Novel functions of the anion exchanger AE4 (SLC4A9).

The kidney plays a crucial role in acid-base homeostasis. In the distal nephron, α-intercalated cells contribute to urinary acid (H+) secretion and ß-intercalated cells accomplish urinary base (HCO3-) secretion. ß-intercalated cells regulate the acid base status through modulation of the apical Cl-/HCO3- exchanger pendrin (SLC26A4) activity. In this review, we summarize and discuss our current knowledge of the physiological role of the renal transporter AE4 (SLC4A9). The AE4, as cation-dependent Cl-/HCO3- exchanger, is exclusively expressed in the basolateral membrane of ß-intercalated cells and is essential for the sensing of metabolic acid-base disturbances in mice, but not for renal sodium reabsorption and plasma volume control. Potential intracellular signaling pathways are discussed that might link basolateral acid-base sensing through the AE4 to apical pendrin activity.

Study of the f-cell ratio using plasma dilution and albumin mass kinetics.

BACKGROUND: The f-cell ratio of 0.91 is a conversion factor between the hematocrit measured in peripheral blood and the hematocrit obtained by separate measurements of the red blood cell mass and plasma volume. The physiological background of the f-cell ratio is unclear. METHODS: Data were retrieved from 155 intravenous infusion experiments where 15-25 mL/kg of crystalloid fluid diluted the blood hemoglobin and plasma albumin concentrations. The hemodilution was converted to plasma dilution using the peripheral hematocrit, and the volume of distribution of exogenous albumin was calculated in 41 volunteers who received 20 % or 5 % albumin by intravenous infusion. Finally, the kinetics of plasma albumin was studied during 98 infusion experiments with 20 % albumin. RESULTS: Plasma dilution based on hemoglobin and albumin showed a median difference of -0.001 and a mean difference of 0.000 (N = 2184), which demonstrates that these biomarkers indicate the same expandable vascular space. In contrast, exogenous albumin occupied a volume that was 10 % larger than the plasma volume indicated by the anthropometric equations of Nadler et al. and Retzlaff et al. The kinetic analysis identified a secondary compartment that was 450 mL in size and rapidly exchanged albumin with the circulating plasma. CONCLUSIONS: The results suggest that the f-cell ratio is due to rapid exchange of albumin between the plasma and a non-expandable compartment located outside the circulating blood (possibly the liver sinusoids). This means that the hematocrit measured in peripheral blood correctly represents the ratio between the red cell volume and the circulating plasma volume.

Blood volume and hemodynamics during treatment of major hemorrhage with Ringer solution, 5% albumin, and 20% albumin: a single-center randomized controlled trial.

BACKGROUND: Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable option to maintain the blood volume during surgery associated with major hemorrhage. Therefore, the aim of this study was to quantify and compare the plasma volume expansion properties of 5% albumin, 20% albumin, and Ringer-lactate, when infused during major surgery. METHODS: In this single-center randomized controlled trial, fluid replacement therapy to combat hypovolemia during the hemorrhagic phase of cystectomy was randomly allocated in 42 patients to receive either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min at the beginning of the hemorrhagic phase, both completed by a Ringer-lactate replacing blood loss in a 1:1 ratio, or Ringer-lactate alone to replace blood loss in a 3:1 ratio. Measurements of blood hemoglobin over 5 h were used to estimate the effectiveness of each fluid to expand the blood volume using the following regression equation: blood loss plus blood volume expansion = factor + volume of infused albumin + volume of infused Ringer-lactate. RESULTS: The median hemorrhage was 848 mL [IQR: 615-1145]. The regression equation showed that the Ringer-lactate solution expanded the plasma volume by 0.18 times the infused volume while the corresponding power of 5% and 20% albumin was 0.74 and 2.09, respectively. The Ringer-lactate only fluid program resulted in slight hypovolemia (mean, - 313 mL). The 5% and 20% albumin programs were more effective in filling the vascular system; this was evidenced by blood volume changes of only + 63 mL and - 44 mL, respectively, by long-lasting plasma volume expansion with median half time of 5.5 h and 4.8 h, respectively, and by an increase in the central venous pressure. CONCLUSION: The power to expand the plasma volume was 4 and almost 12 times greater for 5% albumin and 20% albumin than for Ringer-lactate, and the effect was sustained over 5 h. The clinical efficacy of albumin during major hemorrhage was quite similar to previous studies with no hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov NCT05391607, date of registration May 26, 2022.

