Reduction In Plasma Volume Research Articles

Long-term spaceflight and the cardiovascular system.

While early investigations into the physiological effects of spaceflight suggest the body's ability to reversibly adapt, the corresponding effects of long-term spaceflight (>6 months) are much less conclusive. Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system, including a massive cephalad fluid translocation and altered arterial pressure, which attenuate blood pressure regulatory mechanisms and increase cardiac output. Also, central venous pressure decreases as a result of the loss of venous compression. The stimulation of baroreceptors by the cephalad shift results in an approximately 10%–15% reduction in plasma volume, with fluid translocating from the vascular lumen to the interstitium. Despite possible increases in cardiac workload, myocyte atrophy and notable, yet unexplained, alterations in hematocrit have been observed. Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action. While data are scarce regarding their causative agents, arrhythmias have been frequently reported, albeit sublethal, during both Russian and American expeditions, with QT interval prolongation observed in long, but not short duration, spaceflight. Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration, aortic stiffness, carotid intima thickening via collagen-mediated action, accelerated atherosclerosis, and induction of a pro-inflammatory state. Upon return, long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses, which can prove hazardous should any rapid mobilization or evacuation be required, and indicates that these cardiac risks should be especially monitored for future missions.

Short-term very low caloric intake causes endothelial dysfunction and increased susceptibility to cardiac arrhythmias and pathology in male rats.

New Findings What is the central question of this study? What are the effects of a 2 week period of severe food restriction on vascular reactivity of resistance arteries and on cardiac structure and function? What is the main finding and its importance? This study showed, for the first time, that a 2 week period of severe food restriction in adult male Fischer rats caused endothelial dysfunction in mesenteric arteries and increased the susceptibility to ischaemia–reperfusion‐induced arrhythmias and cardiac pathology. Our findings might have ramifications for cardiovascular risk in people who experience periods of inadequate caloric intake. Severe food restriction (sFR) is a common dieting strategy for rapid weight loss. Male Fischer rats were maintained on a control (CT) or sFR (40% of CT food intake) diet for 14 days to mimic low‐calorie crash diets. The sFR diet reduced body weight by 16%. Haematocrits were elevated by 10% in the sFR rats, which was consistent with the reduced plasma volume. Mesenteric arteries from sFR rats had increased sensitivity to vasoconstrictors, including angiotensin II [maximum (%): CT, 1.30 ± 0.46 versus sFR, 11.5 ± 1.6; P < 0.0001; n = 7] and phenylephrine [maximum (%): CT, 78.5 ± 2.8 versus sFR, 94.5 ± 1.7; P < 0.001; n = 7] and reduced sensitivity to the vasodilator acetylcholine [EC50 (nm): CT, 49.2 ± 5.2 versus sFR, 71.6 ± 6.8; P < 0.05; n = 7]. Isolated hearts from sFR rats had a 1.7‐fold increase in the rate of cardiac arrhythmias in response to ischaemia–reperfusion and more cardiac pathology, including myofibrillar disarray with contractions and cardiomyocyte lysis, than hearts from CT rats. The sFR dietary regimen is similar to very low‐calorie commercial and self‐help weight‐loss programmes, which provide ∼800–1000 kcal day−1. Therefore, these findings in rats warrant the study of cardiovascular function in individuals who engage in extreme dieting or are subjected to bouts of very low caloric intake for other reasons, such as socioeconomic factors and natural disasters.

