Plasma Volume Expansion Research Articles

Pro: The Role of Albumin in Pre-Liver Transplant Management.

The wait-list mortality of patients with decompensated cirrhosis awaiting liver transplantation remains elevated due to the occurrence of complications. Etiologic treatments improve patient survival and lower the incidence of complications when applied in compensated cirrhosis, but a decompensated disease does not improve or even progress despite a response to therapy in a substantial number of patients. Thus, disease-modifying treatments that reduce the incidence of complications and improve survival are most needed. Such treatments should be able to counteract one or possibly more pathophysiological mechanisms and thus lead to the proinflammatory and pro-oxidant milieu that characterizes decompensated cirrhosis. In this respect, albumin represents a potentially ideal agent. In fact, besides its ability to expand plasma volume, albumin possesses nononcotic properties, exerting potent antioxidant and immune-modulating effects. Recent studies have assessed the effect of longterm albumin administration in decompensated cirrhosis. Although the results of these studies may appear conflicting, their analyses suggest that albumin, if given in a sufficient amount and for a sufficient duration, can significantly reduce the incidence of life-threatening complications of cirrhosis and patient mortality. For these reasons, we favor albumin administration to patients with decompensated cirrhosis wait-listed for liver transplantation.

Do Pre-Hemodialysis Estimates of Extracellular Volume Excess Using Bioimpedance and N-Terminal Brain Natriuretic Peptide Correlate With Cardiac Chamber Size Measured by Magnetic Resonance Imaging?

Bioimpedance can be used to measure extracellular water (ECW) and total body water in hemodialysis (HD) patients and estimate ECW excess. However, ECW excess potentially includes both an increase in the plasma volume and also the extravascular volume. Overestimating the amount of fluid to be removed during HD risks intra-dialytic hypotension. We wished to determine the association between estimates of ECW excess comparing several different equations using bioimpedance, brain N-terminal pro-brain natriuretic peptide (NT-proBNP) with cardiac chamber volumes and function as determined by cardiac magnetic resonance imaging pre-HD measurements of ECW and total body water were made using multifrequency bioimpedance and cardiac chamber sizes and function were determined by magnetic resonance imaging. Thirty patients, 20 males (66.7%), mean age 64.4 ± 15.3 years were studied. ECW and ECW/height were positively associated with indexed right ventricular end-systolic (RVESVi) and end-diastolic volume (RVEDVi) (RVESi r = 0.46, r = 0.43; RVEDi r = 0.50, r = 0.44, all P < 0.05), but not with left sided cardiac volumes. Whereas NT-proBNP was associated with indexed left atrial and ventricular size (r = 0.47, r = 0.58, P < 0.05), but not right sided cardiac volumes. Pre-HD NT-proBNP was associated with left sided cardiac chamber sizes, but not with right sided chamber sizes, whereas ECW/height was associated with right sided cardiac chamber sizes. As right-sided cardiac chamber size is more responsive to and reflective of changes in intravascular volume than the left atrium and ventricle, then bioimpedance measured ECW is potentially more reliable in estimating plasma volume expansion.

The conundrum of patients with obesity, exercise intolerance, elevated ventricular filling pressures and a measured ejection fraction in the normal range.

Patients with obesity, a reduced exercise capacity, increased cardiac filling pressures and a measured left ventricular ejection fraction in the normal range do not have a homogeneous disorder, but instead, exhibit one of three phenotypes. First, many obese people exhibit sodium retention, plasma volume expansion and cardiac enlargement, and some are likely to have heart failure that is related to hypervolaemia, even though cardiac index and circulating levels of natriuretic peptides are not meaningfully increased. Second, in some middle-aged men and women (particularly those with minimal co-morbidities), levels of natriuretic peptides increase markedly and can lower systemic vascular resistance, thus leading to high-output heart failure (HOHF) and glomerular hyperfiltration. Third, older obese people, particularly women with multiple co-morbidities, exhibit the syndrome of heart failure with a preserved ejection fraction (HFpEF). Despite degrees of plasma volume expansion similar to HOHF, these patients exhibit only modestly increased ventricular dimensions and circulating levels of natriuretic peptides (despite a high prevalence of atrial fibrillation), and glomerular function is characteristically impaired. A conceptual framework is proposed to distinguish among the three phenotypes seen in obese patients with exercise intolerance, increased ventricular filling pressures and a measured left ventricular ejection fraction in the normal range, since they may respond differently to therapeutic interventions. Efforts are needed to enhance the recognition of heart failure in obese people and to ensure that clinical trials that are designed to study patients with HFpEF actually enrol those who have the disease.

