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Strenuous physical training increases total blood volume (BV) through expansion of plasma volume (PV) and red cell volume (RCV). In contrast, exogenous erythropoietin (EPO) treatment increases RCV but decreases PV, rendering BV stable or slightly decreased. This study aimed to determine the combined effects of strenuous training and EPO treatment on BV and markers of systemic and muscle iron homeostasis. In this longitudinal study, eight healthy nonanemic males were treated with EPO (50 IU/kg body mass, three times per week, sc) across 28 days of strenuous training (4 days/wk, exercise energy expenditures of 1,334 ± 24 kcal/day) while consuming a controlled, energy-balanced diet providing 39 ± 4 mg/day iron. Before (PRE) and after (POST) intervention, BV compartments were measured using carbon monoxide rebreathing, and markers of iron homeostasis were assessed in blood and skeletal muscle (vastus lateralis). Training + EPO increased ( P < 0.01) RCV (13 ± 6%) and BV (5 ± 4%), whereas PV remained unchanged ( P = 0.86). The expansion of RCV was accompanied by a large decrease in whole body iron stores, as indicated by decreased ( P < 0.01) ferritin (-77 ± 10%) and hepcidin (-49 ± 23%) concentrations in plasma. Training + EPO decreased ( P < 0.01) muscle protein abundance of ferritin (-25 ± 20%) and increased ( P < 0.05) transferrin receptor (47 ± 56%). These novel findings illustrate that strenuous training combined with EPO results in both increased total oxygen-carrying capacity and hypervolemia in young healthy males. The decrease in plasma and muscle ferritin suggests that the marked upregulation of erythropoiesis alters systemic and tissue iron homeostasis, resulting in a decline in whole body and skeletal muscle iron stores. NEW & NOTEWORTHY Strenuous exercise training combined with erythropoietin (EPO) treatment increases blood volume, driven exclusively by red cell volume expansion. This hematological adaptation results in increased total oxygen-carrying capacity and hypervolemia. The marked upregulation of erythropoiesis with training + EPO reduces whole body iron stores and circulating hepcidin concentrations. The finding that the abundance of ferritin in muscle decreased after training + EPO suggests that muscle may release iron to support red blood cell production.

Dietary nitrate (NO 3 - ) supplementation is known to enhance nitric oxide (NO) activity and acts as a vasodilator. In this randomized crossover study, we investigated the effect of inorganic NO 3 - supplementation on the changes in calf venous volume during postural change and subsequent skeletal muscle pump activity. Fifteen healthy young adults were assigned to receive beetroot juice (BRJ) or a NO 3 - -depleted control beverage (prune juice: CON). Two hours after beverage consumption, the changes in the right calf volume during postural change from supine to upright and a subsequent right tiptoe maneuver were measured using venous occlusion plethysmography. The increase in calf volume from the supine to upright position (total venous volume [VV]) and the decrease in calf volume during the right tiptoe maneuver (venous ejection volume [Ve]) were calculated. Plasma NO 3 - concentration was higher in the BRJ group than in the CON group 2 h after beverage intake ( p < 0.05). However, VV and Ve did not differ between CON and BRJ. These results suggest that acute intake of BRJ may enhance NO activity via the NO 3 - → nitrite → NO pathway but does not change calf venous pooling due to a postural change or the calf venous return due to skeletal muscle pump activity in healthy young adults.

A safe induction method of general anaesthesia for paediatric moyamoya disease patients has not been fully established. We had the opportunity to administer general anaesthesia twice to a two-year-old girl diagnosed with moyamoya disease. We used different induction methods for general anaesthesia at each session, i.e. slow induction with sevoflurane and rapid induction with propofol, and were able to evaluate changes in her left regional cortical blood volume (rCBV) and oxygenation (rCBO) during both anaesthesia inductions using near-infrared spectroscopy (NIRS). The mean change value of total-Hb (rCBV) (mean ± SD; μmol/L) in the rapid induction was lower than that in the slow induction (-0.54 ± 1.43 vs. 1.82 ± 1.74). However, the TOI (rCBO) levels during both anaesthesia inductions were constantly higher than these respective baseline values (64% in the slow induction, 71% in the rapid induction), and these mean change values in each of the anaesthesia induction were about the same. The present results suggested that both the slow induction method with sevoflurane and the rapid induction method with propofol might be safe and effective for anaesthesia induction in paediatric patients with moyamoya disease., (© 2024. Oxygen Transport to Tissue International.)

Background: Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality worldwide. Tranexamic acid (TXA) is a useful drug for prevention of PPH and merits evaluation in Nigeria, where PPH is the leading cause of maternal death (25%) and severe maternal morbidity. This study evaluates the efficacy of TXA in reducing blood loss following vaginal delivery., Methods: This was a double-blind randomized placebo-controlled study on the efficacy and safety of intravenous TXA in reducing blood loss in women undergoing vaginal delivery in a tertiary hospital. Data analysis was conducted with IBM SPSS software (version 20, Chicago II, USA). P-value < 0.05 was considered statistically significant., Results: The mean estimated blood loss was lower in TXA compared with the placebo group. (174.87 ± 119.83 ml versus 341.07 ± 67.97 ml respectively; P < 0.0001). PPH (blood loss > 500 ml) was 5.13% in the study arm compared to the control arm 7.14%- risk ratio (RR) 0.71; 95% CI: 0.38-1.79, p = 0.5956]. Additional uterotonics was required more in the control group compared to the treatment group 14(16.67%) versus 3(3.85%), p-value= 0.007. There were no major complications noticed in the treatment group., Conclusion: This study demonstrated that intravenous administration of TXA reduced blood loss following vaginal delivery. It also reduced the need for additional uterotonics. However, blood loss greater than 500 was not significantly reduced., Trial Registration: This trial was registered retrospectively. Pan African Clinical Trial Registry: PACTR202010828881019 on 12/10/2020., (© 2022. The Author(s).)

Objectives: Several small studies indicate the sulphonamide component of the drug sulfasalazine lowers HbA 1c. We investigated reduction of HbA 1c following incident prescription of sulfasalazine and related aminosalicylates, lacking the sulphonamide group, in an observational cohort., Research Design and Methods: Individuals in the Scottish Care Information Diabetes Collaboration (SCI-Diabetes) with type 2 diabetes and incident prescription for an aminosalicylate drug (sulfasalazine, mesalazine, olsalazine or balsalazide) were identified. Baseline and 6-month HbA 1c were required for eligibility, to calculate HbA 1c response. To investigate association with haemolysis, change in components of full blood count was assessed. Paired t-tests compared difference in baseline and treatment HbA 1c measures and other clinical variables., Results: In all, 113 individuals treated with sulfasalazine and 103 with mesalazine (lacking the sulphonamide group) were eligible, with no eligible individuals treated with olsalazine or balsalazide. Baseline characteristics were similar. Mean (SD) HbA 1c reduction at 6 months was -9 ± 16 mmol/mol (-0.9 ± 1.4%) (p < 0.0001) in those taking sulfasalazine with no reduction in those taking mesalazine (2 ± 16 mmol/mol (0.2 ± 1.4%). Sulfasalazine but not mesalazine was associated with a mean (SD) increase in mean cell volume of 3.7 ± 5.6 fl (p < 0.0001) and decrease in red cell count of -0.2 ± 0.4 × 10 -12 /L (p < 0.0001)., Conclusions: In this observational, population-based study, sulfasalazine initiation was associated with a 6-month reduction in HbA 1c . This correlated with haematological changes suggesting haemolytic effects of sulfasalazine. Haemolysis is proposed to contribute to HbA 1c lowering through the sulphonamide pharmacophore. This suggests that HbA 1c is not a reliable measure of glycaemia in individuals prescribed sulfasalazine., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Insulin increases muscle microvascular perfusion and enhances tissue insulin and nutrient delivery. Our aim was to determine phenotypic traits that foretell human muscle microvascular insulin responses. Hyperinsulinemic euglycemic clamps were performed in 97 adult humans who were lean and healthy, had class 1 obesity without comorbidities, or controlled type 1 diabetes without complications. Insulin-mediated whole-body glucose disposal rates (M-value) and insulin-induced changes in muscle microvascular blood volume (ΔMBV) were determined. Univariate and multivariate analyses were conducted to examine bivariate and multivariate relationships between outcomes, ΔMBV and M-value, and predictor variables, body mass index (BMI), total body weight (WT), percent body fat (BF), lean body mass, blood pressure, maximum consumption of oxygen (VO 2 max), plasma LDL (LDL-C) and HDL cholesterol, triglycerides (TG), and fasting insulin (INS) levels. Among all factors, only M-value (r = 0.23, p = 0.02) and VO 2 max (r = 0.20, p = 0.047) correlated with ΔMBV. Conversely, INS (r = - 0.48, p ≤ 0.0001), BF (r = - 0.54, p ≤ 0.001), VO 2 max (r = 0.5, p ≤ 0.001), BMI (r = - 0.40, p < 0.001), WT (r = - 0.33, p = 0.001), LDL-C (r = - 0.26, p = 0.009), TG (r = - 0.25, p = 0.012) correlated with M-value. While both ΔMBV (p = 0.045) and TG (p = 0.03) provided significant predictive information about M-value in the multivariate regression model, only M-value was uniquely predictive of ΔMBV (p = 0.045). Thus, both M-value and VO 2 max correlated with ΔMBV but only M-value provided unique predictive information about ΔMBV. This suggests that metabolic and microvascular insulin responses are important predictors of one another, but most metabolic insulin resistance predictors do not predict microvascular insulin responses.