Predictive value of estimated plasma volume for postoperative hypotension in percutaneous intramyocardial septal radiofrequency ablation treating for hypertrophic obstructive cardiomyopathy.

BACKGROUND: Estimated plasma volume status (ePVS) estimated by the Duarte formula is associated with clinical outcomes in patients with heart failure. It remains unclear the predictive value of the ePVS to the postoperative hypotension (POH) in percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) treating hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Data of HOCM patients who underwent PIMSRA were retrospectively collected. Preoperative ePVS was calculated using the Duarte formulas which derived from hemoglobin and hematocrit ratios. Clinical variables including physical assessment, biological and echocardiographic parameters were recorded. Patients were labeled with or without POH according to the medical record in the hospital. Univariable and multivariable logistic regression were performed to evaluate the association between ePVS and POH. Using different thresholds derived from quartiles and the best cutoff value of the receiver operating characteristic curve, the diagnostic performance of ePVS was quantified. RESULTS: Among the 405 patients included in this study, 53 (13.1%) patients were observed with symptomatic POH. Median (IQR) of ePVS in overall patients was 3.77 (3.27~4.40) mL/g and in patients with POH were higher than those without POH. The ePVS was associated with POH, with the odds ratio of 1.669 (95% CI 1.299 ~ 2.144) per mL/g. After adjusted by potential confounders, ePVS remained independently associated with POH, with the approximate odds ratio in different models. CONCLUSION: The preoperative ePVS derived from the Duarte formulas was independently associated with postoperative hypotension in HOCM patients who underwent PIMSRA and showed prognostic value to the risk stratification of postoperative management. TRIAL REGISTRATION: NCT06003478 (22/08/2023).

Calculated plasma volume status in hemodialysis patients.

BACKGROUND: Plasma volume (PV) calculated from hematocrit and body weight has applications in cardiovascular disease. The current study investigated the validity of the calculated PV for predicting volume overload and its prognostic utility in patients undergoing hemodialysis (HD). PATIENTS AND METHODS: Fifty-four HD patients were prospectively enrolled, and their actual PV (aPV) and relative PV status (PVS) were calculated. Bioelectrical impedance analysis (BIA) with assessment of and total body water (TBW), intracellular water (ICW), extracellular water (ECW), and overhydration (OH) and routine blood examinations were performed before dialysis. A second cohort of 164 HD patients was retrospectively enrolled to evaluate the relationship between the calculated PVS and the outcome, with an endpoint of all-cause mortality. RESULTS: aPV was significantly associated with TBW, ICW, ECW, OH, and ECW/TBW (all p < 0.001), and most strongly with ECW (r = 0.83). aPV predicted the extent of volume overload with an AUC of 0.770 (p < 0.001), but PVS did not (AUC = 0.617, p = 0.091). Median follow-up time was 53 months, during the course of which 60 (36.58%) patients died. Values for PVS (12.94 ± 10.87% vs. 7.45 ± 5.90%, p = 0.024) and time-averaged PVS (12.83 ± 11.20 vs. 6.78 ± 6.22%, p < 0.001) were significantly increased in patients who died relative to those who survived. A value of time-averaged PVS >8.72% was significantly associated with an increased incidence of all-cause mortality (HR = 2.48, p = 0.0023). CONCLUSIONS: aPV was most strongly associated with ECW measured using BIA. HD patients with higher time-averaged PVS had a higher rate of all-cause mortality.

