Monitoring the venous circulation: novel techniques and applications.

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.

Measurement of the retinal venous pressure with a new instrument in healthy subjects.

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.

The Distribution of Retinal Venous Pressure and Intraocular Pressure Differs Significantly in Patients with Primary Open-Angle Glaucoma.

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), ß-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 ß-blocker group. Here, the 17 patients with systemic ß-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 ß-blocker. The median IOP was 15.7 mmHg with systemic ß-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 ß-blockers, in which the RVP was lower by 4.6 mmHg than for the patients who did not receive these drugs (p = 0.003).

Algebraic formulas characterizing an alternative to Guyton's graphical analysis relevant for heart failure.

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.

Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon-Free Therapy.

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.

A Prognostic Strategy Based on Stage of Cirrhosis and HVPG to Improve Risk Stratification After Variceal Bleeding.

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.

Nanoencapsulated hybrid compound SA-2 with long-lasting intraocular pressure-lowering activity in rodent eyes.

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 Ad5TGFß2-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 (EC50) 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 EC50 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.

Episcleral venous pressure response to brain stem stimulation: Effect of topical lidocaine.

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.

Increased episcleral venous pressure in a mouse model of circumlimbal suture induced ocular hypertension.

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 (R2 = 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.

Sinistral Portal Hypertension Prediction During Pancreatoduodenectomy With Splenic Vein Resection.

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.

Evaluation of umbilical venous flow volume measured using ultrasound compared to circuit flow volume in the EXTra-uterine Environment for Neonatal Development (EXTEND) system in fetal sheep.

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.

Hemodynamic Effects of Adding Simvastatin to Carvedilol for Primary Prophylaxis of Variceal Bleeding: A Randomized Controlled Trial.

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.

The effects of negative periocular pressure on intraocular pressure.

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.

Assessment of Upper Extremity Venous Compliance in Patients With Abdominal Aortic Aneurysms.

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.

Venous Physiology Predicts Dehydration in the Pediatric Population.

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.

Spleen Stiffness Differentiates Between Acute and Chronic Liver Damage and Predicts Hepatic Decompensation.

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.

Diastolic Function and Peripheral Venous Pressure as Indices for Fluid Responsiveness in Cardiac Surgical Patients.

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.

Understanding basic vein physiology and venous blood pressure through simple physical assessments.

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.

Hepatic transudation barrier properties.

OBJECTIVE: Fluid and protein continuously transude from the surface of the liver. Despite a common understanding that transudation plays a critical role in hepatic interstitial and peritoneal fluid balance, transudation from the entire liver has not been studied. Therefore, the goal of the present work was to provide the first direct measurement of the hepatic transudation rate and transudation barrier properties. METHODS: Transudation rates were determined by collecting transudate from the entire liver. Hydraulic conductivity, and fluid transudation and protein reflection coefficients of the transudation barrier (formed by the subscapular interstitial matrix, capsule, and peritoneum) were determined from changes in fluid and protein transudation rates in response to hepatic venous pressure elevation. RESULTS: Following hepatic venous pressure elevation from 6.1 ± 0.9 to 11.1 ± 0.6 mm Hg, transudation rate increased from 0.13 ± 0.03 to 0.37 ± 0.03 mL/min·100 g. Transudation barrier hydraulic conductivity, fluid transudation and protein reflection coefficients (3.9 × 10-4  ± 5.7 × 10-5  mL/min·mm Hg·cm2 , 0.36 ± 0.04 mL/min·mm Hg, and 0.09 ± 0.03, respectively) were comparable to those reported for hepatic sinusoids. CONCLUSIONS: Taken together, these findings suggest that the hepatic transudation barrier is highly permeable at elevated sinusoidal pressures. These fundamental studies provide a better understanding of the hepatic transudation barrier properties and transudation under conditions that are physiologically and clinically relevant to ascites formation.

Impact of right ventricular distensibility on congestive heart failure with preserved left ventricular ejection fraction in the elderly.

To elucidate involvement of age-related impairments of right ventricular (RV) distensibility in the elderly congestive heart failure (CHF), we examined the prevalence of less-distensible right ventricle in patients with preserved left ventricular ejection fraction (LVEF) over a wide range of ages. In 893 patients aged from 40 to 102 years, we simultaneously recorded electrocardiogram, phonocardiogram, and jugular venous pulse wave. Using signal-processing techniques, the prominent 'Y' descent of jugular pulse waveform was detected as a hemodynamic sign of a less-distensible right ventricle. Prevalence of less-distensible right ventricle and elevated RV systolic pressure increased along with aging from the 50s to the 90s in an exponential fashion from 3.3 and 12% up to 33 and 61%, respectively (p < 0.001 for each). This age-dependent deterioration of ventricular distensibility was not observed for the left ventricle. Higher age and higher RV systolic pressure were independently associated with less-distensible right ventricle (Odds ratio, 1.05 per 1 year, p = 0.003; and 1.03 per 1 mmHg, p = 0.026, respectively). The elderly CHF was associated with high prevalence of the less-distensible right ventricle and higher RV systolic pressure, both of which were independent risk factors for CHF (Odds ratio, 5.27, p = 0.001, and 1.08 per 1 mmHg, p < 0.001, respectively). In elderly patients with preserved LVEF, the combination of a less-distensible right ventricle and a high RV systolic pressure seems to be related to developing CHF. The less-distensible right ventricle and elevated RV systolic pressure are closely associated with CHF with preserved LVEF in the elderly patients.