The first domestic devices for intraosseous infusion - is the great advance of military medicine in pre-hospital stage enhancement

Traumatic shock is considered to be the most common clinical form of a severe patient’s condition (63%). Timely and adequate blood volume resuscitation is one of the most important procedures in providing medical care to critically injured casualties and patients at the forward medical evacuation stage. The key to this problem, especially when the infusion therapy is needed at the pre-hospital stage, is the development of alternative (extravascular) techniques of plasma volume expander administration. The article presents the results of testing of the first domestic medical devices for intraosseous infusion in critically injured casualties and patients. At present, on commission of the Russian Ministry of Defense and with the scientific support of Kirov Military Medical Academy, domestic enterprises developed test samples of medical devices to provide intraosseous infusions: a «Disposable device for intraosseous infusion of solutions if there is no intravenous access, which was designed on the basis of a spring drive» - the index «VKI-P», developed by limited liability company «Novoplast-М» and a set for intraosseous infusion using an electric drive - the index « VKI-E», developed by limited liability company «Research engineering company «Spetsproekt». Assessment of performance of test samples of the medical devices for intraosseous infusions «VKI-P» and «VKI-E» was carried out using pathophysiologic model of traumatic shock in 14 experimental animals (pigs) by creating artificial blood loss of medium severity, 25% of circulating blood volume (in average 440 ml), followed by its resuscitation with intraosseous infusion of 0,9% solution of NaCl. As a result of the performed tests it was found that the device «VKI-P» and the set «VKI-E» provide for NaCl infusion in major vessels (with an intraosseous infusion), 750 ml of volume during 45-50 min, and can be used as an alternative access to provide infusion as a part of anti-shock therapy, which solves the problem of volume resuscitation when giving care to severely injured casualties and patients at the forward medical evacuation stages. These samples may be recommended for inclusion into the medical service list of complete supplies and the Medical Corps supply support, the Armed Forces of the Russian Federation.

The Optimal Plasma Volume Status in Heart Failure in Relation to Clinical Outcome

Progressive plasma volume (PV) expansion is a hallmark of chronic heart failure (HF), ultimately contributing to decompensated heart failure. Monitoring PV might offer prognostic information and might be a target for tailored therapy. The correlation between technetium-99 (99Tc)-labeled red blood cell measured PV and calculated PV was first determined in a validation cohort. The relationship between PV status (PVS; a marker how much actual PV deviated from the ideal PV) and outcome was analyzed with the use of Cox proportional modeling in a prospective chronic HF (CHF) population (the outcome cohort). Thirty-one HF patients were included in the validation cohort. Calculated PV correlated well with 99Tc-measured PV (r = 0.714; P = .001). A total of 1173 patients (HF with reduced ejection fraction [HFrEF]: n = 872; HF with mid-range EF [HFmrEF]: n = 229; HF with preserved EF [HFpEF]: n = 72) were prospectively included in the outcome cohort. The mean PVS in the outcome cohort was -6.7% ± 10%, indicating slight PV contraction. Higher PVS was independently associated with increased risk for HF hospitalization and all-cause mortality (hazard ratio 1.016; 95% confidence interval 1.006-1.027 per 1% increase in PVS; P = .002). Receiver operating characteristic curve analysis indicated that a PVS of -6.5% optimally predicted absence of adverse outcome. Hazard ratio analysis indicated that CHF patients were less equipped in tolerating PV expansion in comparison to PV contraction. The use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and mineralocorticoid receptor antagonists were independently associated with a higher odds of having an optimal PVS in HFrEF and HFmrEF (all P < .05), but not in HFpEF. Calculated PV correlates well with measured PV in HF patients. An increase in PV is independently associated with a higher risk of adverse outcome, and a slight contraction of the predicted PV seems to be related to less adverse events. Higher dosages of renin-angiotensin-aldosterone blockers are associated with higher odds of having an optimal PV status.

Once- and twice-daily heat acclimation confer similar heat adaptations, inflammatory responses and exercise tolerance improvements.