The effects of empagliflozin on measured glomerular filtration rate and estimated extracellular and plasma volumes in patients with type 2 diabetes.

AIMS: To investigate the effects of empagliflozin on measured glomerular filtration rate (mGFR), estimated plasma volume (PV) and estimated extracellular volume (ECV) in a cohort of patients with type 2 diabetes (T2D) and high risk of cardiovascular events. MATERIALS AND METHODS: In this prespecified substudy of the randomized, placebo-controlled SIMPLE trial, patients with T2D at high risk of cardiovascular events were allocated to either empagliflozin 25 mg or placebo once daily for 13 weeks. The prespecified outcome was between-group change in mGFR, measured by the 51 Cr-EDTA method after 13 weeks; changes in estimated PV and estimated ECV were included. RESULTS: From April 4, 2017 to May 11, 2020, 91 participants were randomized. Of these, 45 patients from the empagliflozin group and 45 patients from the placebo group were included in the intention-to-treat analysis. Treatment with empagliflozin reduced mGFR by -7.9 mL/min (95% confidence interval [CI] -11.1 to -4.7; P < 0.001), estimated ECV by -192.5 mL (95% CI -318.0 to -66.9; P = 0.003) and estimated PV by -128.9 mL (95% CI -218.0 to 39.8; P = 0.005) at Week 13. CONCLUSIONS: Treatment with empagliflozin for 13 weeks reduced mGFR, estimated ECV and estimated PV in patients with T2D and high risk of cardiovascular events.

Mathematics of apheresis.

Mathematics is related to apheresis medicine. The safety of donor and patient in taking blood components is utterly important. Knowledge of total blood and plasma volume is needed and have to be calculated. By increasing quality, the safety of not only the donor and patient, but also the operator will increase, as well as the efficiency of operating an apheresis collection facility. Various concepts, formulas and calculations methods and their significance in apheresis are given in this paper.

Membrane-based therapeutic plasma exchange: Proposed techniques for preventing filter failure.

BACKGROUND AND OBJECTIVES: Therapeutic plasma exchange (TPE) is commonly performed using membrane-based TPE (mTPE) and is prone to filter failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We report on 46 patients, with a total of 321 mTPE treatments using the NxStage machine. This was a retrospective study with an aim to evaluate the effect of heparin, pre-filter saline dilution and the impact of total plasma volume exchanged (< 3 L vs. ≥3 L) on the rate of filter failure. Primary outcome was the overall rate of filter failure. Secondary outcomes included factors that may have indirectly influenced the rate of filter failure, including hematocrit, platelet count, replacement fluid (Fresh Frozen Plasma vs. albumin), and access type. RESULTS: We found that treatments that received both pre-filter heparin and saline had a statistically significant decrease in filter failure rate as compared to those that received neither (28.6% vs. 5.3%, P = .001), and compared to the treatments that received pre-filter heparin alone (14.2% vs. 5.3%, P = .015). In treatments that received both pre-filter heparin and saline predilution, we noted a significantly higher filter failure rate when the plasma volume exchanged was ≥3 L as compared to those that had <3 L exchanged (12.2% vs. 0.9%, P = .001). CONCLUSIONS: Rate of filter failure in mTPE can be reduced by implementing several therapeutic interventions including pre-filter heparin and pre-filter saline solution. These interventions were not associated with any clinically significant adverse events. Despite the above-mentioned interventions, large plasma volume exchanges of ≥3 L can negatively impact filter life.

The role of plasma volume and fluid overload in the tolerance to ultrafiltration and hypotension in hemodialysis patients.