The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study demonstrated that dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), reduced heart failure hospitalization and cardiovascular death in patients with heart failure with reduced ejection fraction (HF-rEF), with and without type 2 diabetes mellitus. Multiple potential mechanisms have been proposed to explain this benefit, which may be multifactorial. This study aimed to quantify the contribution of the known natriuretic/diuretic effects of SGLT2is to changes in cardiac hemodynamics, remodeling, and fluid homeostasis in the setting of HF-rEF. An integrated cardiorenal mathematical model was used to simulate inhibition of SGLT2 and its consequences on cardiac hemodynamics in a virtual population of HF-rEF patients generated by varying model parameters over physiologically plausible ranges and matching to baseline characteristics of individual DAPA-HF trial patients. Cardiovascular responses to placebo and SGLT2i over time were then simulated. The baseline characteristics of the HF-rEF virtual population and DAPA-HF were in good agreement. SGLT2i-induced diuresis and natriuresis that reduced blood volume and interstitial fluid volume, relative to placebo within 14 days. This resulted in decreased left ventricular end-diastolic volume and pressure, indicating reduced cardiac preload. Thereafter, blood volume and interstitial fluid volume again began to accumulate, but pressures and volumes remained shifted lower relative to placebo. After 1 year, left ventricle mass was lower and ejection fraction was higher than placebo. These simulations considered only hemodynamic consequences of the natriuretic/diuretic effects of SGLT2i, as other mechanisms may contribute additional benefits besides those predictions., (© 2020, The American College of Clinical Pharmacology.)

Understanding cellular contributions to hemodynamic activity is essential for interpreting blood-based brain mapping signals. Optogenetic studies examining cell-specific influences on local hemodynamics have reported that excitatory activity results in cerebral perfusion and blood volume increase, while inhibitory activity contributes to both vasodilation and vasoconstriction. How specific subpopulations of interneurons regulate the brain's blood supply is less examined. Parvalbumin interneurons are the largest subpopulation of GABAergic neurons in the brain, critical for brain development, plasticity, and long-distance excitatory neurotransmission. Despite their essential role in brain function, the contribution of parvalbumin neurons to neurovascular coupling has been relatively unexamined. Using optical intrinsic signal imaging and laser speckle contrast imaging, we photostimulated awake and anesthetized transgenic mice expressing channelrhodopsin under a parvalbumin promoter. Increased parvalbumin activity reduced local oxygenation, cerebral blood volume, and cerebral blood flow. These "negative" hemodynamic responses were consistent within and across mice and reproducible across a broad range of photostimulus parameters. However, the sign and magnitude of the hemodynamic response resulting from increased parvalbumin activity depended on the type and level of anesthesia used. Opposed hemodynamic responses following increased excitation or parvalbumin-based inhibition suggest unique contributions from different cell populations to neurovascular coupling.

Background: Investigators have hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert diuretic effects that contribute to their ability to reduce serious heart failure events, and this action is particularly important in patients with fluid retention., Objectives: This study sought to evaluate the effects of the SGLT2 inhibitor empagliflozin on symptoms, health status, and major heart failure outcomes in patients with and without recent volume overload., Methods: This double-blind randomized trial compared the effects of empagliflozin and placebo in 3,730 patients with heart failure and a reduced ejection fraction, with or without diabetes. Approximately 40% of the patients had volume overload in the 4 weeks before study enrollment., Results: Patients with recent volume overload were more likely to have been hospitalized for heart failure and to have received an intravenous diuretic agent in an outpatient setting in the previous 12 months, and to experience a heart failure event following randomization, even though they were more likely to be treated with high doses of a loop diuretic agent as an outpatient (all p < 0.001). When compared with placebo, empagliflozin reduced the composite risk of cardiovascular death or hospitalization for heart failure, decreased total hospitalizations for heart failure, and improved health status and functional class. Yet despite the predisposition of patients with recent volume overload to fluid retention, the magnitude of these benefits (even after 1 month of treatment) was not more marked in patients with recent volume overload (interaction p values > 0.05). Changes in body weight, hematocrit, and natriuretic peptides (each potentially indicative of a diuretic action of SGLT2 inhibitors) did not track each other closely in their time course or in individual patients., Conclusions: Taken together, study findings do not support a dominant role of diuresis in mediating the physiological changes or clinical benefits of SGLT2 inhibitors on the course of heart failure in patients with a reduced ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)., Competing Interests: Funding Support and Author Disclosures The EMPEROR-Reduced trial was supported by Boehringer Ingelheim and Eli Lilly and Company. Dr. Packer has received personal fees from Boehringer Ingelheim during the conduct of the study; and has received personal fees from Abbvie, Akcea, Amarin, AstraZeneca, Amgen, Boehringer Ingelheim, Cardiorentis, Daiichi-Sankyo, Johnson & Johnson, Lilly, Novartis, Pfizer, Relypsa, Sanofi, Synthetic Biologics, Theravance, and NovoNordisk outside the submitted work. Dr. Anker has received grants and personal fees from Vifor Int. and Abbott Vascular; has received personal fees from AstraZeneca, Bayer, Brahms, Boehringer Ingelheim, Cardiac Dimensions, Novartis, Occlutech, Servier, and Vifor Int.; and has received personal fees from Boehringer Ingelheim during the conduct of the study. Dr. Butler has received consulting fees from Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd., and Vifor; and has received personal fees from Boehringer Ingelheim during the conduct of the study. Dr. Fillipatos has provided Committee Member contributions in trials; and has received personal fees from Boehringer Ingelheim during the conduct of the study. Dr. Ferreira is a consultant for Boehringer Ingelheim. Dr. Pocock is a consultant for Boehringer Ingelheim; and has received personal fees from Boehringer Ingelheim during the conduct of the study. Dr. Sattar has consulted for or has received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi; and has received grant support through his institution from Boehringer Ingelheim. Drs. Brueckmann and Jamal, Mr. Cotton, and Ms. Iwata are employees of Boehringer Ingelheim. Dr. Zannad has received steering committee or advisory board fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cardior, CVRx, Janssen, LivaNova, Merck, Mundipharma, Novartis, Novo Nordisk, and Vifor Fresenius; and has received personal fees from Boehringer Ingelheim during the conduct of the study., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We examined the effects of exposure to chronic intermittent hypoxia (CIH) on baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory responses to volume expansion (VE) before and after intrarenal transient receptor potential vanilloid 1 (TRPV1) blockade by capsaizepine (CPZ). Male Wistar rats were exposed to 96 cycles of hypoxia per day for 14 days (CIH) or normoxia. Urine flow and absolute Na + excretion during VE were less in CIH-exposed rats, but the progressive decrease in RSNA during VE was preserved. Assessment of the high-pressure baroreflex revealed an increase in the operating and response range of RSNA and decreased slope in CIH-exposed rats with substantial hypertension [+19 mmHg basal mean arterial pressure (MAP)] but not in a second cohort with modest hypertension (+12 mmHg). Intrarenal CPZ caused diuresis, natriuresis, and a reduction in MAP in sham-exposed (sham) and CIH-exposed rats. After intrarenal CPZ, diuretic and natriuretic responses to VE in CIH-exposed rats were equivalent to those of sham rats. TRPV1 expression in the renal pelvic wall was similar in both experimental groups. Exposure to CIH did not elicit glomerular hypertrophy, renal inflammation, or oxidative stress. We conclude that exposure to CIH 1 ) does not impair the low-pressure baroreflex control of RSNA; 2 ) has modest effects on the high-pressure baroreflex control of RSNA, most likely indirectly due to hypertension; 3 ) can elicit hypertension in the absence of kidney injury; and 4 ) impairs diuretic and natriuretic responses to fluid overload. Our results suggest that exposure to CIH causes renal dysfunction, which may be relevant to obstructive sleep apnea.