This experiment aimed to investigate the efficacy of twice‐daily, nonconsecutive heat acclimation (TDHA) in comparison to once‐daily heat acclimation (ODHA) and work matched once‐ or twice‐daily temperate exercise (ODTEMP, TDTEMP) for inducing heat adaptations, improved exercise tolerance, and cytokine (immune) responses. Forty males, matched biophysically and for aerobic capacity, were assigned to ODHA, TDHA, ODTEMP, or TDTEMP. Participants completed a cycling‐graded exercise test, heat acclimation state test, and a time to task failure (TTTF) at 80% peak power output in temperate (TTTFTEMP: 22°C/40% RH) and hot conditions (TTTFHOT: 38°C/20% RH), before and after 10‐sessions (60 min of cycling at ~2 W·kg−1) in 45°C/20% RH (ODHA and TDHA) or 22°C/40% RH (ODTEMP or TDTEMP). Plasma IL‐6, TNF‐α, and cortisol were measured pre‐ and postsessions 1, 5, and 10. ODHA and TDHA induced equivalent heat adaptations (P < 0.05) (resting rectal temperature [−0.28 ± 0.22, −0.28 ± 0.19°C], heart rate [−10 ± 3, −10 ± 4 b·min−1], and plasma volume expansion [+10.1 ± 5.6, +8.5 ± 3.1%]) and improved heat acclimation state (sweat set point [−0.22 ± 0.18, −0.22 ± 0.14°C] and gain [+0.14 ± 0.10, +0.15 ± 0.07 g·sec−1·°C−1]). TTTFHOT increased (P < 0.001) following ODHA (+25 ± 4%) and TDHA (+24 ± 10%), but not ODTEMP (+5 ± 14%) or TDTEMP (+5 ± 17%). TTTFTEMP did not improve (P > 0.05) following ODHA (+14 ± 4%), TDHA (14 ± 8%), ODTEMP (9 ± 10%) or TDTEMP (8 ± 13%). Acute (P < 0.05) but no chronic (P > 0.05) increases were observed in IL‐6, TNF‐α, or cortisol during ODHA and TDHA, or ODTEMP and TDTEMP. Once‐ and twice‐daily heat acclimation conferred similar magnitudes of heat adaptation and exercise tolerance improvements, without differentially altering immune function, thus nonconsecutive TDHA provides an effective, logistically flexible method of HA, benefitting individuals preparing for exercise‐heat stress.

Néphrotoxicité des produits de remplissage

Expansion of extracellular volume is a treatment traditionally proposed to correct abnormalities of renal perfusion and prevent ischemic injury. However, vascular filling is not at risk for tissue oxygenation and renal function. The use of synthetic colloids exposes the patient to the risk of developing lesions such as osmotic nephrosis. Hyperoncotic colloids reduce glomerular filtration pressure. The nephrotoxicity of hydroxyethyl starches is now clearly established regardless of their characteristics. Colloids have never demonstrated their superiority as plasma volume expanders, they should be abandoned in favour of crystalloid solutions.

Sorption of 223Ra and 211Pb on modified nanodiamonds for potential application in radiotherapy

223Ra and 211Pb/211Bi radionuclides with radiochemical purity were obtained from 227Ac/223Ra generator on DGA resin. Covalent grafting of organic complexons (ethylenediaminetetraacetic acid—EDTA and derivatives of amino acids—L1 and L2 to aminated nanodiamonds (ND) was performed by carbodiimide method. Adsorption behavior of Ra and Pb in plasma volume expander on modified nanodiamonds was studied in detail. Effective adsorption have been found for 211Pb in physiologically acceptable conditions. Sorption behavior of generator radionuclides 223Ra and 211Pb on the surface of ND-L1 and ND-L2 in aqueous solution (pH = 6.3) was studied. It was shown that the labeling yield of 211Pb from the solution was about 94%. The sorption of 223Ra under the same conditions was weak. The sorption/desorption kinetics of 211Pb on the surface of ND-EDTA in the plasma volume expander was studied. The desorption rate of 211Pb did not exceed 2.5% within 60 min (pH 7.2–7.4).

Don't stop at the top: plasma volume expansion and pulmonary vasodilatation restore left ventricular function at rest but not during exercise at high altitude.