INTRODUCTION: Ultrafiltration (UF) in hemodialysis (HD) patients is accompanied by irregular falls in plasma volume (PV) and blood pressure (BP). METHODS: We obtained in 321 patients (large cohort), body weight (BW), BP, samples of blood to determine hemoglobin (Hb) and hematocrit (Ht), Pre and Post HD. We estimated the % variation of the PV and its effect on the BP. In a small cohort of 38/321 patients, arterial blood was drawn Pre and Post HD and at 2, 48, and 72 h to determined Hb and Ht and % variation of the PV. Bio-impedance spectroscopy (BIS) was performed, in the same times, to estimate: dry weight (DW), total body water (TBW), extracellular water (ECW), Fluid overload (FO) and phase angle (PhA). RESULTS: We divided our large cohort in two groups. The Hypotensive group with a fall equal or more than 20 mmHg (96/321,30%) and Normotensive group with a drop equal or less than 19 mmHg (225/321,70%). The UF was 2.73 ± 0.72 L in the Hypotensive group and 2.53 ± 0.85 L in the Normotensive group (p < 0.0001). The % PV was -11.7 ± 17.8 in the Hypotensive group and -8.53 ± 10.07 in the Normotensive group (p < 0.0001). The systolic blood pressure (SBP) correlated with the % change of the PV (r = -0.232; p < 0.0001). The FO was contrasted with the % of water removed by UF (r = -0.890; p < 0.0001). CONCLUSION: The SBP drop was secondary to the fall in the PV after UF. The FO was irregular and modulates in part the fall in the SBP.

Increased spleen volume provoked by temperate head-out-of-water immersion.

This study tested the hypotheses that 1) spleen volume increases during head-out-of-water immersion (HOWI) and returns to pre-HOWI values postdiuresis, and 2) the magnitude of apnea-induced spleen contraction increases when preapnea spleen volume is elevated. Spleen volume was measured before and after a set of five apneas in 12 healthy adults (28 ± 5 yr, 3 females) before, during (at 30 and 150 min), and 20 min after temperate temperature (36 ± 1°C) HOWI. At each time point, spleen length, width, and thickness were measured via ultrasound, and spleen volume was calculated using the Pilström equation. Compared with pre-HOWI (276 ± 88 mL), spleen volume was elevated at 30 (353 ± 94 mL, P < 0.01) and 150 (322 ± 87 mL, P < 0.01) min of HOWI but returned to pre-HOWI volume at post-HOWI (281 ± 90 mL, P = 0.58). Spleen volume decreased from pre- to postapnea bouts at each time point (P < 0.01). The magnitude of reduction in spleen volume from pre- to postapneas was elevated at 30 min of HOWI (-69 ± 24 mL) compared with pre-HOWI (-52 ± 20 mL, P = 0.04) but did not differ from pre-HOWI at 150 min of HOWI (-54 ± 16 mL, P = 0.99) and post-HOWI (-50 ± 18 mL, P = 0.87). Thus, spleen volume is increased throughout 180 min of HOWI, and whereas apnea-induced spleen contraction is augmented after 30 min of HOWI, the magnitude of spleen contraction is unaffected by HOWI thereafter.

A crossover control study of three methods of heat acclimation on the magnitude and kinetics of adaptation.