1133-P: Association of Higher Baseline BNP Levels with a Greater Reduction in Plasma Volume and Increase in Beta-Hydroxybutyrate via the SGLT2 Inhibitor Tofogliflozin in Type 2 Diabetes

Reduced plasma volume (PV) to decrease ventricular filling pressure and increased beta-hydroxybutyrate (BHB) as a substitute for the energy source by SGLT2 inhibitors (SGLT2is) might contribute to preserving the heart in type 2 diabetes mellitus (T2DM). However, the impact of SGLT2is on PV and BHB is little known according to cardiac workload. We investigated the effect of long-term treatment with the SGLT2i, tofogliflozin, on PV and BHB according to baseline brain natriuretic peptide (BNP) levels in T2DM. Analyzed were 774 T2DM patients who received tofogliflozin for 52 weeks as mono- and add-on-therapy in two phase-3 studies. Percent change in estimated PV (%ΔePV) was calculated by the Strauss formula: {100*(pre Hb/post Hb)*[(100 - post Ht)/(100 - pre Ht)] - 100}. We divided patients into two groups (Quartiles 1-3[Q1-3] and Quartile 4[Q4]) according to baseline BNP. Differences in characteristics were analyzed using unpaired t-test, wilcoxon rank sum test or Fisher’s exact test. Differences in changes between groups were analyzed using an analysis of covariance model. Multivariate analysis evaluated the association of baseline BNP with changed variables. Baseline characteristics were: male (71 vs. 52% *, * p&amp;lt;0.05, Q1-3 vs. Q4), age (mean: 57 vs. 64 y *), HbA1c (8.1 vs. 8.0%), BMI (26 vs. 25 kg/m2 *), BNP (median: 9 vs. 27 pg/mL *) and BHB (45 vs. 54 µmol/L). Reduction in Ln-transformed BNP (ln-BNP) was greater in Q4 (least square mean: -0.5 ln[pg/mL]) than in Q1-3 (-0.1) as was %ΔePV (Q4 [-6 %] vs. Q1-3 [-4]). Increase in Ln-transformed BHB (ln-BHB) was larger n Q4 (+0.7 ln[µmol/L]) than in Q1-3 (+0.5). Changes in HbA1c, body weight and blood pressure were similar. Q4 was independently correlated with the greater reduction in %ΔePV and increase in ln-BHB. Results suggested that reduced PV and increased BHB might be greater in T2DM patients with higher baseline BNP levels after long-term tofogliflozin therapy. Disclosure A. Yoshida: Employee; Self; Kowa Company, Ltd. Y. Matsubayashi: None. T. Nojima: Employee; Self; Kowa Company, Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd. M. Oe: Employee; Self; Kowa Company, Ltd. K. Fujihara: None. S. Tanaka: None. K. Kaku: Advisory Panel; Self; Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc. Consultant; Self; Sanwa Kagaku Kenkyusho. Research Support; Self; Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

1125-P: Association of Plasma Volume with Body Weight and BNP after Long-Term Administration and Subsequent Withdrawal of the SGLT2 Inhibitor Tofogliflozin

SGLT2 inhibitors (SGLT2is) promote diuresis and reduce plasma volume (PV). However, the impact of long-term administration and subsequent withdrawal of SGLT2is on PV is little known. This study investigated the effect of long-term administration and then withdrawal of the SGLT2i, tofogliflozin (TOFO), on PV and explored correlations with variables in type 2 diabetes mellitus (T2DM). Analyzed were 166 T2DM patients who received TOFO for 52 weeks as initial monotherapy and underwent 2 weeks of withdrawal (week 54) in a phase-3 study. Percent change in estimated PV (%ΔePV) was calculated by the Strauss formula: {100*(pre Hb/post Hb)*[(100 - pre Ht)/(100 - post Ht)] - 100}. Baseline characteristics were: male (66%), age (mean: 58 y), HbA1c (8%), BMI (26kg/m2), BNP (12pg/mL) and eGFR (84mL/min/1.73m2). Paired t-tests analyzed differences from baseline to week 52 and from week 52 to 54. Correlation analysis was performed by Pearson’s product-moment correlation coefficients. Multivariate analysis explored predictors for %ΔePV. Body weight (BW) [mean, -3kg (-5%)*; * p&amp;lt;0.01 vs. baseline], ePV (-2.7%*) and ln-transformed BNP [ln-BNP: -0.1ln(pg/mL)*] had significantly decreased by week 52. %ΔBW was not significantly correlated with %ΔePV (r=-0.06) and Δln-BNP (r=0.13) while %ΔePV was significantly correlated with Δln-BNP (r=0.35). Higher baseline ln-BNP levels were independently correlated with greater reductions in %ΔePV. After 2 weeks of withdrawal, BW [+0.9kg (+1.3%)†, † p&amp;lt;0.001 vs. week 52], ePV (+6.5%†) and ln-BNP [+0.3ln(pg/mL) †] were significantly increased. %ΔBW was significantly correlated with %ΔePV (r=0.22) and Δln-BNP (r=0.32). Also, %ΔePV was significantly correlated with Δln-BNP (r=0.30). After long-term TOFO therapy, reduced PV might be correlated not with weight loss but with reduced BNP indicating fluid loss and baseline BNP might predict changed PV. Weight gain after TOFO withdrawal might be caused by fluid gain. Disclosure Y. Matsubayashi: None. A. Yoshida: Employee; Self; Kowa Company, Ltd. T. Nojima: Employee; Self; Kowa Company, Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd. K. Fujihara: None. K. Kaku: Advisory Panel; Self; Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc. Consultant; Self; Sanwa Kagaku Kenkyusho. Research Support; Self; Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