Don't stop at the top: plasma volume expansion and pulmonary vasodilatation restore left ventricular function at rest but not during exercise at high altitude.

(Pro)renin receptor contributes to pregnancy-induced sodium-water retention in rats via activation of intrarenal RAAS and α-ENaC.

The (pro)renin receptor (PRR) is a new component of the renin-angiotensin-aldosterone system (RAAS) and regulates renin activity. The objective of the present study was to test potential roles of the renal PRR and intrarenal RAAS in the physiological status of late pregnancy. Late pregnant Sprague-Dawley rats were studied 19-21 days after sperm was observed in vaginal smears. Experiments were performed using age-matched virgin rats and late pregnant rats treated with the specific PRR inhibitor PRO20 (700 μg·kg-1·day-1 sc for 14 days, 3 times/day for every 8 h) or vehicle. The indices of RAAS, including PRR, renin, angiotensin II, and aldosterone levels, were examined by immunoblotting, qRT-PCR, or ELISA. Further analyses of renal epithelial sodium channel (ENaC) expression, sodium-water retention, and plasma volume were performed. We first present evidence for the activation of intrarenal RAAS in late pregnant rats, including increases in urinary renin activity, active and total renin content, and prorenin content, angiotensin II and aldosterone excretion, in parallel with increased renal PRR expression and urinary soluble PRR excretion. Functional evidence demonstrated that PRR antagonism with PRO20 effectively suppressed the indices of intrarenal RAAS in late pregnant rats. In addition, our results revealed that renal α-ENaC expression, sodium-water retention, and plasma volume were elevated during late pregnancy, which were all attenuated by PRO20. In summary, the present study examined the renal mechanism of sodium-water retention and plasma volume expansion in late pregnant rats and identified a novel role of PRR in regulation of intrarenal RAAS and α-ENaC and thus sodium and fluid retention associated with pregnancy.

Heart Failure Outcomes With Volume-Guided Management

ObjectivesThis study performed a retrospective outcome analyses of a large cohort of mixed ejection fraction patients admitted for acute heart failure (HF), whose inpatient care was guided by individual quantitative blood volume analysis (BVA) results. BackgroundDecongestion strategies in patients hospitalized for HF are based on clinical assessment of volume and have not integrated a quantitative intravascular volume metric. MethodsPropensity score control matching analysis was performed in 245 consecutive HF admissions to a community hospital (September 2007 to April 2014; 78 ± 10 years of age; 50% with HF with reduced ejection fraction [HFrEF]; and 30% with Stage 4 chronic kidney disease). Total blood volume (TBV), red blood cell volume (RBCV), and plasma volume (PV) were measured at admission by using iodine-131-labeled albumin indicator-dilution technique. Decongestion strategy targeted a TBV threshold of 6% to 8% above patient-specific normative values. Anemia was treated based on cause. Hematocrit (Hct) measurements were monitored to assess effectiveness of interventions. Control subjects derived from Centers for Medicare and Medicaid Services data were matched 10:1 for demographics, comorbidity, and year of treatment. ResultsAlthough 66% of subjects had PV expansion, only 37% were hypervolemic (TBV >10% excess). True anemia (RBCV ≥10% deficit) was present in 62% of subjects. Treatment of true anemia without hypervolemia resulted in a rise in peripheral Hct of 2.7 ± 2.9% (p < 0.001), and diuretic treatment of hypervolemia in cases without anemia caused a 4.5 ± 3.9% (p < 0.001) increase in peripheral Hct at 11.3 ± 7.5 days after admission. Subjects had lower 30-day rates of readmission (12.2% vs. 27.7%, respectively; p < 0.001), of 30-day mortality (2.0% vs. 11.1%, respectively; p < 0.001), and of 365-day mortality (4.9% vs. 35.5%, respectively; p < 0.001) but longer lengths of stay (7.3 vs. 5.6 days, respectively; p < 0.001) than control subjects. ConclusionsRetrospective outcomes using volume-guided HF therapy versus propensity-matched controls support the benefit of BVA in guiding volume management and reducing death and rehospitalization due to HF.

Efficacy of Hot Yoga as a Heat Stress Technique for Enhancing Plasma Volume and Cardiovascular Performance in Elite Female Field Hockey Players.