NEW FINDINGS: What is the central question to the study? Are primary indices of heat adaptation (e.g., expansion of plasma volume and reduction in resting core temperature) differentially affected by the three major modes of short-term heat acclimation, that is, exercise in the heat, hot water immersion and sauna? What it the main finding and its importance? The three modes elicited typical adaptations expected with short-term heat acclimation, but these were not significantly different between modes. This comparison has not previously been made and highlights that individuals can expect similar adaptation to heat regardless of the mode used. ABSTRACT: Heat acclimation (HA) can improve heat tolerance and cardiovascular health. The mode of HA potentially impacts the magnitude and time course of adaptations, but almost no comparative data exist. We therefore investigated adaptive responses to three common modes of HA, particularly with respect to plasma volume. Within a crossover repeated-measures design, 13 physically active participants (five female) undertook four, 5-day HA regimes (60 min/day) in randomised order, separated by ≥4 weeks. Rectal temperature (Tre ) was clamped at neutrality via 36.6°C (thermoneutral) water immersion (TWI; i.e., control condition), or raised by 1.5°C via heat stress in 40°C water, sauna (55°C, 52% relative humidity), or exercise in humid heat (40°C, 52% relative humidity; ExH). Adaptation magnitude was assessed as the pooled response across days 4-6, while kinetics was assessed via the 6-day time series. Plasma volume expansion was similar in all heated conditions but only higher than TWI in exercise in the heat (ExH) (by 4%, P = 0.036). Approximately two-thirds of the expansion was attained within the initial 24 h and was moderately related to that present on day 6, regardless of HA mode (r = 0.560-0.887). Expansion was mediated by conservation of both sodium and albumin content, with little evidence for these having differential roles between modes (P = 0.706 and 0.320, respectively). Resting Tre decreased by 0.1-0.3°C in all heated conditions, and systolic blood pressure decreased by 4 mmHg, but not differentially between conditions (P ≥ 0.137). In conclusion, HA mode did not substantially affect the magnitude or rate of adaptation in key resting markers of short-term HA.

Kinetics of 5% and 20% albumin: A controlled crossover trial in volunteers.

BACKGROUND: Albumin for intravenous infusion is marketed in two concentrations, 20% and 5%, but how they compare with regard to plasma volume expansion over time is unclear. METHODS: In a prospective crossover study, 12 volunteers received 3 ml kg-1 of 20% albumin and, on another occasion, 12 ml kg-1 of 5% albumin over 30 min. Hence, equivalent amounts of albumin were given. Blood was collected on 15 occasions over 6 h. Mass balance and volume kinetics were used to estimate the plasma volume expansion and the capillary leakage of albumin and fluid based on measurements of blood hemoglobin, plasma albumin, and the colloid osmotic pressure. RESULTS: The greatest plasma volume expansion was 16.0 ± 6.4% (mean ± SD) with 20% albumin and 19.0 ± 5.2% with 5% albumin (p < .03). The volume expansion with 20% albumin corresponded to twice the infused volume. One third of the 5% albumin volume quickly leaked out of the plasma, probably because of the higher colloid osmotic pressure of the volunteer plasma (mean, 24.5 mmHg) than the albumin solution (19.1 mmHg). At 6 h, the capillary leakage amounted to 42 ± 15% and 47 ± 11% of the administered albumin with the 20% and 5% preparations, respectively (p = .28). The corresponding urine outputs were 547 (316-780) ml and 687 (626-1080) ml (median and interquartile range; p = .24). CONCLUSION: The most important difference between the fluids was a dehydrating effect of 20% albumin when the same albumin mass was administered.

Prognostic Value of Estimated Plasma Volume Status in Patients With Sepsis.

BACKGROUND: In patients with sepsis, timely risk stratification is important to improve prognosis. Although several clinical scoring systems are currently being used to predict the outcome of sepsis, but they all have certain limitations. The objective of this study was to evaluate the prognostic value of estimated plasma volume status (ePVS) in patients admitted to the intensive care unit (ICU) with sepsis or septic shock. METHODS: This single-center, prospective observational study, included 100 patients admitted to the ICU with sepsis or septic shock. Informed consent, blood samples, and co-morbidity data were obtained from the patients on admission, and the severity of sepsis was recorded. The primary outcome was in-hospital mortality and multivariable logistic regression analysis was used to adjust for confounding factors to determine the significant prognostic factor. RESULTS: The in-hospital mortality was 47%. The ePVS was correlated with the amount of total fluids administered 24 hours before the ICU admission. The mean ePVS in patients who died was higher than in those who survived (7.7 ± 2.1 dL/g vs. 6.6 ± 1.6 dL/g, P = 0.003). To evaluate the utility of ePVS in predicting in-hospital mortality, a receiver operating characteristic curve was produced. Sensitivity and specificity were optimal at a cut-off point of 7.09 dL/g, with an area under the curve of 0.655. In the multivariate analysis, higher ePVS was significantly associated with higher in-hospital mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.04-1.85, P = 0.028). The Kaplan-Meier curve showed that an ePVS value above 7.09 was associated with an increased risk of in-hospital mortality compared with the rest of the population (P = 0.004). CONCLUSION: The ePVS was correlated with the amount of intravenous fluid resuscitation and may be used as a simple and novel prognostic factor in patients with sepsis or septic shock who are admitted to the ICU.