Mediators of the effects of canagliflozin on kidney protection in patients with type 2 diabetes

Canagliflozin reduced kidney disease progression in participants with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. This analysis explored potential mediators of the effects of canagliflozin on kidney outcomes. The percent mediating effect of 18 biomarkers indicative of disease was determined by comparing the hazard ratios for the effect of randomized treatment from an unadjusted model and from a model adjusting for the average post-randomization level of each biomarker. Multivariable analyses assessed the joint effects of biomarkers that mediated most strongly in univariable analyses. The kidney outcome was defined as a composite of 40% estimated glomerular filtration rate decline, end-stage kidney disease, or death due to kidney disease. Nine biomarkers (systolic blood pressure [8.9% of effect explained], urinary albumin:creatinine ratio [UACR; 23.9%], gamma glutamyltransferase [4.1%], hematocrit [51.1%], hemoglobin [41.3%], serum albumin [19.5%], erythrocytes [56.7%], serum urate [35.4%], and urine pH [7.5%]) individually mediated the effect of canagliflozin on the kidney outcome. In a parsimonious multivariable model, erythrocyte concentration, serum urate, and systolic blood pressure maximized cumulative mediation (115%). Mediating effects of UACR, but not other mediators, were highly dependent upon the baseline level of UACR: UACR mediated 42% and 7% of the effect in those with baseline UACR 30 mg/g or more and under 30 mg/g, respectively. The identified mediators support existing hypothesized mechanisms for the prevention of kidney outcomes with sodium glucose co-transporter 2 inhibitors. Thus, the disparity in mediating effects across baseline UACR subgroups suggests that the mechanism for kidney protection with canagliflozin may vary across patient subgroups.

DCE-MRI Evaluation of 10 patients with brain metastases treated with RRx-001, a Myc inhibitor and a CD47 and PD-L1 downregulator, in a phase I/II trial called BRAINSTORM.

