Plasma Volume Expansion Research Articles

Mechanisms Underlying Exacerbation of Osmotic Nephrosis Caused by Pre-existing Kidney Injury.

Osmotic nephrosis, a disease caused by intravenous infusion of various fluids such as hypertonic sucrose and isotonic polysaccharide-based plasma volume expanders, exhibits specific histopathological features, including vacuolated and swollen proximal tubules, ie, "clear tubules". Pre-existing kidney injury exacerbates this condition, resulting in major clinical problems. However, the underlying mechanisms are unclear. Animal models often yield results that are directly translatable to humans. Therefore, in this study, we performed detailed histopathological analyses of the formation of clear tubules in rats treated with gentamicin or ischemia/reperfusion (IR) operation followed by dextran administration. The results showed that clear tubules may originate from regenerative tubules. Additionally, we classified regenerative tubules into 3 categories based on their development, with a particular focus on the middle and late stages. Comprehensive microarray and real-time polymerase chain reaction analyses of mRNA extracted from regenerative tubules at each stage using laser microdissection revealed that regenerative tubules in the middle stage showed an imbalance between dextran absorption and metabolism, resulting in accumulation of dextran, particularly in the cytoplasm of the tubules. Overall, our findings demonstrated that clear tubules originated from regenerated tubules and that tubules at the middle stage became clear tubules because of an imbalance during their development. This could explain why osmotic nephrosis is exacerbated in the presence of kidney lesions.

Heart failure with preserved ejection fraction: from mechanisms to therapies.

This review aims to provide a translational perspective on recent developments in heart failure with preserved ejection fraction (HFpEF), linking mechanistic insights to potential therapies. A key concept in this review is that HFpEF is a haemodynamic condition wherein the heart fails to keep up with the circulatory demands of the body, or does so at the expense of raised left ventricular filling pressures. We, therefore, propose that the 'final common pathway' for development of congestion, i.e. basic haemodynamic mechanisms of increased left ventricular end-diastolic pressure, left atrial hypertension, pulmonary venous congestion, and plasma volume expansion, represents important initial targets for therapy in HFpEF. Accordingly, we group this review into six mechanisms translating into potential therapies for HFpEF: beginning with three haemodynamic mechanisms (left atrial hypertension, pulmonary hypertension, and plasma volume expansion), and working backward to three potential molecular mechanisms [systemic microvascular inflammation, cardiometabolic functional abnormalities, and cellular (titin)/extracellular (fibrosis) structural abnormalities].

The independent effects of hypovolaemia and pulmonary vasoconstriction on ventricular function and exercise capacity during acclimatisation to 3800m.

We sought to determine the isolated and combined influence of hypovolaemia and hypoxic pulmonary vasoconstriction on the decrease in left ventricular (LV) function and maximal exercise capacity observed under hypobaric hypoxia. We performed echocardiography and maximal exercise tests at sea level (344m), and following 5-10days at the Barcroft Laboratory (3800m; White Mountain, California) with and without (i) plasma volume expansion to sea level values and (ii) administration of the pulmonary vasodilatator sildenafil in a double-blinded and placebo-controlled trial. The high altitude-induced reduction in LV filling and ejection was abolished by plasma volume expansion but to a lesser extent by sildenafil administration; however, neither intervention had a positive effect on maximal exercise capacity. Both hypovolaemia and hypoxic pulmonary vasoconstriction play a role in the reduction of LV filling at 3800m, but the increase in LV filling does not influence exercise capacity at this moderate altitude. We aimed to determine the isolated and combined contribution of hypovolaemia and hypoxic pulmonary vasoconstriction in limiting left ventricular (LV) function and exercise capacity under chronic hypoxaemia at high altitude. In a double-blinded, randomised and placebo-controlled design, 12 healthy participants underwent echocardiography at rest and during submaximal exercise before completing a maximal test to exhaustion at sea level (SL; 344m) and after 5-10days at 3800m. Plasma volume was normalised to SL values, and hypoxic pulmonary vasoconstriction was reversed by administration of sildenafil (50mg) to create four unique experimental conditions that were compared with SL values: high altitude (HA), Plasma Volume Expansion (HA-PVX), Sildenafil (HA-SIL) and Plasma Volume Expansion with Sildenafil (HA-PVX-SIL). High altitude exposure reduced plasma volume by 11% (P<0.01) and increased pulmonary artery systolic pressure (19.6±4.3 vs. 26.0±5.4, P<0.001); these differences were abolished by PVX and SIL respectively. LV end-diastolic volume (EDV) and stroke volume (SV) were decreased upon ascent to high altitude, but were comparable to sea level in the HA-PVX trial. LV EDV and SV were also elevated in the HA-SIL and HA-PVX-SIL trials compared to HA, but to a lesser extent. Neither PVX nor SIL had a significant effect on the LV EDV and SV response to exercise, or the maximal oxygen consumption or peak power output. In summary, at 3800m both hypovolaemia and hypoxic pulmonary vasoconstriction contribute to the decrease in LV filling, but restoring LV filling does not confer an improvement in maximal exercise performance.