Blood volume expansion, normovolemia, and clinical outcomes in chronic human heart failure: more is better.

Expansion in blood volume (BV) is a well-recognized response to arterial underfilling secondary to impaired cardiac output in heart failure (HF). However, the effectiveness of this response in terms of outcomes remains inadequately understood. Prospective analysis was undertaken in 110 patients with HF hospitalized and treated for fluid overload. BVs were measured in a compensated state at the hospital discharge using the indicator-dilution methodology. Data were analyzed for composite 1-year HF-related mortality/first rehospitalization. Despite uniform standard of care, marked heterogeneity in BVs was identified across the cohort. The cohort was stratified by BV expansion greater than or equal to +25% above normal (51% of cohort), mild-moderate expansion (22%), and normal BV (27%). Kaplan-Meier (K-M) survival estimates and regression analyses revealed BV expansion (greater than or equal to +25%) to be associated with better event-free survival relative to normal BV (P = 0.038). Increased red blood cell mass (RBCm; RBC polycythemia) was identified in 43% of the overall cohort and 70% in BV expansion greater than or equal to +25%. K-M analysis demonstrated polycythemia to be associated with better outcomes compared with normal RBCm (P < 0.002). Persistent BV expansion to include RBC polycythemia is common and, importantly, associated with better clinical outcomes compared with normal total BV or normal RBCm in patients with chronic HF. However, compensatory BV expansion is not a uniform physiological response to the insult of HF with marked variability in BV profiles despite uniform standard of care diuretic therapy. Therefore, recognizing the variability in volume regulation pathophysiology has implications not only for impact on clinical outcomes and risk stratification but also potential for informing individualized volume management strategies.NEW & NOTEWORTHY The novel findings of this study demonstrate that intravascular volume profiles among the patients with chronic heart failure (HF) vary substantially even with similar clinical compensation. Importantly, a profile of blood volume (BV) expansion (compared with a normal BV) is associated with lower HF mortality/morbidity. Furthermore, RBC polycythemia is common and independently associated with improved outcomes. These observations support BV expansion with RBC polycythemia as a compensatory mechanism in chronic HF.

Investigating plasma volume expanders as novel macromolecular MRI-CEST contrast agents for tumor contrast-enhanced imaging.

PURPOSE: The aim of this study was to investigate two clinically approved plasma volume expanders (dextran 70 and voluven) as macromolecular MRI-chemical exchange saturation transfer (CEST) contrast agents to assess tumor vascular properties. METHODS: CEST contrast efficiency of both molecules (6% w/v) was measured in vitro at various irradiation saturation powers (1-6 µT for 5 s) and pH values (range, 5.5-7.9) and the exchange rate of hydroxyl protons was calculated. In vivo studies in a murine adenocarcinoma model (n = 4 mice for each contrast agent) upon i.v. injection provided CEST-derived perfusion tumor properties that were compared with those obtained with a gadolinium-based blood-pool agent (Gd-AAZTA-Madec). RESULTS: In vitro measurements showed a marked CEST contrast dependency to pH, with higher CEST contrast at lower pH values for both molecules. The measured prototropic exchange rates confirmed a base-catalyzed exchange rate that was faster for dextran 70 in comparison to voluven. Both molecules showed a similar CEST contrast increase (ΔST% > 3%) in the tumor tissue up to 30 min postinjection, with heterogeneous accumulation. In tumors receiving both CEST and T1 -weighted agents, a voxel-by-voxel analysis indicated moderate spatial correlation of perfusion properties between voluven/dextran 70 and Gd-AAZTA-Madec, suggesting different distribution patterns according to their molecular size. CONCLUSIONS: The obtained results showed that both voluven and dextran 70 can be exploited as MRI-CEST contrast agents for evaluating tumor enhancement properties. Their increased accumulation in tumors and prolonged contrast enhancement promote their use as blood-pool MRI-CEST agents to examine tumor vascularization.