e14509 Background: In a Phase 1/2 trial called BRAINSTORM (NCT02215512) for brain metastases from any histology, quantitative changes in perfusion MRI after administration of RRx-001, a mic inhibitor and CD47 and PD-L1 downregulator with vascular normalizing properties, were determined and correlated with response. Methods: Ten patients with 64 total lesions evaluable at baseline, 24 hours, and end of radiotherapy (RT) that participated in BRAINSTORM were subjected to a correlative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examination four days prior to the start of whole brain radiotherapy (WBRT) that evaluated Ktrans (capillary permeability) and Vp (plasma volume). The treatment comprised RRx-001 on Day -4, pre-WBRT then twice weekly during WBRT. Four dose levels were administered (5 mg/m2, 8.4 mg/m2, 16.5 mg/m2, and 27.5 mg/m2. Results: 10 patients underwent DCE-MRI scans and eight patients with 44 total evaluable lesions had available imaging at 1 month, and 6 patients with 29 total evaluable lesions had imaging at 4 months. On univariate analysis, only a decrease in 24-hour Vp from baseline after a single dose of RRx-001 was marginally associated with absolute tumor volume response 1 month after treatment (p-0.07). In a multivariate model, only Vp prior to therapy and 24-hour change in Vp were retained in the model after stepwise selection. A reduction in Vp 24 hours after RRx-001 (prior to WBRT) was associated with reduced tumor volume at 1 month (Estimate 0.88, 95% CI 0.37-1.40, p = 0.001) and 4 months (Estimate 1.51, 95% CI 0.58-2.43, p = 0.003). Likewise, a lower Vp prior to therapy was associated with reduced tumor volume at 1 month (Estimate 0.73, 95% CI 0.29-1.17, p = 0.002) and 4 months (Estimate 1.8, 95% CI 0.95-2.65, p = 0.0002), suggesting anti-angiogenic activity and early potential vascular normalization after a single dose of RRx-001 predictive of longer-term tumor response. Conclusions: RRx-001 induced a reduction in blood plasma volume, which was associated with tumor response and which suggests a vascular normalizing effect that merits further investigation in future planned studies. Clinical trial information: NCT02215512.

Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects.

Sodium-glucose cotransporter-2 inhibitors improve heart failure-related outcomes. The mechanisms underlying these benefits are not well understood, but diuretic properties may contribute. Traditional diuretics such as furosemide induce substantial neurohormonal activation, contributing to the limited improvement in intravascular volume often seen with these agents. However, the proximal tubular site of action of the sodium-glucose cotransporter-2 inhibitors may help circumvent these limitations. Twenty patients with type 2 diabetes mellitus and chronic, stable heart failure completed a randomized, placebo-controlled crossover study of empagliflozin 10 mg daily versus placebo. Patients underwent an intensive 6-hour biospecimen collection and cardiorenal phenotyping at baseline and again after 14 days of study drug. After a 2-week washout, patients crossed over to the alternate therapy with the above protocol repeated. Oral empagliflozin was rapidly absorbed as evidenced by a 27-fold increase in urinary glucose excretion by 3 hours (P<0.0001). Fractional excretion of sodium increased significantly with empagliflozin monotherapy versus placebo (fractional excretion of sodium, 1.2±0.7% versus 0.7±0.4%; P=0.001), and there was a synergistic effect in combination with bumetanide (fractional excretion of sodium, 5.8±2.5% versus 3.9±1.9%; P=0.001). At 14 days, the natriuretic effect of empagliflozin persisted, resulting in a reduction in blood volume (-208 mL [interquartile range, -536 to 153 mL] versus -14 mL [interquartile range, -282 to 335 mL]; P=0.035) and plasma volume (-138 mL, interquartile range, -379 to 154±453 mL; P=0.04). This natriuresis was not, however, associated with evidence of neurohormonal activation because the change in norepinephrine was superior (P=0.02) and all other neurohormones were similar (P<0.34) during the empagliflozin versus placebo period. Furthermore, there was no evidence of potassium wasting (P=0.20) or renal dysfunction (P>0.11 for all biomarkers), whereas both serum magnesium (P<0.001) and uric acid levels (P=0.008) improved. Empagliflozin causes significant natriuresis, particularly when combined with loop diuretics, resulting in an improvement in blood volume. However, off-target electrolyte wasting, renal dysfunction, and neurohormonal activation were not observed. This favorable diuretic profile may offer significant advantage in the management of volume status in patients with heart failure and may represent a mechanism contributing to the superior long-term heart failure outcomes observed with these agents. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03027960.