Recruitment of extravascular fluid by hyperoncotic albumin.

Although hyperoncotic albumin may be used to recruit oedema, its effectiveness remains unclear. Therefore, this issue was studied during infusion experiments in healthy volunteers. Fifteen healthy volunteers (mean age 31years) received an infusion of 3mL/kg of 20% albumin over 30minutes. Their urinary excretion was recorded, and venous blood samples were taken to measure blood haemoglobin (Hb), haematocrit, colloid osmotic pressure as well as plasma albumin and sodium concentrations on 15 occasions over a period of 300minutes. Plasma volume expansion was taken as the inverse of the fluid-induced dilution of venous plasma, as given by the blood Hb concentration. Mass balance calculations were used to estimate the mobilisation of fluid from the tissues. Maximum plasma volume expansion was reached 20minutes after completing an infusion of 20% albumin. Urinary excretion was effectively increased, and the mobilised fluid from the tissues at 300minutes amounted to 3.4±1.2mL for each infused mL of 20% albumin, of which 19% was of intracellular origin. The urinary excretion correlated strongly with the amount of recruited fluid (R2 =0.87) and inversely with the plasma volume expansion (R2 =0.53). The infusion of 20% albumin significantly increases the plasma volume by recruiting interstitial fluid. After completing the infusion, there is a delay of 20minutes until maximum plasma dilution is reached, and the duration of the plasma volume expansion lasts far beyond 5hours.

Pacing of an Untrained 17-Year-Old Teenager in a Marathon Attempt.

Although there has been increased scientific interest for physiological responses to endurance running and pacing, limited information exists for adolescents participating in endurance events. We are reporting the case of an untrained 17-year-old female teenager (body mass 50.6 kg, height 167 cm and body mass index 18.1 kg/m2) who intended to run a marathon within 6 hours without preparation. The young woman missed her goal by just 2 km. When the average running speed per hour was analysed, there was a major effect of race hour on running speed (p = 0.013, η2 = 0.320), where the running speed in the fifth hour (6.3 ± 0.2 km/h) was lower than in the second hour (6.9 ± 0.1 km/h). Despite a progressive decrease in running speed, she was still able to put on a final spurt, indicated by a 4th degree non-linear regression (R2=0.55). Creatine-kinase reached the initial value again after 5 days and the fall of hemoglobin and hematocrit indicated expansion of plasma volume. Running a marathon as a teenager did not impair physical health, especially when a self-selected pace was adopted. Laboratory parameters during running showed similar changes as have been reported for teenagers and adults after running a marathon. Increased values returned to base line within a few days. In summary, a female teenager at the age of 17 years without specific running preparation is able to achieve nearly a marathon distance during 6 hours of continuous running without harmful effects on health.