Plasma Volume Status and Its Association With In-Hospital and Postdischarge Outcomes in Decompensated Heart Failure.

BACKGROUND: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial. METHODS AND RESULTS: The KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. There were 6373 (89.2%), and 6354 (89.0%) patients who had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with N-terminal prohormone BNP, and with measures of decongestion such as body weight change and urine output (r < 0.3 for all). Duarte-ePV was trending toward an association with worse 30-day (adjusted odds ratio 1.07, 95% confidence interval [CI] 1.00-1.15, P = .058), but not 180-day outcomes (adjusted hazard ratio 1.03, 95% CI 0.97-1.09, P = .289). A continuous KH-ePVS of >0 (per 10-unit increase) was associated with improved 30-day outcomes (adjusted odds ratio 0.75, 95% CI 0.62-0.91, P = .004). The continuous KH-ePVS was not associated with 180-day outcomes (adjusted hazard ratio 1.05, 95% CI 0.98-1.12, P = .139). CONCLUSIONS: Baseline PV estimates had a weak association with in-hospital measures of decongestion. The Duarte-ePV trended toward an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.

Distribution and morphology of sensory and autonomic fibres in the subendocardial plexus of the rat heart.

Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial volume receptors are mechanically sensitive vagal afferents which relay to the medulla and hypothalamus, affecting vasopressin release and renal sympathetic activity. To date, two anatomically distinct sensory endings have been identified which may subserve cardiac mechanosensation: end-nets and flower-spray endings. To map the distribution of atrial receptors in the subendocardial space, we have double-labelled rat right atrial whole mounts for neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) and generated high-resolution maps of the rat subendocardial neural plexus at the cavo-atrial region. In order to elucidate the nature of these fibres, double labelling with synaptophysin (SYN) and either NFH, calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) was performed. The findings show that subendocardial nerve nets are denser at the superior cavo-atrial junction than the mid-atrial region. Adluminal plexuses had the finest diameters and stained positively for synaptic vesicles (SV2 and SYN), CGRP and TH. These plexuses may represent sympathetic post-ganglionic fibres and/or sensory afferents. The latter are candidate substrates for type B volume receptors which are excited by stretch during atrial filling. Deeper nerve fibres appeared coarser and may be cholinergic (positive staining for ChAT). Flower-spray endings were never observed using immunohistochemistry but were delineated clearly with the intravital stain methylene blue. We suggest that differing nerve fibre structures form the basis by which atrial deformation and hence atrial filling is reflected to the brain.

Effects of 1-year treatment with canagliflozin on body composition and total body water in patients with type 2 diabetes.

AIM: To characterize the long-term changes in body composition associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors. MATERIALS AND METHODS: In this multicentre, single-arm, open-label study, 107 patients with type 2 diabetes were treated with canagliflozin 100 mg, as add-on therapy, for 12 months. Body composition was measured with a body composition analyser (T-SCAN PLUS) using the impedance method to prospectively analyse changes in body components, including percentage of body fat, body fat mass, total body water, muscle mass and mineral mass. Estimated plasma volume (PV) was calculated using the Kaplan formula. RESULTS: Body weight showed a significant decrease from 1 month to 12 months of treatment with canagliflozin, with a higher rate of decrease in body fat in body composition. A significant decrease in mineral mass was also observed, but its rate was low. Following treatment with canagliflozin, changes in total body water did not affect intracellular water, and a significant decrease in extracellular water, including plasma components, was observed early and was sustained up to 12 months. Protein mass, a component of muscle mass, was not affected, with only a slight decrease in water volume observed. CONCLUSIONS: Canagliflozin decreased extracellular fluid and PV in addition to decreasing fat in the body via calorie loss resulting from urinary glucose excretion. This study suggested that SGLT2 inhibitors might reduce body weight by regulating fat mass or water distribution in the body and might have cardiac and renal protective effects by resetting the homeostasis of fluid balance.