Perrotta, AS, White, MD, Koehle, MS, Taunton, JE, and Warburton, DER. Efficacy of hot yoga as a heat stress technique for enhancing plasma volume and cardiovascular performance in elite female field hockey players. J Strength Cond Res 32(10): 2878-2887, 2018-This investigation examined the efficacy of hot yoga as an alternative heat stress technique for enhancing plasma volume percentage (PV%) and cardiovascular performance. Ten international caliber female field hockey players completed six 60-minute hot yoga sessions using permissive dehydration over 6 days, followed by a 6-day national team camp. Changes in PV% were examined throughout the intervention and postintervention period. A graded maximal exercise test was performed in a thermoneutral environment (23.2 ± 1.0° C) 24 hours before and 24 hours after intervention. Six days of hot yoga initiated a moderate state of hypovolemia (PV% = -3.5%, 90% confidence limit [CL] [-6.9 to -0.13]), trivial improvements in maximal aerobic power (V[Combining Dot Above]O2max) (effect size [ES] = 0.06, 90% CL [-0.16 to 0.28]), and run time to exhaustion (ES = 0.11, 90% CL [-0.07 to 0.29]). Small meaningful improvements were observed in running speed (km·h) at ventilatory threshold (VT1) (ES = 0.34, 90% CL [-0.08 to 0.76]), VT2 (ES = 0.53, 90% CL [-0.05 to 1.1]), along with adaptations in the respiratory exchange ratio during high-intensity exercise (ES = -0.25, 90% CL [-0.62 to 0.12]). A large plasma volume expansion transpired 72 hours after intervention (PV% = 5.0%, 90% CL [1.3-8.7]) that contracted to a small expansion after 6 days (PV% = 1.6%, 90% CL [-1.0 to 4.2]). This investigation provides practitioners an alternative heat stress technique conducive for team sport, involving minimal exercise stress that can preserve maximal cardiovascular performance over periodized rest weeks within the yearly training plan. Furthermore, improvements in submaximal performance and a delayed hypervolemic response may provide a performance-enhancing effect when entering a 6-day competition period.

430. Omics technologies and the future of preeclampsia research and clinical practice

Despite the obvious success of human reproduction, pregnancy and childbirth pose significant risk to maternal and infant health. The great obstetrical syndromes have been a scourge for pregnant women and their care-givers continuing to the present day. Our understanding of the aetiology of these syndromes including preeclampsia is incomplete largely due to the fact that there are multiple pathways involved in their pathogenesis. For preeclampsia genetic, nutritional and other environmental factors have been implicated mostly those associated with inflammation, a skewed immune response to ’foreign’ fetal (paternal) antigens, control of blood pressure and plasma volume expansion, thrombosis, metabolic health, insulin resistance and placental trophoblast invasion and colonization of the uterine spiral arterioles. The challenge is to understand how all of these interact to cause disease. And to determine what to measure to predict risk not just for early onset preeclampsia but also for the much more common but still potentially life threatening preeclampsia at term. The cross talk between fetus, placenta and mother provides clues for new approaches for risk prediction, diagnosis and treatment. Integration of twenty first century omics interrogation of the placenta and maternal blood across gestation may provide tools with which to identify and monitor women and fetuses at risk and permit early intervention and treatments. Casting the net as broadly as possible enables unbiased identification of novel markers of impending disease. It will likely also inform subsequent diagnostics and treatments. But let’s not confine our thinking to one prognostic profile per pregnancy complication. Preeclampsia may be considered to be 2 or more disorders (early onset and term) with different molecular antecedent profiles and potentially different prevention strategies.