Treinamento resistido e sistema endócrino: revisão de literatura

O treinamento resistido tem demonstrado eficácia no acréscimo e condicionamento da força muscular, devido às melhorias de aspectos neuromusculares, composição corporal, tolerância às perturbações metabólicas e aspectos endócrinos. Existe uma série de alterações endócrinas causadas pelo exercício resistido. Entretanto, poucos estudos apresentam uma relação conjunta da resposta hormonal frente ao exercício resistido. Deste modo, o objetivo desse estudo foi propor uma descrição, por meio de uma revisão bibliográfica, sobre a resposta da testosterona, GH, IGF-1 e cortisol provocado pelo exercício resistido. O presente estudo tratou-se de uma revisão bibliográfica, realizada na base de dados do Scielo, Google acadêmico, PubMed, abrangendo trabalhos nacionais e internacionais. Como critério de inclusão foi realizada uma análise para verificação dos estudos que apresentavam uma relação direta do título e resumo com a temática do trabalho aqui proposto. A excitação adrenérgica e aumento da concentração de lactato sanguíneo promove liberação de testosterona e GH. O IGF-1 é mediado pelo GH em células hepáticas e, possivelmente, por outras vias não dependente de GH. A secreção de insulina está relacionada a disponibilidade de glicose sanguínea, possuindo papel anabólico no músculo por meio da atividade da mTOR. Já a secreção de cortisol relaciona-se com a redução do volume plasmático e aumentos dos níveis de lactato. Conclui-se que, as diferentes dimensões do TR como intensidade, volume (número de séries e repetições), tipo de ação muscular (concêntrico, excêntrico, isométrico), resposta adrenérgica, volume plasmático e produção de lactato interferem diretamente sobre as concentrações hormonais plasmáticas principalmente em respostas agudas ao exercício.

Blunted Effects of Elevated Serum Osmolality on Whole‐body Heat Loss and Rectal Temperature in Middle‐aged‐to‐older Men Exercising in Dry Heat

We recently demonstrated that sweating‐induced hypohydration attenuated whole‐body heat loss (via reduced sweat evaporation) in young but not middle‐aged men during exercise‐heat stress. In that work, we reasoned that this divergent response may stem from an attenuated influence of intravascular osmolality (elevated during hypohydration) on heat dissipation in the middle‐aged. This hypothesis is supported by previous studies showing i) increased osmolality attenuates sweating in young adults and ii) fluid‐regulatory responses to osmotic stimuli are blunted with aging. However, the independent effect of intravascular osmolality on whole‐body heat loss and thermal strain in middle‐aged men during exercise has not been directly evaluated. On two separate occasions, six young (25 years [SD 4]) and eight middle‐aged‐to‐older (61 years) men underwent a 90‐min intravenous infusion of either 0.9% saline (200 [5] μmL·min−1·kg−1; ISO) or 3.0% saline (125 μmL·min−1·kg−1; HYP). Participants then performed 60 min of cycling at a fixed metabolic heat production of 250 W·m−2 in dry heat (40ºC, ~15% relative humidity). Serum osmolality and plasma volume responses were determined from venous blood samples procured at baseline (prior to infusion) and end‐exercise (60‐min). Heat production and whole‐body heat loss (evaporative + dry heat loss) were measured via indirect and direct calorimetry, respectively. Rectal temperature was monitored continuously. End‐exercise serum osmolality was elevated in HYP compared to ISO in the young (309 [4] vs 299 [3] mOsm·kg−1; p&lt;.001) and middle‐aged‐to‐older (312 [2] vs 300 [4] mOsm·kg−1; p&lt;.001) men and was similar between age‐groups (both p≥.07). In the young, the reduction in plasma volume from baseline at end‐exercise was greater in ISO relative to HYP (−8 [3] vs −4 [3]%; p=.014). By contrast, no differences in the plasma volume response were detected between ISO and HYP in the older group (−9 [4] vs −4 [6]%; p=.14). Changes in plasma volume were similar between age‐groups in each condition (both p≥.75). Whole‐body heat loss was attenuated in HYP compared to ISO in the young (233 [13] vs 251 [15] W·m−2; p=.012), whereas no effect of osmolality was observed in the middle‐aged‐to‐older men (225 [14] vs 227 [16] W·m−2; p=.74). Further, heat loss was attenuated in the middle‐aged‐to‐older vs young in ISO (p=.017) but was comparable between groups in HYP (p=.26). Similarly, a greater end‐exercise rectal temperature was noted in HYP vs ISO in the young (38.2 [0.3]°C vs 37.9 [0.3] °C; p=.037) but not the middle‐aged‐to‐older men (38.3 [0.3]°C vs 38.3 [0.3]°C; p=.88). The rectal temperature response was greater in the middle‐aged‐to‐older during ISO (p=.013) whereas no difference between age‐groups was observed in HYP (p=.59). Our findings indicate that whole‐body heat loss and rectal temperature responses to exercise in dry‐heat are not appreciably modified by increased serum osmolality in middle‐aged‐to‐older men. An age‐related reduction in osmotic sensitivity may therefore explain the blunted effect of hypohydration on heat loss previously observed in this population.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada.