Background: Perioperative fluid management - including the type, dose, and timing of administration -directly affects patient outcome after major surgery. The objective of fluid administration is to optimize intravascular fluid status to maintain adequate tissue perfusion. There is continuing controversy around the perioperative use of crystalloid versus colloid fluids. Unfortunately, the importance of fluid volume, which significantly influences the benefit-to-risk ratio of each chosen solution, has often been overlooked in this debate., Main Text: The volume of fluid administered during the perioperative period can influence the incidence and severity of postoperative complications. Regrettably, there is still huge variability in fluid administration practices, both intra-and inter-individual, among clinicians. Goal-directed fluid therapy (GDFT), aimed at optimizing flow-related variables, has been demonstrated to have some clinical benefit and has been recommended by multiple professional societies. However, this approach has failed to achieve widespread adoption. A closed-loop fluid administration system designed to assist anesthesia providers in consistently applying GDFT strategies has recently been developed and tested. Such an approach may change the crystalloid versus colloid debate. Because colloid solutions have a more profound effect on intravascular volume and longer plasma persistence, their use in this more "controlled" context could be associated with a lower fluid balance, and potentially improved patient outcome. Additionally, most studies that have assessed the impact of a GDFT strategy on the outcome of high-risk surgical patients have used hydroxyethyl starch (HES) solutions in their protocols. Some of these studies have demonstrated beneficial effects, while none of them has reported severe complications., Conclusions: The type and volume of fluid used for perioperative management need to be individualized according to the patient's hemodynamic status and clinical condition. The amount of fluid given should be guided by well-defined physiologic targets. Compliance with a predefined hemodynamic protocol may be optimized by using a computerized system. The type of fluid should also be individualized, as should any drug therapy, with careful consideration of timing and dose. It is our perspective that HES solutions remain a valid option for fluid therapy in the perioperative context because of their effects on blood volume and their reasonable benefit/risk profile.

This study aimed to investigate the relationship between intravascular volume and intracardiac filling pressures in stable HF patients with reduced ejection fraction (HFrEF). A total of 40 HFrEF patients (LVEF 36 ± 10%) (10 subjects with a pulmonary artery catheter) underwent intravascular volume expansion with 1 L hydroxyl-ethyl-starch over 3 h with coinciding intravascular volume measurements (technetium (99 tc)-labeled red blood cell technique). Intravascular blood volume increased from 5.0 ± 1.0 L to 5.7 ± 1.0 L (p < 0.0001). No change in clinical status, echocardiographic indices, or cardiac filling pressures was noticed. Invasively measured right atrial pressure and pulmonary arterial wedge pressure increased significantly immediately after start of infusion (4 ± 2 mmHg to 8 ± 4 mmHg; p = 0.01 and 10 ± 3 mmHg to 15 ± 6 mmHg; p = 0.01, respectively), decreased afterwards, and remained stable for 3 h (6 ± 2 mmHg and 14 ± 4 mmHg, respectively). The accuracy of cardiac filling pressure estimates to predict intravascular volume expansion was low (all AUC < 0.65).

Background & Aims: Blood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output., Methods: Healthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging., Results: Ten of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index., Conclusions: A smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid., Trial Registration: The protocol was registered with the European Union Drug Regulating Authorities Clinical Trials Database (https://eudract.ema.europa.eu) (EudraCT No. 2013-003260-32)., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Over 300 million surgical procedures are performed every year worldwide. Anesthesiologists play an important role in the perioperative process by assessing the overall risk of surgery and aim to reduce the risk of complications. Perioperative hemodynamic and volume management can help to improve outcomes in perioperative patients. There has been ongoing discussion about goal-directed therapy. However, there is a consensus that fluid overload and severe fluid depletion in the perioperative period are harmful and can lead to adverse outcomes. This article provides an overview of how to evaluate the fluid responsiveness of patients, details which parameters could be used, and what limitations should be noted.