Effects of Increased Preload on Cardiac Function in Younger vs Older Women

PURPOSE: Limitations in cardiac preload and/or compliance could underlie diminished stroke volume and ventricular remodeling adaptations to endurance exercise in older women. The present study tested the hypothesis that attenuated cardiac function in older women persists during acute increases in preload, both at rest and during exercise. METHODS: Nine younger (Y, 21-28 y) and ten older (O, 61-73 y) healthy, non-endurance trained women were studied 1) at rest in the supine and seated positions, and 2) during graded upright cycle ergometer exercise (20, 40, 60 and 80% of VO2peak), both before and after acute plasma volume (PV) expansion (via IV infusion of 5% albumin; 10ml/kg). Cardiac responses to postural change, exercise, and PV expansion were measured using echocardiography (rest and low intensity exercise) and open circuit C2H2 (exercise). RESULTS: Under resting normovolemic conditions, stroke volume (SV) was augmented in the supine (vs. upright) posture in both Y (61±9 vs. 52±8 ml/beat, P<0.05) and O (55±10 vs. 49±7 ml/beat, P<0.05) women. Hypervolemia augmented supine SV further in Y (68±4 ml/beat, P<0.05 vs. normovolemia), but not in O (55±10 ml/ beat, P>0.05 vs. normovolemia) women. These resting postural and hypervolemic effects were mediated by changes in end diastolic volume, and not secondary to age group differences in the extent of PV expansion (averaged +16% and +13% in Y and O, respectively) or estimated filling pressures (E/E’). E/A ratio during peak resting preload conditions (i.e., supine hypervolemia), moreover, was positively associated with VO2peak in Y, but not in O women. During upright exercise, hypervolemia increased SV an average of 15 ml/beat across all 4 work intensities in Y women (p<0.05 vs. normovolemia). This was in contrast to O women, who exhibited very small increases in SV during hypervolemic exercise (i.e., <5 ml/beat). CONCLUSIONS: Healthy older women appear to have a reduced ability (relative to younger women) to utilize acute increases in preload to raise left ventricular stroke volume, including during large muscle exercise. These findings likely reflect the combined effects of exceptional lusitropic function in younger women, and a less compliant ventricle in the aged female heart.

Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity.

Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits.

Exercise in a warm condition enhances plasma volume expansion compared to a cool condition with an increased skin but not core temperature

Plasma volume (PV) expansion is a fundamental physiological adaptation to exercise‐heat acclimation. We investigated the effects of an increased body core temperature and skin temperatures on PV expansion after intense exercise.METHODSEight healthy young men underwent two identical trials which differs only ambient temperature (Ta) during exercise. On day 1, baseline blood sample was taken in a thermoneutral condition, then they performed a 72‐min intense‐intermittent exercise (8 sets of 4 min at 80% VO2max – 5 min at 20% VO2max) under cool (Ta of 20°C) and warm (Ta of 30°C) conditions. On day 2, after 23 hours after exercise, blood sample was taken again in the thermoneutral condition. We measured hematocrit, hemoglobin concentration, and plasma albumin and protein concentrations, and from these data, percent change in PV (Δ%PV) and in plasma albumin and total protein content (Δ%Albcont and Δ%TPcont, respectively) from baseline were determined. Esophageal temperature (Tes) and mean skin temperature (Tsk) were measured during exercise.RESULTSDuring exercise, Tsk were higher (p &lt; 0.05) in warm than cool condition while Tes was comparable between trials. Δ%PV was higher in warm condition than cool condition (6.8 ± 1.3 % and 3.3 ± 1.3 %, means ± SE, p &lt; 0.05), Δ%Albcont and Δ%TPcont were also higher in warm condition than cool condition (both, p &lt; 0.05).CONCLUSIONSExercise in a warm condition enhances plasma volume expansion with plasma protein content after intense exercise compared with a cool condition, which is associated with an increased skin temperatures but not core temperature. Thus, increase in skin temperatures would be a possible target to enhance physiological adaptation to exercise‐heat acclimation.Support or Funding InformationThis work was supported by a Grant‐in‐Aid for Scientific Research (B) and a Grant‐in‐Aid for Challenging Exploratory Research (K. Okazaki) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of a nitric oxide donor on maternal hemodynamics in fetal growth restriction

To evaluate the effect on maternal cardiovascular parameters of treatment with a nitric oxide (NO) donor and plasma volume expansion in pregnancies complicated by fetal growth restriction (FGR). Twenty-six pregnant women with a diagnosis of FGR were treated with transdermal patches of a NO donor and plasma volume expansion by co-administration of oral fluids. We compared the treated group to a historical control group of untreated FGR patients. Hemodynamic indices were obtained using the UltraSonic Cardiac Output Monitor system. At diagnosis, the two groups were similar in terms of maternal and hemodynamic characteristics. In the treated group, we found a significant increase in maternal cardiac output and stroke volume and a decrease in systemic vascular resistance after 2 weeks of therapy. No significant differences were found 2 weeks after diagnosis in the untreated group. The treated group delivered infants with higher birth-weight centile than did the untreated control group. The combined therapeutic approach of NO donor administration and plasma volume expansion in FGR apparently improves significantly maternal hemodynamic indices. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Hypertonic saline infusion affects glycemic responses following glucose load in healthy men