Estimated plasma volume status (ePVS) is a predictor for acute myocardial infarction in-hospital mortality: analysis based on MIMIC-III database.

BACKGROUND: Estimated plasma volume status (ePVS) has been reported that associated with poor prognosis in heart failure patients. However, no researchinvestigated the association of ePVS and prognosis in patients with acute myocardial infarction (AMI). Therefore, we aimed to determine the association between ePVS and in-hospital mortality in AMI patients. METHODS AND RESULTS: We extracted AMI patients data from MIMIC-III database. A generalized additive model and logistic regression model were used to demonstrate the association between ePVS levels and in-hospital mortality in AMI patients. Kaplan-Meier survival analysis was used to pooled the in-hospital mortality between the various group. ROC curve analysis were used to assessed the discrimination of ePVS for predicting in-hospital mortality. 1534 eligible subjects (1004 males and 530 females) with an average age of 67.36 ± 0.36 years old were included in our study finally. 136 patients (73 males and 63 females) died in hospital, with the prevalence of in-hospital mortality was 8.9%. The result of the Kaplan-Meier analysis showed that the high-ePVS group (ePVS ≥ 5.28 mL/g) had significant lower survival possibility in-hospital admission compared with the low-ePVS group (ePVS < 5.28 mL/g). In the unadjusted model, high-level of ePVS was associated with higher OR (1.09; 95% CI 1.06-1.12; P < 0.001) compared with low-level of ePVS. After adjusted the vital signs data, laboratory data, and treatment, high-level of ePVS were also associated with increased OR of in-hospital mortality, 1.06 (95% CI 1.03-1.09; P < 0.001), 1.05 (95% CI 1.01-1.08; P = 0.009), 1.04 (95% CI 1.01-1.07; P = 0.023), respectively. The ROC curve indicated that ePVS has acceptable discrimination for predicting in-hospital mortality. The AUC value was found to be 0.667 (95% CI 0.653-0.681). CONCLUSION: Higher ePVS values, calculated simply from Duarte's formula (based on hemoglobin/hematocrit) was associated with poor prognosis in AMI patients. EPVS is a predictor for predicting in-hospital mortality of AMI, and could help refine risk stratification.

Impact of plasma volume status on mortality following left ventricular assist device implantation.

Worsening systemic congestion is often the central trigger of hospitalization in patients with heart failure. However, accurate assessment of congestion is challenging. The prognostic impact of systemic congestion following durable continuous-flow left ventricular assist device (LVAD) implantation remains unknown. Consecutive patients who received durable continuous-flow LVAD implantation between January 2014 and June 2017 and were followed for 1 year were included. The association of preoperative plasma volume status, which was calculated using patients' body weight and hematocrit and expressed as a deviation from ideal plasma volume, with 1-year mortality following LVAD implantation was investigated. In total, 186 patients (median 57 years and 138 males) were included. Baseline plasma volume status was -30.1% (-37.1%, -19.4%) on median. Eighty-eight patients (47%) had higher plasma volume status (>-29.8%), and their 1-year survival was significantly lower than those without (67% vs. 87%, P = .001). High plasma volume status was an independent predictor of 1-year death with an adjusted hazard ratio of 4.52 (95% confidence interval 1.52-13.5). Baseline systemic congestion, as defined by the high plasma volume status, was associated with higher mortality following durable continuous-flow LVAD implantation. The implication of improving preoperative plasma volume remains an area of needed investigation.