New Findings: What is the central question of this study? Is it necessary to modify the CO-rebreathing method to acquire reliable measurements of haemoglobin mass in patients with chronic mountain sickness? What is the main finding and its importance? The CO-rebreathing method must be modified because of the prolonged CO-mixing time in patients with chronic mountain sickness. After adaptation of the blood sampling method, reliable and valid results were attained. With this modification, it is possible to quantify the extent of polycythaemia and to distinguish between a haemoconcentration and an exclusive enhancement of erythrocyte volume., Abstract: Patients suffering from chronic mountain sickness (CMS) exhibit extremely high haemoglobin concentrations. Their haemoglobin mass (Hbmass), however, has rarely been investigated. The CO-rebreathing protocol for Hbmass determination in those patients might need to be modified because of restricted peripheral perfusion. The aim of this study was to evaluate the CO uptake and carboxyhaemoglobin-mixing time in the blood of CMS patients and to adapt the CO-rebreathing method for this group. Twenty-five male CMS patients living at elevations between 3600 and 4100 m above sea level were compared with ethnically matched healthy control subjects from identical elevations (n = 11) and near sea level (n = 9) and with a Caucasian group from sea level (n = 6). CO rebreathing was performed for 2 min, and blood samples were taken for the subsequent 30 min. After the method was modified, its reliability was evaluated in test-retest experiments (n = 28), and validity was investigated by measuring the Hbmass before and after the phlebotomy of 500 ml (n = 4). CO uptake was not affected by CMS. The carboxyhaemoglobin mixing was completed after 8 min in the Caucasian group but after 14 min in the groups living at altitude. When blood was sampled 14-20 min after inhalation, the typical error of the method was 1.6% (confidence limits 1.2-2.5%). After phlebotomy, Hbmass decreased from 1779 ± 123 to 1650 ± 129 g, and no difference was found between the measured and calculated Hbmass (1666 ± 122 g). When the time of blood sampling was adapted to accommodate a prolonged carboxyhaemoglobin-mixing time, the CO-rebreathing method became a reliable and valid tool to determine Hbmass in CMS patients., (© 2019 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the Central question? Does dopamine, a pulmonary vascular vasodilator, contribute to the regulation of pulmonary diffusing capacity and capillary blood volume responses to exercise and exercise tolerance? What are the main findings and their importance? Dopamine appears not to be important for regulating pulmonary diffusing capacity or pulmonary capillary blood volume during exercise in healthy participants. Dopamine blockade trials demonstrated that endogenous dopamine is important for maintaining exercise tolerance; however, exogenous dopamine does not improve exercise tolerance., Abstract: Pulmonary capillary blood volume (V c ) and diffusing membrane capacity (D m ) expansion are important contributors to the increased pulmonary diffusing capacity (DL CO ) observed during upright exercise. Dopamine is a pulmonary vascular vasodilator, and recent studies suggest that it may play a role in V c regulation through changes in pulmonary vascular tone. The purpose of this study was to examine the effect of exogenous dopamine and dopamine receptor-2 (D 2 -receptor) blockade on DL CO , V c and D m at baseline and during cycle exercise, as well as time-to-exhaustion at 85% of V ̇ O 2 peak . We hypothesized that dopamine would increase DL CO , V c , D m and time-to-exhaustion, while D 2 -receptor blockade would have the opposite effect. We recruited 14 young, healthy, recreationally active subjects ( V ̇ O 2 peak 45.8 ± 6.6 ml kg -1  min -1 ). DL CO , V c and D m were determined at baseline and during exercise at 60% and 85% of V ̇ O 2 peak under the following randomly assigned and double blinded conditions: (1) intravenous saline and placebo pill, (2) intravenous dopamine (2 µg kg -1  min -1 ) and placebo pill, and (3) intravenous saline and D 2 -receptor antagonist (20 mg oral metoclopramide). Exogenous dopamine and dopamine blockade had no effect on DL CO , V c and D m responses at baseline or during exercise. Dopamine blockade reduced time-to-exhaustion by 47% (P = 0.04), but intravenous dopamine did not improve time-to-exhaustion. While dopamine modulation did not affect DL CO , V c or D m , the reduction in time-to-exhaustion with D 2 -receptor blockade suggests that endogenous dopamine is important for exercise tolerance., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

Background: The primary objective was to compare the effect of a low-dose dexamethasone as against a saline placebo on extravascular lung water index (EVLWI) in patients undergoing elective primary coronary artery bypass surgery. The secondary endpoints were to assess the effect of dexamethasone on other volumetric parameters (pulmonary vascular permeability index, global end diastolic volume index, and intrathoracic blood volume index), Vasoactive Inotrope Scores, hemodynamic parameters and serum osmolality in both groups., Settings and Design: Prospective observational study performed at a single tertiary cardiac care center., Materials and Methods: Twenty patients were randomized to receive either dexamethasone (steroid group, n = 10) or placebo (nonsteroid group, n = 10) twice before the institution of cardiopulmonary bypass (CPB). EVLWI and other volumetric parameters were obtained with the help of VolumeView™ Combo Kit connected to EV 1000 clinical platform at predetermined intervals. Hemodynamic parameters, vasoactive-inotropic Scores, hematocrit values were recorded at the predetermined time intervals. Baseline and 1 st postoperative day serum osmolality values were also obtained., Results: The two groups were evenly matched in terms of demographic and CPB data. Intra- and inter-group comparison of the baseline EVLWI including other volumetric and hemodynamic parameters with those recorded at subsequent intervals revealed no statistical difference and was similar. Generalized estimating equation model was obtained to compare the changes between the groups over the entire study period which showed that on an average the changes between the steroid and nonsteroid group in terms of all volumetric parameters were not statistically significant., Conclusions: There were no beneficial effects of low-dose dexamethasone on EVLWI or other volumetric parameters in patients subjected to on-pump primary coronary bypass surgery. Hemodynamic parameters were also not affected. Probably, the advanced hemodynamic monitoring aided in optimal fluid management in the nonsteroidal group impacting EVLW accumulation.

Purpose: Susceptibility-weighted imaging (SWI) visualizes small cerebral veins with high sensitivity and could, thus, enable quantification of hemodynamics of deep medullary veins. We aimed to evaluate volume changes of deep medullary veins in patients with acute cerebral venous sinus thrombosis (CVST) over time in comparison to healthy controls., Methods: All magnetic resonance imaging (MRI) experiments were executed at 3 T using a 32-channel head coil. Based on SWI and semiautomatic postprocessing (statistical parametric mapping [SPM8] and ANTs), the volume of deep medullary veins was quantified in 14 patients with acute CVST at baseline and the 6‑month follow-up, as well as in 13 healthy controls undergoing repeated MRI examination with an interscan interval of at least 1 month., Results: Deep medullary venous volume change over time was significantly different between healthy controls and patient groups (p < 0.001). Patients with superior sagittal sinus thrombosis (SSST) showed a significant decline from baseline to follow-up measurements (9.8 ± 4.9 ml versus 7.5 ± 4.2 ml; p = 0.02), whereas in patients with transverse sinus thrombosis (TST) and healthy controls no significant volume changes were observable., Conclusions: Venous volume quantification was feasible and reproducible both in healthy volunteers and in patients. The decrease of venous volume in patients over time represents improvement of venous drainage, reduction of congestion, and normalization of microcirculation due to treatment. Thus, quantification of venous microcirculation could be valuable for estimation of prognosis and guidance of CVST therapy in the future.

Aims: In type 2 diabetes impaired insulin-induced muscle perfusion is thought to contribute to reduced whole-body glucose uptake. In this study, we examined the effects of iloprost, a stable prostacyclin analogue, on insulin-induced muscle capillary recruitment and whole-body glucose uptake., Materials and Methods: In a randomized cross-over design, 12 type 2 diabetes patients (age, 55 [46-69] years; BMI, 33.1 [31.0-39] kg/m 2 ) underwent two hyperinsulinaemic-euglycaemic clamps, one with and one without simultaneous low-dose iloprost infusion. Contrast-enhanced ultrasonography of the vastus lateralis muscle was performed before and during the clamp. Muscle capillary recruitment was calculated as percentage change in microvascular blood volume (MBV) before and during the clamp., Results: Insulin infusion reduced skeletal muscle MBV by ~50% compared to the fasting state (fasting, 1.77·10 -4 [1.54·10 -5 -2.44·10 -3 ] arbitrary units (AU); hyperinsulinaemia, 6.69·10 -5 [2.68·10 -6 -5.72·10 -4 ] AU; P = 0.050). Infusion of iloprost prevented this insulin-induced skeletal muscle capillary derecruitment, from (-49.5 [-89.5 to 55.3] %) to (8.0 [-68.8 to 306.6] %), for conditions without and with iloprost, respectively. The rate of glucose disappearance (R d ) did not change significantly during iloprost infusion (17.3 [10.0-40.8] μmol/kg/min) compared with insulin infusion alone (17.6 [9.9-68.7] μmol/kg/min)., Conclusions: Our data suggest that acute improvement in insulin-stimulated muscle perfusion is not an attractive therapeutic approach to bypass cellular resistance to glucose uptake in type 2 diabetes. Whether long-term improvements in insulin-induced muscle perfusion may prove beneficial for glucose disposal remains to be determined., (© 2018 John Wiley & Sons Ltd.)

The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than that of other diuretic classes, results in greater electrolyte-free water clearance and, ultimately, in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling and organ perfusion. We utilize a mathematical model to illustrate that electrolyte-free water clearance results in a greater reduction in IF volume compared to blood volume, and that this difference may be mediated by peripheral sequestration of osmotically inactive sodium. By coupling the model with data on plasma and urinary sodium and water in healthy subjects who received either the SGLT2i dapagliflozin or loop diuretic bumetanide, we predict that dapagliflozin produces a 2-fold greater reduction in IF volume compared to blood volume, while the reduction in IF volume with bumetanide is only 78% of the reduction in blood volume. Heart failure is characterized by excess fluid accumulation, in both the vascular compartment and interstitial space, yet many heart failure patients have arterial underfilling because of low cardiac output, which may be aggravated by conventional diuretic treatment. Thus, we hypothesize that, by reducing IF volume to a greater extent than blood volume, SGLT2 inhibitors might provide better control of congestion without reducing arterial filling and perfusion., (© 2017 John Wiley & Sons Ltd.)