Low water intake and plasma hypertonicity have been independently associated with hyperglycemia and incidence of diabetes mellitus in epidemiological studies. Recent data also suggest that reducing water intake deteriorates glucose regulation in patients with type 2 diabetes. To date, it is unclear whether plasma hypertonicity would also impact glycemic control in subjects with normal glycemic and insulinemic function.OBJECTIVETo assess the effect of hypertonic saline infusion on glycemic responses to an oral glucose tolerance test (OGTT) in healthy adult men.METHODS30 healthy, non‐smoking adult men (36.6±7.0 y, 83.9±12.8 kg, body mass index 27.0±3.4 kg·m−2, HbA1c 5.2±0.3%, HOMA‐IR 1.59±0.97) were recruited for this study. Each subject underwent two experimental trials, consisting of a 2‐h intravenous infusion of saline (ISO: 0.9% NaCl and HYPER: 3.0% NaCl) at an infusion rate of 0.1 ml·kg·min−1, followed by a 4‐h oral OGTT. Blood samples were taken at 30 min intervals throughout the infusion period and during the OGTT. Plasma osmolality (POsm), glucose (Glu), angiotensin II (AngII), renin, and aldosterone (Ald) were measured and plasma volume (PV) was calculated using hematocrit and hemoglobin based on the Dill &amp; Costill equation.RESULTSPOsm at baseline was similar between conditions (287±3 and 286±3 mmol·kg−1 in HYPER and ISO, respectively). Following the 2‐h infusion, POsm was significantly higher in the HYPER condition than the ISO condition (305‐±3 vs. 288±3 mmol·kg−1; P &lt; 0.0001), with greater PV expansion (20.1±6.9 vs. 10.9±3.2%, P &lt; 0.0001). In the HYPER condition, POsm remained above baseline throughout the OGTT (296±3 mmol·kg−1 at OGTT4‐h; P &lt; 0.0001). During the OGTT, Glu in the HYPER trial was higher than in the ISO trial at 60 min (HYPER: 157±24; ISO: 145±29 mg·dL−1; P &lt; 0.018) and 90 min (HYPER: 139±33; ISO 128±29 mg·dL−1; P &lt; 0.038). The renin‐angiotensin‐aldosterone system was suppressed as indicated by decreased plasma values of AngII, renin, and Ald, probably due to PV expansion in both trials.CONCLUSIONPlasma hypertonicity induced by hypertonic saline infusion unfavorably affected glycemic response to an OGTT in healthy adult men.Support or Funding InformationThis research was supported by Danone ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Copeptin Responses to Isotonic and Hypertonic Saline Infusion in Healthy Adults

Copeptin, a c‐terminal segment of arginine vasopressin (AVP) prohormone, has equimolar secretion to AVP in response to osmotic, stress‐related, and hemodynamic stimulation. For this reason, and because of the difficulties in measuring AVP directly linked to its short half‐life, copeptin has been used as a stable and sensitive surrogate marker for AVP for various clinical indications. However, the plasma copeptin response to osmotic stimulation remains poorly documented.PURPOSEExamine the plasma copeptin response to plasma hyperosmolality induced by hypertonic saline infusion.METHODSSixty healthy adults (50% male, age: 30±1 y, weight: 78.2±15.2 kg, body mass index: 26.9±4.0 kg·m−2) were infused intravenously with 3% (HYPER) or 0.9% (ISO) NaCl for 2 h (0.1 ml·kg−1·min−1) in a counterbalanced, cross‐over design. Blood samples were collected every 30 minutes. Plasma osmolality (POsm), copeptin (PCop; BRAHAMS copeptin proAVP, Thermo Fisher Scientific, Germany), and sodium (PNa) were measured, and changes in plasma volume (PV) were calculated from hematocrit and hemoglobin using the Dill &amp; Costill equation.RESULTSFollowing the HYPER trial, PNa increased from 136±2 mmol ·L−1 to 146.5±3 mmol ·l−1 (P &lt; 0.001), with PV expansion of 18.7±7.3% (P &lt; 0.001). Both POsm and PCop increased significantly (0 min: 286±3 mmol·kg−1 and 4.5±3.7 pmol·L−1; 120 min: 305±4 mmol·kg−1 and 20.4±12.8 pmol·L−1, respectively, P &lt; 0.001). Mean (95% CI) PCop increased with increasing POsm: 3.2 (2.5–3.8) pmol·L−1 for POsm ≤ 284.9 mmol·kg−1; 5.4 (3.8–7.0) pmol·L−1 for POsm 285–289.9; 6.2 (4.3–8.0) pmol·L−1 for POsm 290–294.9; 8.5 (7.1–9.9) pmol·L−1 for POsm 295–299.9; 12.3 (10.2–14.4) pmol·L−1 for POsm 300–304.9; and 19.2 (16.3–22.2) pmol·L−1 for POsm ≥ 305 mmol·kg−1. In contrast, during the ISO trial PNa remained unchanged during the 2‐h infusion (135.9±1.9 vs. 137.6±1.6 mmol·L−1), while PV expanded by 10.5±4.4% (P &lt; 0.001 compared to baseline; P &lt; 0.001 compared to HYPER). Neither POsm (0 min: 285±4,120 min: 287±3 mmol·kg−1) nor PCop (0 min: 4.1±1.8, 120 min: 3.8±3.0 pmol·L−1) were affected during the ISO trial.CONCLUSIONPlasma copeptin was stimulated by increased plasma osmolality during a hypertonic infusion.Support or Funding InformationThis research was supported by Danone ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Derangements in adrenergic-adipokine signalling establish a neurohormonal basis for obesity-related heart failure with a preserved ejection fraction.