BRAINSTORM: A Multi-Institutional Phase 1/2 Study of RRx-001 in Combination With Whole Brain Radiation Therapy for Patients With Brain Metastases

To determine the recommended phase 2 dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases and to assess whether quantitative changes in perfusion magnetic resonance imaging (MRI) after RRx-001 correlate with response. Five centers participated in this phase 1/2 trial of RRx-001 given once pre-WBRT and then twice weekly during WBRT. Four dose levels were planned (5 mg/m2, 8.4 mg/m2, 16.5 mg/m2, 27.5 mg/m2). Dose escalation was managed by the time-to-event continual reassessment method algorithm. Linear mixed models were used to correlate change in 24-hour T1, Ktrans (capillary permeability), and fractional plasma volume with change in tumor volume. Between 2015 and 2017, 31 patients were enrolled. Two patients dropped out before any therapy. Median age was 60 years (range, 30-76), and 12 were male. The most common tumor types were melanoma (59%) and non-small cell lung cancer (18%). No dose limiting toxicities were observed. The most common severe adverse event was grade 3 asthenia (6.9%, 2 of 29). The median intracranial response rate was 46% (95% confidence interval, 24-68) and median overall survival was 5.2 months (95% confidence interval, 4.5-9.4). No neurologic deaths occurred. Among 10 patients undergoing dynamic contrast-enhanced MRI, a reduction in Vp 24 hours after RRx-001 was associated with reduced tumor volume at 1 and 4 months (P ≤ .01). The addition of RRx-001 to WBRT is well tolerated with favorable intracranial response rates. Because activity was observed across all dose levels, the recommended phase 2 dose is 10 mg twice weekly. A reduction in fractional plasma volume on dynamic contrast-enhanced MRI 24 hours after RRx-001 suggests antiangiogenic activity associated with longer-term tumor response.