Wheatley, Courtney M., Sarah E. Baker, Bryan J. Taylor, Manda L. Keller-Ross, Steven C. Chase, Alex R. Carlson, Robert J. Wentz, Eric M. Snyder, and Bruce D. Johnson. Influence of inhaled amiloride on lung fluid clearance in response to normobaric hypoxia in healthy individuals. High Alt Med Biol 18:343-354, 2017., Aim: To investigate the role of epithelial sodium channels (ENaC) on lung fluid clearance in response to normobaric hypoxia, 20 healthy subjects were exposed to 15 hours of hypoxia (fraction of inspired oxygen [FiO 2 ] = 12.5%) on two randomized occasions: (1) inhaled amiloride (A) (1.5 mg/5 mL saline); and (2) inhaled saline placebo (P). Changes in lung fluid were assessed through chest computed tomography (CT) for lung tissue volume (TV), and the diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) for pulmonary capillary blood volume (V C ). Extravascular lung water (EVLW) was derived as TV-V C and changes in the CT attenuation distribution histograms were reviewed., Results: Normobaric hypoxia caused (1) a reduction in EVLW (change from baseline for A vs. P, -8.5% ± 3.8% vs. -7.9% ± 5.2%, p < 0.05), (2) an increase in V C (53.6% ± 28.9% vs. 53.9% ± 52.3%, p < 0.05), (3) a small increase in DLCO (9.6% ± 29.3% vs. 9.9% ± 23.9%, p > 0.05), and (4) CT attenuation distribution became more negative, leftward skewed, and kurtotic (p < 0.05)., Conclusion: Acute normobaric hypoxia caused a reduction in lung fluid that was unaffected by ENaC inhibition through inhaled amiloride. Although possible amiloride-sensitive ENaC may not be necessary to maintain lung fluid balance in response to hypoxia, it is more probable that normobaric hypoxia promotes lung fluid clearance rather than accumulation for the majority of healthy individuals. The observed reduction in interstitial lung fluid means alveolar fluid clearance may not have been challenged.

Context: Curcumin has been reported to have anti-inflammatory, antioxidant and hypoglycaemic properties, besides reducing mortality in sepsis., Objective: This study evaluates the biological activities of a curcumin dispersion formulated by spray-drying in experimental sepsis., Materials and Methods: Male Wistar rats were subjected to sepsis by caecal ligation and puncture (CLP), controls were sham operated. The animals were treated with curcumin dispersion (100 mg/kg, p.o.) or water for 7 days prior to CLP and at 2 h after surgery. One group was used to analyze curcumin absorption through HPLC; another had the survival rate assessed during 48 h; and from a third group, blood was collected by decapitation to analyze metabolic and inflammatory parameters., Results: The plasma curcumin levels reached 2.5 ng/mL at 4 h, dropped significantly (p < 0.001) at 6 h (1.2 ng/mL), and were undetectable at 24 h in both groups. Curcumin temporarily increased the survival rate of the septic rats by 20%. Moreover, it attenuated glycaemia (p < 0.05) and volemia (p < 0.05) alterations typically observed during sepsis, and decreased the levels of the proinflammatory cytokines IL-1β and IL-6 in plasma (p < 0.001) and peritoneal lavage fluid (p < 0.05) of septic rats. Serum HSP70 levels were decreased (p < 0.01) at 24 h after CLP., Discussion and Conclusion: Our results show that the curcumin dispersion dose employed was not detrimental to the septic rats. In fact, it temporarily increased their survival rate, improved important metabolic parameters, reduced proinflammatory cytokines and HSP70 production.

It was the purpose to quantify the hemodynamic effects of a bolus of hypertonic glucose injected into the extracorporeal system in a group of stable and nondiabetic patients during hemodialysis (HD). Glucose and electrolytes were measured in frequent intervals. Arterial blood pressures and heart rates were continuously recorded by noninvasive vascular unloading technique. Beat-to-beat stroke volume, cardiac output, and total peripheral resistance were determined by Modelflow method. Relative blood volumes were continuously measured by ultrasonic and optical means. Eight patients were studied in two treatments. Although arterial pressures and heart rates remained stable, stroke volume and cardiac output transiently increased above (19.2 ± 12.3%) and total peripheral resistance dropped below baseline (18.2 ± 8.6%) by a comparable magnitude. Relative blood volume transiently increased above baseline at 100% (104.9 ± 1.0%). Glucose concentrations were significantly related to relative blood volumes (r = 0.86, p < 0.001). In spite of a substantial increase in blood volume, a bolus of hypertonic glucose does not increase arterial pressures in nondiabetic patients because of concomitant vasodilatation. The relative increase in blood volume quantified by noninvasive HD technology follows the course of glucose and could be used as a surrogate to characterize patients with regard to their glucose metabolism during HD.

There is evidence to suggest athletes have adopted recombinant human erythropoietin (rHuEPO) dosing regimens that diminish the likelihood of being caught by direct detection techniques. However, the temporal response in physiology, performance, and Athlete Biological Passport (ABP) parameters to such regimens is not clearly understood. Participants were assigned to a high-dose only group (HIGH, n = 8, six rHuEPO doses of 250 IU/kg over two weeks), a combined high micro-dose group (COMB, n = 8, high-dose plus nine rHuEPO micro-doses over a further three weeks), or one of two placebo control groups who received saline in the same pattern as the HIGH (HIGH-PLACEBO, n = 4) or COMB (COMB-PLACEBO, n = 4) groups. Temporal changes in physiology and performance were tracked by graded exercise test (GXT) and haemoglobin mass assessment at baseline, after high dose, after micro-dose (COMB and COMB-PLACEBO only) and after a four-week washout. Venous blood samples were collected throughout the baseline, rHuEPO administration, and washout periods to determine the haematological and ABP response to each dosing regimen. Physiological adaptations induced by a two-week rHuEPO high-dose were maintained by rHuEPO micro-dosing for at least three weeks. However, all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods. These results indicate there is sufficient sensitivity in the ABP to detect use of high rHuEPO doping regimens in athletic populations and they provide important empirical examples for use by anti-doping experts. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Untreated and preclinical heart failure patients with reduced ejection fraction (HFrEF) have an impaired ability to alleviate excess intravascular volume., Objectives: To investigate 1) the renal response to intravascular volume expansion in euvolemic and optimally treated HFrEF patients and 2) loop diuretic efficiency., Methods: 14 healthy and 28 HFrEF patients underwent intravascular volume expansion with 1l hydroxyl ethyl starch 6% during 3h after which a loop diuretic was administered. Clinical parameters, neurohormones and urine were hourly measured., Results: In response to intravascular volume expansion (+0.6±0.2L; p<0.001 vs baseline) HFrEF patients demonstrated significantly lower natriuresis compared to healthy subjects (0.9±0.5 versus 1.7±0.6g/3h; p<0.001). However, natriuresis varied substantially with half of HFrEF patients exhibiting a response within the range of healthy and the other half demonstrating a significantly decreased response (1.4±0.4 vs 0.5±0.2g/3h; p<0.001). Natriuresis was associated with glomerular filtration function (eGFR), NT-proBNP and tubular fractional sodium excretion (FE Na ). Loop diuretic efficiency was significantly lower in HFrEF patients compared to healthy subjects (3.4±0.7 vs 2.6±1.1g/2h; p=0.044) but was only related to eGFR (R 2 =0.47; p<0.001) and independent of FE Na (R 2 =0.07; p=0.20). Loop diuretics increased FE Na similarly in healthy subjects and HFrEF patients (9.1±2.4 vs 9.3±3.3%; p=0.64)., Conclusion: The ability of the kidneys to remove excess intravascular volume is decreased in a substantial amount of euvolemic and optimally treated HFrEF patients. Renal response relates to filtration function and tubular sodium handling. In contrast, loop diuretics can surmount decreased renal tubular sodium excretion but remain dependent on eGFR., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Traumatic brain injury (TBI) and hemorrhagic shock due to uncontrolled bleeding are the major causes of death after severe trauma. Mortality rates are threefold higher in patients suffering from multiple injuries and additionally TBI. Factors known to impair outcome after TBI, namely hypotension, hypoxia, hypercapnia, acidosis, coagulopathy and hypothermia are aggravated by the extent and severity of extracerebral injuries. The mainstays of TBI intensive care may be, at least temporarily, contradictory to the trauma care concept for multiple trauma patients. In particular, achieving normotension in uncontrolled bleeding situations, maintenance of normocapnia in traumatic lung injury and thromboembolic prophylaxis are prone to discussion. Due to an ongoing uncertainty about the definition of normotensive blood pressure values, a cerebral perfusion pressure-guided cardiovascular management is of key importance. In contrast, there is no doubt that early goal directed coagulation management improves outcome in patients with TBI and multiple trauma. The timing of subsequent surgical interventions must be based on the development of TBI pathology; therefore, intensive care of multiple trauma patients with TBI requires an ongoing and close cooperation between intensivists and trauma surgeons in order to individualize patient care.