Among patients with heart failure and a preserved ejection (HFpEF), obesity is associated with a distinct phenotype that is characterized by adiposity-driven plasma volume expansion and cardiac overfilling, which is coupled with an impairment of ventricular distensibility. These pathophysiological abnormalities may be related to the increased actions of specific adipocyte-derived signalling molecules (aldosterone, neprilysin and leptin) that work in concert with increased renal sympathetic nerve traffic and activated beta2 -adrenergic receptors to promote sodium retention, microvascular rarefaction, cardiac fibrosis and systemic inflammation. This interplay leads to striking activation of the mineralocorticoid receptor, possibly explaining why obese patients with heart failure are most likely to benefit from spironolactone and eplerenone in large-scale clinical trials. Additionally, adipocytes express and release neprilysin, which (by degrading endogenous natriuretic peptides) can further promote plasma volume expansion and cardiac fibrosis. Heightened neprilysin activity may explain the low circulating levels of natriuretic peptides in obesity, the accelerated breakdown of natriuretic peptides in HFpEF, and the cardiac decompression following neprilysin inhibition in HFpEF patients who are obese. Furthermore, as adipose tissue accumulates and becomes dysfunctional, its secretion of leptin promotes renal sodium retention, microvascular changes and fibrotic processes in the heart, and systemic inflammation; these effects may be mediated or potentiated by the activation of beta2 -adrenergic receptors. These adrenergic-adipokine interactions provide a mechanistic framework for novel therapeutic strategies to alleviate the pathophysiological abnormalities of obesity-related HFpEF. Ongoing trials are well-positioned to test this hypothesis.

CALCULATED PLASMA VOLUME STATUS PREDICTS EARLY AND LATE OUTCOMES AFTER CORONARY ARTERY BYPASS GRAFTING

Plasma volume (PV) expansion underlies systemic congestion in coronary artery bypass graft (CABG) patients (pts) & can be substantial despite clinical euvolemia. We tested the utility of calculated PV status (PVS) in this cohort. Calculated PVS, a validated formula that enumerates % change from

Pregnancy Alters Renal and Blood Burden of Mercury in Females.

Methylmercury (CH3Hg+), a common environmental toxicant, has serious detrimental effects in numerous organ systems. We hypothesize that a significant physiological change, like pregnancy, can alter the disposition and accumulation of mercury. To test this hypothesis, pregnant and non-pregnant female Wistar rats were exposed orally to CH3Hg+. The amount of mercury in blood and total renal mass was significantly lower in pregnant rats than in non-pregnant rats. This finding may be due to expansion of plasma volume in pregnant rats and dilution of mercury, leading to lower levels of mercury in maternal blood and kidneys.