ИНТЕГРИРОВАНИЕ КОМПЛЕКСА УПРАЖНЕНИЙ ЦИГУН В МЕТОДЫ ФИЗИЧЕСКОГО ВОСПИТАНИЯ ВЫСШЕГО УЧЕБНОГО ЗАВЕДЕНИЯ

The influence of a complex of traditional qigong exercises, used in conjunction with classical methods of physical education, has been investigated in order to identify trends in changes in the indicators of general physical condition, to monitor a number of medical tests (general blood test, biochemical blood test, pulse, pressure). The work involved 619 (six hundred and nineteen) students of male main groups, of which 550 people were the experimental group and 69 were the control group. Scientific work was carried out on the basis of the Ufa State Petroleum Technical University in an annual period, from September 21, 2019 to February 20, 2020. The purpose of this study is to study the influence of this technique on increasing the level of the functional state of students, improving the process of physical education, the impact on the health of USPTU students attending classes. A similar study was described in his scientific publications by V.V. Vinantova (1996) and L.R. Kalimullina (2005). Yu.A. Petrova in her works (1992) noted that the volume of circulating blood, its components and the total number of hemoglobin increases in students under the influence of training. Metabolism is at the forefront of the changes that occur as a result of exercise. Accompanied by the released energy and the synthesis of ATP, the rate of catabolic processes in the body increases [1, 2]. The concentration of blood corpuscles increases when part of the plasma leaves the vascular bed and goes into the intercellular fluid due to physical exertion. First of all, this applies to red blood cells that transport oxygen. Under such conditions, the same volume of blood is able to carry more oxygen to working muscles [3]. The disadvantage of reducing plasma volume is an increase in blood viscosity, which makes it difficult for the heart to work. At the end of the 19th century, an increase in the number of leukocytes in the blood after exercise was found - myogenic leukocytosis. A.P. Egorov in his works (1926) showed that myogenic leukocytosis is accompanied by an increase in the number of white blood cells. The last phase may be accompanied by a sharp increase or a sharp decrease in the number of leukocytes to the physiology of the norm [4]. A change in the level of lymphocytes in the blood due to physical activity can be defined as one of the prognostic signs showing the level of adaptation of the body to physical activity

Effect on Survival of Concurrent Hemoconcentration and Increase in Creatinine During Treatment of Acute Decompensated Heart Failure

Hemoconcentration during the treatment of acute decompensated heart failure is a surrogate for plasma volume reduction and is associated with improved survival, but most definitions only allow for hemoconcentration to be determined retrospectively. An increase in serum creatinine can also be a marker of aggressive decongestion, but in isolation is not specific. Our objective was to determine if combined hemoconcentration and worsening creatinine could better identify patients that were aggressively treated and, as such, may have improved postdischarge outcomes. A total of 4,181 patients hospitalized with acute decompensated heart failure were evaluated. Those who experienced both hemoconcentration and worsening creatinine at any point had a profile consistent with aggressive in-hospital treatment and longer length of stay (p <0.01), higher loop diuretic doses (p <0.001), greater weight (p = 0.001), and net fluid loss (p <0.001) compared with the remainder of the cohort. In isolation, neither worsening creatinine (p = 0.11) nor hemoconcentration (p = 0.36) at any time were associated with improved survival. However, patients who experienced both (21%) had significantly better survival (hazard ratio 0.80, 95% confidence interval 0.69 to 0.94, pinteraction = 0.005). In conclusion, this combination of hemoconcentration and worsening creatinine, which can be determined prospectively during patient care, was associated with in-hospital parameters consistent with aggressive diuresis and improved postdischarge survival.

Plasma expanders for people with cirrhosis and large ascites treated with abdominal paracentesis.

Plasma expanders for people with cirrhosis and large ascites treated with abdominal paracentesis.

Effect of SGLT2 Inhibitors on the Sympathetic Nervous System and Blood Pressure.

Hyperactivity of sympathetic nervous system (SNS) plays a role in the development of arterial hypertension and heart failure, two co-morbidities frequently associated with type 2 diabetes (T2DM). This review aims at analyzing the effects of sodium-glucose cotransporter type 2 inhibitors (SGLT2is) on blood pressure and more especially on SNS activity in patients with T2DM. By enhancing glucosuria, natriuresis, and osmotic diuresis, SGLT2is improve glucose control, promote weight loss, lower arterial blood pressure, and reduce the risk of major cardiovascular events and hospitalization for heart failure. No rise of heart rate is detected despite reductions in blood pressure and plasma volume, which may suggest a dampening of SNS activity. Indeed, increasing experimental and clinical data demonstrated a reduction in SNS activity, including in key target organs such as the heart and the kidneys. Of potential major interest, a better understanding of the mechanisms linking SGLT2 and SNS deserves further investigation.

Cardiovascular Drift Response Over Two Different Constant-load Exercises In Healthy Non-athletes. Case Study.