The clinical course of schizophrenia is characterized by recurrence and chronicity and has a large burden on society.　Nevertheless, diagnosis of schizophrenia is based only on distinctive symptoms and the disease course.　Near-infrared spectroscopy (NIRS) is a useful method for measuring changes in the hemoglobin concentration in the cortical surface area and reflects brain function.　We measured NIRS four times during the clinical course in a patient with first-episode schizophrenia.A 17-year-old woman admitted to our hospital because of hallucinations, delusions and appetite loss. After treatment with low-dose antipsychotics, NIRS findings showed a prompt increase in the cerebral blood volume in the frontal region.　On the basis of the clinical course of this patient, we introduce a new point of view, namely, that NIRS findings may be useful as a state marker that indicates the severity of schizophrenia in some cases.

Background: Xuesaitong dispersible tablet (XST) product has been clinically proven to be effective for treating cardio-cerebrovascular disease. Furthermore, herb-drug interactions between the XST product and drugs that are commonly co-administered, such as aspirin (ASA), must be explored to ensure safe clinical use., Study Design and Methods: The current study aims to investigate whether the XST product interacts with ASA when they are administered concomitantly to ensure safety and efficacy. A ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of ginsenoside Rg1 (Rg1), ginsenoside Rd (Rd), notoginsenoside R1 (R1) and salicylic acid (SA) in rat plasma to investigate the pharmacokinetic interaction of XST and ASA in blood stasis model rats., Results and Conclusion: The ASA and XST combination noticeably altered R1 and Rg1 absorption, distribution and disposition. This study indicates that co-administration of XST and ASA can cause an apparent herb-drug pharmacokinetic interaction in blood stasis model rats., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Background:: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways., Objective:: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE., Methods:: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE., Results:: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32)., Discussion:: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables., Conclusion:: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats., Fundamento:: Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas., Objetivo:: Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC., Métodos:: Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC., Resultados:: Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32)., Discussão:: O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis., Conclusão:: Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.

Objective: To evaluate the effects of polyethylene oxide (PEO) on blood perfusion in hind limb skeletal muscles in a rat model of chronic hind limb ischemia., Methdos: Twelve rat models of chronic hind limb ischemia established by unilateral femoral artery ligation were randomized into PEO and control groups (n=6) and treated with intravenous infusion of PEO and saline through the internal jugular vein every other day for 2 weeks. Contrast-enhanced ultrasonography was performed after the treatments to evaluate the blood flow in the skeletal muscles at different time points and blood flow reserve in the ischemic hind limbs on day 28., Results: Starting from 7 days after femoral artery ligation, blood flow in the ischemic hind limb skeletal muscles was significantly higher in PEO group than in the control group (P<0.05). On day 28, blood flow reserve in the ischemic hind limb was significantly higher (P=0.012), and blood volume was significantly increased in PEO group as compared that in the control group (P=0.024)., Conclusions: PEO can increase blood flow, blood flow reserve and vascular volume in the hind limb skeletal muscles in rats with chronic hind limb ischemia, suggesting that PEO can promote angiogenesis and arterial formation by increasing blood flow shear stress to improve blood supply of ischemic hind limbs.

Background: Neovascularization, a distinguishing trait of high-grade glioma, is a target for anti-angiogenic treatment with bevacizumab (BEV). This study sought to use ferumoxytol-based dynamic susceptibility contrast magnetic resonance imaging (MRI) to clarify perfusion and relative blood volume (rCBV) changes in glioma treated with BEV and to determine potential impact on clinical management., Methods: 16 high grade glioma patients who received BEV following post-chemoradiation radiographic or clinical progression were included. Ferumoxytol-based MRI perfusion measurements were taken before and after BEV. Lesions were defined at each timepoint by gadolinium-based contrast agent (GBCA)-enhancing area. Lesion volume and rCBV were compared pre and post-BEV in the lesion and rCBV "hot spot" (mean of the highest rCBV in a 1.08 cm 2 area in the enhancing volume), as well as hypoperfused and hyperperfused subvolumes within the GBCA-enhancing lesion., Results: GBCA-enhancing lesion volumes decreased 39% (P = 0.01) after BEV. Mean rCBV in post-BEV GBCA-enhancing area did not decrease significantly (P = 0.227) but significantly decreased in the hot spot (P = 0.046). Mean and hot spot rCBV decreased (P = 0.039 and 0.007) when post-BEV rCBV was calculated over the pre-BEV GBCA-enhancing area. Hypoperfused pixel count increased from 24% to 38 (P = 0.007) and hyperperfused decreased from 39 to 28% (P = 0.017). Mean rCBV decreased in 7/16 (44%) patients from >1.75 to <1.75, the cutoff for pseudoprogression diagnosis., Conclusions: Decreased perfusion after BEV significantly alters rCBV measurements when using ferumoxytol. BEV treatment response hinders efforts to differentiate true progression from pseudoprogression using blood volume measurements in malignant glioma, potentially impacting patient diagnosis and management.