151. Aldosterone as independent predictor of placental and birth weights: Odense Child Cohort study

Introduction Aldosterone is involved in plasma volume expansion and its levels, along with the levels of other members of the renin-angiotensin-aldosterone system (RAAS), are increased in healthy pregnancy. Aldosterone appears to contribute to an optimal fetal development by enhancing placental growth factor (PlGF) expression and trophoblast cell proliferation. In contrast to normal pregnancy, aldosterone is suppressed in preeclampsia. Hypothesis Aldosterone independently contributes to placental and fetal growth. Methods The project is based on data from the Odense Child Cohort, a prospective population-based study from the Municipality of Odense, Denmark, currently with 2500 active families. The participants were recruited between 2010 and 2012. To analyze plasma aldosterone levels and urinary aldosterone excretion (UAldoV), we used a subsample of 637 urine samples (24-h collections) from gestational week 28. Plasma aldosterone and UAldoV were determined by a commercially available ELISA. Predictive values of aldosterone were assessed by multiple regression analysis. Primary outcomes were placental weight (PW) and gestational age-adjusted birth weight Z-score (BW sds). Results UAldoV, but not plasma aldosterone concentration, independently contributed to PW and BW sds (adjusted β coefficients ± SEM: 3.21 ± 1.51, p Discussion At 28 weeks of gestation, 24-h urinary aldosterone excretion was an independent predictor of placental and birth weights. In perspective, aldosterone could be a candidate biomarker for future screening and monitoring programs of high-risk pregnancies. Our findings support the physiological role for aldosterone and likely NaCl conservation for normal pregnancy. Mineralocorticoid supplementation could be considered for pregnancies with high risk for IUGR in order to achieve elevated levels of mineralocorticoids and thus benefit placental and fetal development.

Approach and management of dysnatremias in cirrhosis.

Hypervolemic (dilutional) hyponatremia is the most common dysnatremia in cirrhosis, with a prevalence close to 50% in patients with ascites, while hypovolemic hyponatremia occurs in a minority of cases. Hyponatremia carries a poor prognosis, being associated with increased mortality and reduced survival after liver transplantation. Hypernatremia is rarer and is also associated with an adverse prognosis. Increased non-osmotic secretion of arginine vasopressin and altered renal tubular sodium handling due to impaired free water generation are the mechanisms leading to hypervolemic hyponatremia, while diuretic-induced fluid loss is the main cause of hypovolemic hyponatremia. Hypernatremia usually follows hypotonic fluid losses due to osmotic diuresis (glycosuria) or lactulose-induced diarrhea. The main clinical manifestations of dysnatremias are due to their effects on the central nervous system: astroglial cell hyperhydration follows hyponatremia-an abnormality that exacerbates ammonia neurotoxicity-while the opposite abnormality occurs with hypernatremia. Asymptomatic or mildly symptomatic hypervolemic hyponatremia is mainly managed by correcting of precipitating factors and non-osmotic fluid restriction. Severe, life-threatening hyponatremia requires hypertonic saline infusion, avoiding rapid and complete correction of serum sodium concentration to prevent neurological sequelae such as osmotic demyelination. V2 receptor blockade by vaptans may be considered in patients with sustained hyponatremia waitlisted for liver transplantation. Diuretic withdrawal and plasma volume expansion are required in hypovolemic hypernatremia. Prompt recognition, removal of the precipitating factor(s) and non-osmotic fluid administration represent the mainstays of hypernatremia management. Rapid correction of long-standing hypernatremia can lead to cerebral edema and has to be avoided.

Comparison of dextran and albumin on blood coagulation in patients undergoing major gynaecological surgery

BackgroundHydroxyethyl starches have been withdrawn from the European market. In Sweden, dextran was the main colloid until 2000, when starches overtook the market. After the recent 6S-trial, it was suggested that dextran could be reinstituted, but concerns for greater coagulopathy, bleeding and anaphylaxis still remain. An experimental study from our department indicated that isovolemic substitution of dextran-70 did not derange the von Willebrand function more than albumin 5%, considering the fact that dextran is hyperoncotic in comparison to albumin 5% and, therefore, induces a greater plasma volume expansion and thereby a greater dilutional coagulopathy.MethodsEighteen patients undergoing major gynaecological surgery were assigned to receive either 5% albumin or 6% dextran-70 with 9 patients in each group. Standard coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and platelet count, viscoelastic coagulation test thromboelastometry (ROTEM) and the Multiplate platelet aggregation test were used to test for coagulation defects at different time points perioperatively. Blood loss, blood loss replacement data and haemodynamic parameters were retrieved from anaesthetic and postoperative charts. A local departmental fluid and transfusion/infusion protocol assured haemoglobin > 90 g/l and mean arterial pressure > 65 mmHg with Ringer’s acetate in addition to the colloid use.ResultsThere were no differences in demographic data between the groups. The tissue factor-activated (EXTEM) clot-structure parameter ROTEM A10 was decreased significantly in the dextran group as compared to the albumin group after the infusion of 500 ml of either colloid solution. The PT and aPTT were significantly prolonged, and the platelet count decreased postoperatively in the dextran group, whereas albumin only deranged fibrinogen levels as compared to preoperative levels. There were no differences in Multiplate platelet aggregometry, amount of haemorrhage or transfusion of blood components between the groups.ConclusionsStandard plasma-based coagulation tests, platelet count and whole blood viscoelastic clot structure are affected by 6% dextran-70 to a greater extent than by 5% albumin, but platelet aggregation is not. Future studies should use more advanced haemodynamic monitoring to assess isovolemic plasma volume expansion with dextran and whether this affects haemostasis to a lesser degree.