Do sodium-glucose co-transporter-2 inhibitors prevent heart failure with a preserved ejection fraction by counterbalancing the effects of leptin? A novel hypothesis.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis. Interestingly, leptin-mediated neurohormonal activation appears to enhance the expression of SGLT2 in the renal tubules, and SGLT2 inhibitors exert natriuretic actions at multiple renal tubular sites in a manner that can oppose the sodium retention produced by leptin. In addition, SGLT2 inhibitors reduce the accumulation and inflammation of perivisceral adipose tissue, thus minimizing the secretion of leptin and its paracrine actions on the heart and kidneys to promote fibrosis. Such fibrosis probably contributes to the impairment of cardiac distensibility and glomerular function that characterizes obesity-related HFpEF. Ongoing clinical trials with SGLT2 inhibitors in heart failure are positioned to confirm or refute the hypothesis that these drugs may favourably influence the course of obesity-related HFpEF by their ability to attenuate the secretion and actions of leptin.

Polycythemia Vera.

Polycythemia vera (PV) is the most common myeloproliferative neoplasm (MPN), the ultimate phenotype of the JAK2 V1617F mutation, the MPN with the highest incidence of thromboembolic complications, which usually occur early in the course of the disease, and the only MPN in which erythrocytosis occurs. The classical presentation of PV is characterized by erythrocytosis, leukocytosis, and thrombocytosis, often with splenomegaly and occasionally with myelofibrosis, but it can also present as isolated erythrocytosis with or without splenomegaly, isolated thrombocytosis or isolated leukocytosis, or any combination of these. When PV is present, the peripheral blood hematocrit (or hemoglobin) determination will not accurately represent the actual volume of red cells in the body, because in PV, in contrast to other disorders causing erythrocytosis, when the red cell mass increases, the plasma volume usually increases. In fact, unless the hematocrit is greater than 59%, true erythrocytosis cannot be distinguished from pseudoerythrocytosis due to plasma volume contraction. Usually, the presence of splenomegaly or leukocytosis or thrombocytosis establishes the diagnosis. However, when a patient presents with isolated thrombocytosis and a positive JAK2 V617F assay, particularly a young woman, the possibility of PV must always be considered because of plasma volume expansion. The WHO PV diagnostic guidelines are not helpful in this situation, since the hematocrit is invariably normal and a bone marrow examination will not distinguish ET from PV. Only a direct measurement of both the red cell mass and plasma volume can establish the correct diagnosis. In managing a PV patient, it is important to remember that PV is an indolent disorder in which life span is usually measured in decades, even when myelofibrosis is present, that chemotherapy is futile in eradicating the disease but does increase the incidence of acute leukemia and that hydroxyurea is not safe in this regard nor is it antithrombotic. Phlebotomy to a sex-specific normal hematocrit is the cornerstone of therapy and there now exist safe remedies for controlling leukocytosis, thrombocytosis, and extramedullary hematopoiesis and symptoms due to inflammatory cytokines when this is necessary.

Limited Effects of Short-Term Heat Acclimation during a Rugby League Training Week

We investigated the effects of five consecutive days of short-term heat acclimation (STHA), with a 48-h recovery, on simulated rugby league performance, peak oxygen uptake (V O2peak), physiological and perceptual responses in a temperate environment. Twelve male rugby league players took part in a matched-pairs design, cycling 60-min/day, for five days at 40% V O2peak, in a control (19 ± 1 °C; 50 ± 3 % RH; n = 6) or STHA group (33 ± 0.5 °C; 70 ± 4 % RH; n = 6). Subjects completed a V O2peak test and rugby simulation, followed by a time-to-exhaustion, pre- and post-intervention, with physiological and perceptual responses measured during the interventions. Despite no effect on simulated performance (P > 0.05), there were increases in time-to-exhaustion among both groups (P = 0.016), without group effects (P = 0.802). The STHA group adapted across the intervention, with lower tympanic temperature, perceptual responses and heart rate over time (P < 0.05), which were typically higher than the control group (P < 0.05). Plasma volume did not increase over time or change between groups (P = 0.290) and V O2peak reduced pre-to-post (P < 0.001). There was a relationship between body mass losses and plasma volume expansion (r = -0.79, P = 0.022). STHA improved tolerance to the heat but not performance in simulated matches or exhaustive tests in temperate conditions, compared to thermoneutral exercise. The limited effects of STHA might relate to the brief post-intervention recovery period or the lack of fluid ingestion control during acclimation.