It is widely held that in response to high salt diets, normal individuals are acutely and chronically resistant to salt-induced hypertension because they rapidly excrete salt and retain little of it so that their blood volume, and therefore blood pressure, does not increase. Conversely, it is also widely held that salt-sensitive individuals develop salt-induced hypertension because of an impaired renal capacity to excrete salt that causes greater salt retention and blood volume expansion than that which occurs in normal salt-resistant individuals. Here we review results of both acute and chronic salt-loading studies that have compared salt-induced changes in sodium retention and blood volume between normal subjects (salt-resistant normotensive control subjects) and salt-sensitive subjects. The results of properly controlled studies strongly support an alternative view: during acute or chronic increases in salt intake, normal salt-resistant subjects undergo substantial salt retention and do not excrete salt more rapidly, retain less sodium, or undergo lesser blood volume expansion than do salt-sensitive subjects. These observations: (i) directly conflict with the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension, and (ii) have implications for contemporary understanding of how various genetic, immunologic, and other factors determine acute and chronic blood pressure responses to high salt diets., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The inability to augment capillary blood volume (CBV) in response to insulin or glucose is thought to contribute to insulin resistance (IR) by limiting glucose uptake in key storage sites. Understanding the mechanisms that contribute to impaired CBV augmentation early in the onset of IR may lead to new future therapies. We hypothesized that inactivity alters the balance of vasoactive eicosanoids and contributes to microvascular IR. In ten activity-restricted (AR) and six normal activity adult male rhesus macaques, contrast-enhanced ultrasound of skeletal muscle blood flow and CBV was performed at baseline and during intravenous glucose tolerance test (IVGTT). Plasma was analyzed for vasoconstrictor hydroxyeicosatetraenoic acids (HETEs) and the ratio of vasodilatory epoxyeicosatrienoic acids (EETs) to their less biologically active dihydroxyeicosatrienoic acids (DHETs) as an indirect measure of soluble epoxide hydrolase activity. AR primates were IR during IVGTT and had a 45% lower glucose-stimulated CBV response. Vasoconstrictor 18-HETE and 19-HETE and the DHET/EET ratio were markedly elevated in the AR group and correlated inversely with the CBV response. In addition, levels of 18-HETE and 19-HETE correlated directly with microvascular IR. We conclude that a shift toward increased eicosanoid vasoconstrictor tone correlates with abnormal skeletal muscle vascular recruitment and may contribute to IR., Competing Interests: There are no conflicts for any of the authors of this study.

Background: The revised Starling law suggests that intravenously infused fluid may leak into the interstitium and not remain in the intravascular space. This hypothesis is supported by clinical findings that postoperative weight gain is proportional to the amount of infused fluid. The distribution of intravenously administered fluid between the interstitium and intravascular space deserves evaluation, as postoperative weight gain because of intraoperative infusion is an important risk factor for postoperative adverse events. We quantitatively estimated fluid movement in patients undergoing orthognathic surgery by performing a volume kinetic study using hemoglobin concentration as a marker of dilution., Methods: Forty-one patients scheduled to undergo orthognathic surgery were enrolled in this study. The arterial hemoglobin concentration was measured at each procedural step. Acute normovolemic hemodilution was induced by withdrawing 400 mL of blood followed by the infusion of a known amount of hydroxyethyl starch, enabling the initial blood volume to be estimated. The dilution rate of the arterial hemoglobin concentration enabled the volume of fluid in the intravascular space to be quantified. The fluid volume that leaked into the interstitium was then calculated based on the change in the estimated intravascular plasma volume., Results: The blood volume estimated via this method was close to the value derived from a previously published formula. The mean volume of crystalloid infused as a maintenance fluid was 2062 ± 408 mL, ranging from 1220 to 3050 mL. None of the cases required blood product transfusion. The amount of infused fluid that remained intravascular varied widely from 2.0 to 35.7 mL/kg (mean, 12.0 ± 8.2 mL) after surgery, corresponding to 5.3% to 95.7% of the infused volume. The change in intravascular fluid volume during surgery was not strongly correlated with the infusion amount (Pearson correlation analysis: r = -0.05, P = .75, -0.44 < ρ ≤ 0.35, confidence intervals; Spearman correlation analysis: r = -0.14, P = .38, -0.51 < ρ ≤ 0.27). However, the amount of fluid that leaked into the interstitium during surgery did correlate with the infusion amount (Pearson correlation analysis: r = 0.42, P = .01, 0.03 < ρ ≤ 0.70; Spearman correlation analysis: r =0.45, P = .003, 0.07 < ρ ≤ 0.72)., Conclusions: We found that the increase in intravascular fluid volume caused by intravenous fluid administration was not correlated strongly with the volume of infused fluid. Instead, the amount of fluid leakage into the interstitial space depended on the infused fluid volume. This clinical result supports the revised Starling law, which suggests that intravascular fluid may often leak into the interstitium. More work is needed to better understand the factors governing leakage of infused fluid into the interstitial space.

Purpose:: To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage., Methods:: Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed., Results:: Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups., Conclusion:: The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.

Objective: Monitoring of patient's intravascular volume status without invasive measures remains challenging and unreliable. Our objective was to determine if corrected flow time (FTc) measurement could detect preload reduction with administration of nitroglycerin (NTG) as a surrogate for volume loss., Methods: Post hoc FTc analysis was performed for a prospective cohort study of pulsed wave spectral Doppler measurements before and after administration of NTG. Patients enrolled were eligible for inclusion if they were admitted to a chest pain center for cardiac evaluation. Descriptive statistics, t tests, bivariate regression, and intraclass correlation coefficient were performed as appropriate., Results: Fifty-four patients had Doppler measurements available for review. Mean FTc decreased from 339 milliseconds (95% confidence interval, 332-346) to 325 milliseconds (95% confidence interval, 318-331) with administration of 0.3 mg of sublingual NTG (P=.0001). Mean heart rate increased 5 beats/min with administration of NTG (P<.0001); however, there was no significant change in systolic or diastolic blood pressure., Conclusion: Corrected flow time was able to detect a significant difference in preload reduction with 0.3 mg of NTG. The FTc may be an early reliable noninvasive measure to detect changes in intravascular volume status., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Rapid fluid infusion resulting in increased hepatic blood flow may decrease the propofol plasma concentration (Cp) because propofol is a high hepatic extraction drug. The authors investigated the effects of rapid colloid and crystalloid infusions on the propofol Cp during target-controlled infusion., Methods: Thirty-six patients were randomly assigned to 1 of 3 interventions (12 patients per group). At least 30 min after the start of propofol infusion, patients received either a 6% hydroxyethyl starch (HES) solution at 24 ml·kg·h or acetated Ringer's solution at 24 or 2 ml·kg·h during the first 20 min. In all groups, acetated Ringer's solution was infused at 2 ml·kg·h during the next 20 min. The propofol Cp was measured every 2.5 min as the primary outcome. Cardiac output, blood volume, and indocyanine green disappearance rate were determined using a pulse dye densitogram analyzer before and after the start of fluid administration. Effective hepatic blood flow was calculated as the blood volume multiplied by the indocyanine green disappearance rate., Results: The rapid HES infusion significantly decreased the propofol Cp by 22 to 37%, compared to the Cp at 0 min, whereas the rapid or maintenance infusion of acetate Ringer's solution did not decrease the propofol Cp. Rapid HES infusion, but not acetate Ringer's solution infusion, increased the effective hepatic blood flow., Conclusions: Rapid HES infusion increased the effective hepatic blood flow, resulting in a decreased propofol Cp during target-controlled infusion. Rapid HES infusion should be used cautiously as it may decrease the depth of anesthesia.

Background: Although arterial hypotension occurs frequently with propofol use in humans, its effects on intravascular volume and vascular capacitance are uncertain. We hypothesized that propofol decreases vascular capacitance and therefore decreases stressed volume., Methods: Cardiac output (CO) was measured using Modelflow(®) in 17 adult subjects after upper abdominal surgery. Mean systemic filling pressure (MSFP) and vascular resistances were calculated using venous return curves constructed by measuring steady-state arterial and venous pressures and CO during inspiratory hold manoeuvres at increasing plateau pressures. Measurements were performed at three incremental levels of targeted blood propofol concentrations., Results: Mean blood propofol concentrations for the three targeted levels were 3.0, 4.5, and 6.5 µg ml(-1). Mean arterial pressure, central venous pressure, MSFP, venous return pressure, Rv, systemic arterial resistance, and resistance of the systemic circulation decreased, stroke volume variation increased, and CO was not significantly different as propofol concentration increased., Conclusions: An increase in propofol concentration within the therapeutic range causes a decrease in vascular stressed volume without a change in CO. The absence of an effect of propofol on CO can be explained by the balance between the decrease in effective, or stressed, volume (as determined by MSFP), the decrease in resistance for venous return, and slightly improved heart function., Clinical Trial Registration: Netherlands Trial Register: NTR2486., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ∼7.5 mmol·L(-1)) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-(13)C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism.