Adaptive remodeling of renal Na+ and K+ transport during pregnancy.

Renal ion transport undergoes dramatic changes during the course of gestation. These adaptations are necessary to meet the dynamic requirements of pregnancy and support fetal development. Pregnancy is characterized by a high demand for both sodium and potassium. Recently there has been work in the field profiling the modifications of the renal tubules in pregnancy to meet these demands. The purpose of this review is to summarize these findings. The work to date suggests an important role for the distal nephron in both the renal sodium and potassium reabsorption during pregnancy. There is strong evidence that renal sodium reabsorption is mediated by the epithelial sodium channel (ENaC). Whereas renal potassium reabsorption is mediated by upregulation of potassium retaining transporters (HKA2) and downregulation of potassium secreting channels (ROMK, BK). Fetal growth restriction and hypertensive disorders of pregnancy including preeclampsia are marked by suboptimal maternal plasma volume expansion, which is determined by renal electrolyte handling. Therefore, understanding the physiologic demand for sodium and potassium in pregnancy and the adaptations required to support these needs is necessary for the effective treatment of diseased states of pregnancy.

Volume-Kidney Interaction in Chronic Heart Failure - Impact of Subclinical Volume Expansion and Chronic Kidney Disease on Clinical Outcomes

ObjectivesAssess the impact of volume-kidney interactions on outcomes in clinically “euvolemic” chronic heart failure (HF) patients with co-existing chronic kidney disease (CKD).BackgroundCardio-renal interactions are complex and bi-directional and may in part be mediated by the extent of intravascular volume overload. The impact of subclinical volume expansion on outcomes in HF patients with CKD has not been previously examined.MethodsPlasma volume (PV) was prospectively measured in 110 stable HF patients with varying degrees of CKD using a standardized radiolabeled albumin indicator-dilution technique. To examine the interactive roles of volume expansion and CKD the cohort was dichotomized by median PV and then further stratified by cohort median creatinine (sCr), eGFR, and BUN and analyzed for outcomes of HF-related mortality or 1st hospitalization using Kaplan-Meier method.ResultsSubclinical volume overload was demonstrated in 76% of the cohort. Over 1.5 years, sCr and BUN above and eGFR below (Fig.) cohort median values identified highest risk for the composite end-point but only in severe PV expansion (≥ median expansion of +26%) (p=0.02). In normal to moderate PV expansion (< +26% expansion) worse renal function was not associated with increased risk (p=0.578).ConclusionsIn clinically stable chronic HF patients with co-existing CKD, subclinical PV expansion is common, and importantly the extent of PV expansion impacts outcomes including early HF mortality. However, better kidney function mitigates the deleterious effects of severe PV expansion, while mild-moderate expansion balances the risks of worse renal function. Thus, volume-kidney interactions are complex with volume status modulating the impact of CKD on outcomes in chronic HF. Figures. Risk Stratification by Median eGFR in Chronic Heart Failure Patients with A. Severe Plasma Volume Expansion (PV ≥ Median of +26% Above Normal Volume) B. Mild-Moderate Plasma Volume Expansion (PV < Median of +26% Above Normal Volume) Assess the impact of volume-kidney interactions on outcomes in clinically “euvolemic” chronic heart failure (HF) patients with co-existing chronic kidney disease (CKD). Cardio-renal interactions are complex and bi-directional and may in part be mediated by the extent of intravascular volume overload. The impact of subclinical volume expansion on outcomes in HF patients with CKD has not been previously examined. Plasma volume (PV) was prospectively measured in 110 stable HF patients with varying degrees of CKD using a standardized radiolabeled albumin indicator-dilution technique. To examine the interactive roles of volume expansion and CKD the cohort was dichotomized by median PV and then further stratified by cohort median creatinine (sCr), eGFR, and BUN and analyzed for outcomes of HF-related mortality or 1st hospitalization using Kaplan-Meier method. Subclinical volume overload was demonstrated in 76% of the cohort. Over 1.5 years, sCr and BUN above and eGFR below (Fig.) cohort median values identified highest risk for the composite end-point but only in severe PV expansion (≥ median expansion of +26%) (p=0.02). In normal to moderate PV expansion (< +26% expansion) worse renal function was not associated with increased risk (p=0.578). In clinically stable chronic HF patients with co-existing CKD, subclinical PV expansion is common, and importantly the extent of PV expansion impacts outcomes including early HF mortality. However, better kidney function mitigates the deleterious effects of severe PV expansion, while mild-moderate expansion balances the risks of worse renal function. Thus, volume-kidney interactions are complex with volume status modulating the impact of CKD on outcomes in chronic HF. Figures. Risk Stratification by Median eGFR in Chronic Heart Failure Patients with A. Severe Plasma Volume Expansion (PV ≥ Median of +26% Above Normal Volume) B. Mild-Moderate Plasma Volume Expansion (PV < Median of +26% Above Normal Volume)