Prevention of Pre-Eclampsia and Eclampsia. A Systematic Review

Every pregnant woman needs continuous, timely and supportive care throughout during pregnancy for safe motherhood. The objective of this study was to analyze and evaluate the available medications and techniques for the prevention and treatment of pre-eclampsia and eclampsia. The standard methodology of systematic review without meta-analysis was followed and only RCTs and systematic reviews were included in the review. Three electronic data sources (PubMed/Medline, CINAHL, and Cochrane) were searched for studies, published between 1986 and 2016 on the prevention and control of pre-eclampsia and eclampsia. 47 studies were finally included in the review, of which 18 were systematic reviews and 29 were RCTs. Technologies and techniques used in the included studies for the prevention and control of pre-eclampsia and eclampsia are Magnesium Sulphate, Aspirin, Antioxidant (Vitamin C, E and Lycopene), Calcium supplementation, Chinese Herbal Medicine, physical activities, Nitric Oxide, Marine Food Oils, Low Salt Diet, Garlic, Plasma Volume Expansion, Low-dose Dopamine, Progesterone, Smoking, and Diuretics. Magnesium sulfate appears to be the most effective treatment which reduces the risk of eclampsia by more than 50%. However, its best dose and route are still controversial and need further research. The knowledge and experience of nurses in properly using the protocols and evidence-based interventions are necessary for the wellbeing of pregnant women.

Interval Walking Training and Nutritional Intake to Increase Plasma Volume in Elderly.

Aerobic training-induced plasma volume (PV) expansion improves thermoregulation, and carbohydrate (CHO) + whey protein supplementation enhanced the effects in older people; however, these were suggested by studies on gym-based cycling training but not on home-based interval walking training (IWT). Moreover, long-term walking training effects on PV remain unknown. Seventeen male and 10 female subjects (~69 yr), having performed IWT for ≥24 months before the study, were used. After pre-intervention measurement (PRE) of PV, plasma albumin content (Albcont), fasting glucose concentration ([Glc]f), and HbA1c, the subjects were randomly divided into two groups: CHO and Pro-CHO, either consuming CHO (22.5 g) alone or CHO (15 g) + whey protein (10 g), respectively, during additional 5-month IWT from May to November, 2009. After the additional IWT, we measured the same variables again (postintervention measurement). The baseline PV and Albcont were significantly correlated with the number of IWT days for the 12 months preceding PRE (r = 0.716, P < 0.001 and r = 0.671, P < 0.001, respectively). In postintervention, PV and Albcont marginally decreased in CHO from the baselines (P = 0.081 and P = 0.130, respectively) with increased HbA1c (P < 0.001) after correction for the baseline [Glc]f by ANCOVA, but these values remained unchanged in Pro-CHO (both, P > 0.74), with significant differences in the changes between groups (P = 0.020, P = 0.041, and P = 0.018 respectively). PV was proportional to the number of IWT days for 12 months and a CHO + whey protein supplementation during the 5-month IWT prevented PV reduction for the period of no supplementation, which might be partially linked with blood glucose control mechanisms.

The influence of fluid management on outcomes in preeclampsia: a systematic review and meta-analysis

BackgroundThe optimal fluid management strategy to ensure best outcomes in preeclamptic patients remains a controversial issue, with little evidence to support any one approach. ObjectiveThe aim of this systematic review was to investigate the effect of various fluid management strategies on clinical outcomes, haemodynamic indices and biochemical markers in preeclamptic women and their babies. Primary outcome measures were the occurrence of pulmonary oedema and/or the development of renal impairment. MethodsA systematic review of randomised fluid management strategies was conducted. Five electronic databases were searched using the expanded search terms: ‘intravenous fluid’, ‘plasma substitutes’, ‘intravenous fluid management’, ‘intravenous fluid therapy’, plasma volume expansion’, ‘fluid restriction’, ‘oncotic therapy’, ‘crystalloids’, ‘colloids’, ‘preeclampsia’, ‘toxemia of pregnancy’, ‘pregnancy-induced hypertension’, ‘eclampsia’ and ‘gestational proteinuric hypertension’. ResultsSix randomised controlled trials (RCTs), from nine publications, were included in the final analysis. There were no differences between groups with respect to the incidence of pulmonary oedema, perinatal mortality, preterm delivery and caesarean section. Colloid volume expansion was associated with a significantly lower systolic and diastolic blood pressure, but had no effect on heart rate or cardiac index. Data on systemic vascular resistance (SVR), serum atrial natriuretic peptide (ANP) and urine volume could not be aggregated. ConclusionData on the ideal fluid strategy in women with preeclampsia is limited, and insufficient to make any strong recommendations. Further randomised controlled studies are needed to provide more evidence for which fluid management strategies are best suited to this heterogeneous patient group.