Background: Crystalloid fluid requires 30 min for complete distribution throughout the extracellular fluid space and tends to cause long-standing peripheral edema. A kinetic analysis of the distribution of Ringer's acetate with increasing infusion rates was performed to obtain a better understanding of these characteristics of crystalloids., Methods: Data were retrieved from six studies in which 76 volunteers and preoperative patients had received between 300 ml and 2375 ml of Ringer's acetate solution at a rate of 20-80 ml/min (0.33-0.83 ml/min/kg). Serial measurements of the blood hemoglobin concentration were used as inputs in a kinetic analysis based on a two-volume model with micro-constants, using software for nonlinear mixed effects., Results: The micro-constants describing distribution (k12) and elimination (k10) were unchanged when the rate of infusion increased, with half-times of 16 and 26 min, respectively. In contrast, the micro-constant describing how rapidly the already distributed fluid left the peripheral space (k21) decreased by 90% when the fluid was infused more rapidly, corresponding to an increase in the half-time from 3 to 30 min. The central volume of distribution (V(c)) doubled., Conclusion: The return of Ringer's acetate from the peripheral fluid compartment to the plasma was slower with high than with low infusion rates. Edema is a normal consequence of plasma volume expansion with this fluid, even in healthy volunteers. The results are consistent with the view that the viscoelastic properties of the interstitial matrix are responsible for the distribution and redistribution characteristics of crystalloid fluid., (© 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: We hypothesized that the relative cerebral blood volume (rCBV) ratio on perfusion-weighted imaging (PWI) using MRI might serve as a predictor of early recanalization (ER) after intravenous tissue plasminogen activator (IV t-PA) administration for acute ischemic stroke., Methods: Patients with acute middle cerebral artery (MCA) ischemic stroke (IS) were enrolled in the study. They were evaluated by MRI, including PWI and diffusion-weighted imaging, before administration of IV t-PA and underwent digital subtraction angiography (DSA) of the brain within 2 h after t-PA administration. We compared the rCBV ratio on PWI between patients with and without ER on DSA and investigated the proportion of patients with an excellent outcome at 90 days after t-PA administration (modified Rankin Scale score 0-1) among those with and without ER., Results: 85 patients with acute MCA IS were included; 16 patients (18.8%) experienced ER on DSA after IV t-PA administration. Patients with ER more frequently had an excellent outcome at 90 days than those without ER. The rCBV ratio on PWI was higher in the ER group (1.01±0.21, p<0.01) than in the non-ER group (0.82±0.18). After adjusting for the presence of atrial fibrillation and the serum glucose level, the rCBV ratio on PWI (OR 1.07; 95% CI 1.02 to 1.12; p<0.01) was a significant independent indicator of ER., Conclusions: The results of this study suggest that the rCBV ratio on PWI might serve as a useful indicator of ER after IV t-PA administration., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Introduction: The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned., Methods: 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded., Results: Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS ≤ 2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome., Conclusions: Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.

Splanchnic circulation is the primary mechanism that regulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods (e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure.

Objective: The purpose of this study is to compare estimated blood volume (EBV) versus weight-based (WB) dosing of unfractionated heparin in terms of safety and ability to achieve therapeutic antifactor-Xa (AF-Xa) levels., Methods: This was a retrospective, cohort study including 32 male veterans who received UFH. Primary outcome measures included time until therapeutic anticoagulation, number of adjustments needed to achieve therapeutic anticoagulation, median AF-Xa levels and the percentage of patients who were therapeutic after the first and second levels. Safety was determined as the incidence of major and minor bleeding., Results: EBV dosing may be associated with a decrease in the average time to therapeutic range (20.4 ± 16.7 hours with EBV vs. 26.8 ± 26 hours with WB; p = 0.404) and an increase in the percentage of patients achieving therapeutic anticoagulation after the first AF-Xa level (50% with EBV vs. 35.7% with WB; p = 0.611) although these results were not statistically significant. WB dosing required fewer adjustments (2.7 ± 2.9 with WB vs. 4 ± 2.6 with EBV; p = 0.192) with more patients within the therapeutic range after the second AF-Xa level (42.9% with WB vs. 33.3% with EBV; p = 0.897). There was one major and three minor bleeds in the WB dosing group versus one minor bleed for the EBV dosing cohort (p = 0.438 and p = 0.323, respectively)., Conclusion: EBV dosing achieved quick therapeutic anticoagulation with less bleeding compared to WB dosing in a veteran population. Due to the study's limitations, larger, randomized, comparative trials are needed to confirm our findings., (Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Introduction: The objective of this study was to test whether stroke volume (SV) variations in response to a fixed mini-fluid challenge (ΔSV100) measured by impedance cardiography (ICG) could predict an increase in arterial pressure with volume expansion in spontaneously breathing patients under spinal anaesthesia., Methods: Thirty-four patients, monitored by ICG who required intravenous fluid to expand their circulating volume during surgery under spinal anaesthesia, were studied. Haemodynamic variables and bioimpedance indices (blood pressure, SV, cardiac output [CO]) were measured before and after fluid challenge with 100mL of crystalloid, and before/after volume expansion. Responders were defined by ≥15% increase in systolic arterial pressure (SAP) after infusion of 500 mL of crystalloid solution., Results: SAP increased by ≥15% in 20 (59%) of the 34 patients. SAP, SV, and CO increased and HR decreased only in responders. SV variations in response to mini-fluid challenge and volume expansion differed between patients who showed arterial responsiveness and those in whom SAP did not increase with volume expansion (11.6% [9.1-19.3] versus 2.5% [1.3-7], P<0.001, and 22.4% [11.7-36.6] versus 0.9 [0-5.5], P<0.001, respectively). ΔSV100 predicted an increase of arterial pressure with an area under the receiver operating characteristic (AUC) curve of 0.89 (CI95%: 0.73-0.97, P<0.001). The cut-off was 5%. Baseline SAP and HR were not predictive of arterial responsiveness (P>0.05)., Conclusion: A ΔSV100 over 5% accurately predicted arterial pressure response to volume expansion during surgery., (Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: Neurointerventionalists do not agree about the optimal imaging protocol when evaluating patients with acute stroke for potential endovascular revascularization. Preintervention cerebrovascular blood volume (CBV) has been shown to predict outcomes in patients undergoing intra-arterial stroke therapies., Objective: To determine whether CBV can predict hemorrhagic transformation and clinical outcomes in patients selected for endovascular therapy for acute ischemic middle cerebral artery (MCA) stroke using a CT perfusion (CTP)-based imaging protocol., Methods: We retrospectively reviewed cases of acute ischemic stroke due to MCA M1 segment occlusion and correlated favorable clinical outcomes (modified Rankin scale (mRS) ≤2) and radiographic outcomes with preintervention CBV values. All patients underwent whole-brain (320-detector-row) CTP imaging, and absolute CBV values of the affected and contralateral MCA territories were obtained separately for the cortical and basal ganglia regions., Results: Relative CBV (rCBV) of the MCA cortical regions was significantly lower in patients with poor clinical outcomes than in those with favorable clinical outcomes (0.87±0.21 vs 1.02±0.09, p=0.0003), and a negative correlation was found between rCBV values and mRS score severity. rCBV of the basal ganglia region was significantly lower in patients with hemorrhagic infarction (p=0.004) and parenchymal hematoma (p=0.04) than in those without hemorrhagic transformation., Conclusions: We found that cortical CBV loss is predictive of poor clinical outcomes, whereas basal ganglia CBV loss is predictive of hemorrhagic transformation but without translation into poor clinical outcomes. Our study findings support published results of baseline preintervention CBV as a predictor of outcomes in patients undergoing intra-arterial stroke therapies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)