Physiological and Molecular Responses to Altered Sodium Intake in Rat Pregnancy.

BackgroundIn pregnancy, a high plasma volume maintains uteroplacental perfusion and prevents placental ischemia, a condition linked to elevated maternal blood pressure (BP). Reducing BP by increasing Na+ intake via plasma volume expansion appears contra‐intuitive. We hypothesize that an appropriate Na+ intake in pregnancy reduces maternal BP and adapts the renin‐angiotensin system in a pregnancy‐specific manner.Methods and Results BP was measured by implanted telemetry in Sprague‐Dawley rats before and throughout pregnancy. Pregnant and nonpregnant animals received either a normal‐salt (0.4%; NS), high‐salt (8%; HS), or low‐salt (0.01%; LS) diet, or HS (days 1–14) followed by LS (days 14–20) diet (HS/LS). Before delivery (day 20), animals were euthanized and organs collected. Food, water, and Na+ intake were monitored in metabolic cages, and urinary creatinine and Na+ were analyzed. Na+ intake and retention increased in pregnancy (NS, LS), leading to a positive Na+ balance (NS, LS). BP was stable during LS, but reduced in HS conditions in pregnancy. The renin‐angiotensin system was adapted as expected. Activating cleavage of α‐ and γ‐subunits of the renal epithelial Na+ channel and expression of‐full length medullary β‐subunits, accentuated further in all LS conditions, were upregulated in pregnancy.ConclusionsPregnancy led to Na+ retention adapted to dietary changes. HS exposure paradoxically reduced BP. Na+ uptake while only modestly linked to the renin‐angiotensin system is enhanced in the presence of posttranslational renal epithelial Na+ channel modifications. This suggests (1) storage of Na+ in pregnancy upon HS exposure, bridging periods of LS availability; and (2) that potentially non–renin‐angiotensin–related mechanisms participate in ENaC activation and consecutive Na+ retention.

Quantitative analysis of dextran in rat plasma using Q-Orbitrap mass spectrometry based on all ion fragmentation strategy

Dextran is a biocompatible glucose-based polymer that is widely used clinically as a plasma volume expander, anti-thrombotic agent, macromolecular carrier, peripheral blood flow enhancer, and artificial tears promoter. Because dextran has polydisperse molecular weights and tends to produce innumerable multi-charged precursor ions in the ion source, it is difficult to analysis this polymer using conventional liquid chromatography mass spectrometry. In this assay, all ion fragmentation strategy is used to solve this problem by allowing all dextran precursor ions generated in the ion source to enter the collision cell. Then serial dextran-specific fragments can be effectively generated from all precursor ions by higher energy collision dissociation and scanned by Orbitrap detector. These high resolution fragment ions provide high specificity and sensitivity for the quantitation of dextran in rat plasma. Here, we report a new quantitative method using size exclusion chromatography combined with Q Exactive mass spectrometry based on an all ion fragmentation strategy. Assay validation showed that this method is linear over the concentration range from 3 to 300 μg/mL. Our approach has been successfully applied to a pharmacokinetic study of dextran in rat and will promote the development of studies with other polysaccharides.