed as part of a venous stenting procedure with waveform recording during changes in end-tidal carbon dioxide level (EtCO 2 ). Upon microcatheterization of the superior sagittal sinus after induction of general anesthesia, both patients were noted to have an EtCO 2 of 29 mm Hg. After EtCO 2 was corrected to 40 mm Hg, repeat venous manometry was conducted, which demonstrated increased SSS venous pressures from 12.6 to 21.1 mm Hg and 18.4 to 30.3 mm Hg in patients 1 and 2, respectively. In addition, the waveform amplitude increased in both patients after EtCO 2 correction., Conclusions: This series demonstrates that EtCO 2 changes have an immediate and pronounced effect on venous sinus pressure measurements with waveform changes that may correlate to increased intracranial pressure. These findings underscore the need to perform measurements of venous sinus pressure gradients under normal awake conditions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Idiopathic elevated episcleral venous pressure (IEEVP) or idiopathic dilated episcleral veins (IDEV) is a rare abnormality, and thus therapeutic treatment for this condition rarely is discussed. We report a case of a patient with bilateral glaucoma secondary to IDEV for whom intraocular pressures (IOPs) were controlled successfully by trabeculectomy., Case Presentation: A 50 year-old female with a complaint of persistent red eyes for over 30 years, presented with numerous tortuous and engorged episcleral vessels in both eyes (OU), open angles OU with spontaneous blood in Schlemm's canal 360 degrees bilaterally. Orbital color Doppler examination showed the superior ophthalmic veins to be of normal calibre, with no reversal of flow. Head MRI with contrast and cerebral angiography were negative for arteriovenous fistula. Coronary angiography, color Doppler echocardiography and chest radiographs were within normal limits. A diagnosis of secondary glaucoma and IDEV was made. Neither anti-glaucoma medications, nor laser trabeculoplasty reduced the patent's IOP effectively. Only after trabeculectomy was performed in each eye, were IOPs successfully controlled., Conclusions: This case serves to remind clinicians of the importance of identifying and evaluating thoroughly patients with episcleral vessel dilation in non-inflamed eyes with no known cause. A misdiagnosis or missed diagnosis of long-term elevated intraocular pressure may result in significant damage to the optic nerve. In addition, when performing filtration surgery it is crucial that the ophthalmologist control the IOP and make an effort to prevent choroidal effusion.