Cardiovascular drift (CV-d) is a steady increase in heart rate (HR) over time while performing constant load moderate intensity exercise (CME) > 20 min. CV-d presents problems for the prescription of exercise intensity by means of HR, because the work rate (WR) during exercise must be adjusted to maintain target HR, thus disturbing the intended effect of the exercise intervention. It has been shown that the increase in HR during CME is due to changes in WR and not to CV-d. PURPOSE: We aimed to investigate whether, indeed, the CV-d in healthy young people exercising at the WR corresponding to the lactate individual anaerobic threshold (IAT) determined in two different cardiorespiratory exercise test (CPT), was related to the WR difference. METHODS: Seven participants (30 ± 3 years old, 1.75 ± 0.1 m., 74.6 ± 12.8 Kg.) performed on different days two CPT with a WR increase of 20 Watts (W) every one or three minutes until exhaustion. The WR corresponding to the IAT was determined during these tests. The participants then performed two CME with a WR corresponding to the IAT. HR and blood lactate (La) were continuously measured during all tests. A comparison between CPTs and CMEs were made using a paired t-test. A one-way ANOVA repeated measurements was used to compare La values during the CME. RESULTS: VO2max (36.9 ± 59 vs. 35.6 ± 5.7 ml·Kg-1·min-1; p > 0.05), maximal HR (181 ± 9 vs. 178 ± 11 bpm; p = 0.3), and peak La (8.7 ± 1.6 vs. 7.8 ± 1.6; p = 0.1) did not differ between CPTs. Maximal power output (271 ± 80 vs. 223 ± 75 W; p < 0.001) and WR at the IAT (164 ± 63 vs. 137 ± 45 W; p > 0.01) were different between CPTs. La between CMEs and minutes 10 and 30 were not different (3 ± 0.4 vs. 3.3 ± 0.5; p = 0.1). One-CME mean HR was 157 ± 12 bpm with an increase of 8 ± 4 bpm between minutes 10-30. Three-MCE HR was 147 ± 14 bpm and the HR increased by 9 ± 7 bpm between minute 10-30. Only a difference in HR between the two CME was found (p = 0.009) whereas there was no difference in the HR change between minute 10-30 (p = 0.7). CONCLUSION: In this case study, the CV-d was not significantly different between the two CMEs (One-IAT and Three-IAT) despite a significant difference in the amount of WR between CMEs (26 ± 19). Other factors aside from the WR like an increase in peripheral blood flow, hyperthermia, plasma volume reduction, catecholamine levels, and training status play a role in the CV-d phenomenon.

3486 Sex Differences in the Effects of Severe Food Restriction on Electrolyte Balance

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to determine if there are any sex differences in the pathophysiological effects of sFR. METHODS/STUDY POPULATION: Male Fischer rats (4-month-old) were maintained on a control (CT) (ad libitum regular chow; n=8) or sFR (60% reduction of daily food intake, n=8) diet for 2 weeks. On days 1, 2, 3 and 14, the rats were placed in metabolic cages for food and water intake and 24-hour urine collection. Body weight (BW) is measured daily. After 2 weeks, the animals are given free access to normal chow for 3 months. Short-term and long-term effects of sFR on blood pressure and heart rate will be measured. RESULTS/ANTICIPATED RESULTS: After 2 weeks, the male CT group gained 7% BW (p &lt;0.05), while BW in the sFR males was reduced by 12% (p&lt;0.05 vs. CT). In contrast, female controls did not gain BW while the sFR females lost 18% of their BW. Water intake was reduced by 35%, which was similar to the reduction in females (p=0.18). The hematocrit of sFR male rats was higher (51.1%) than the CT group (45.2%, p&lt;0.05), which was most likely due to the 6% reduction in plasma volume. A similar effect on hematocrit was observed in sRF females. Similarly, also to female rats, sFR had no effect on Na+ and K+ plasma or urine concentrations by day 14 in the male rats. DISCUSSION/SIGNIFICANCE OF IMPACT: sFR has similar effects on electrolyte balance in males and females. Ongoing studies will determine if there is any sex difference in the effects of sFR on blood pressure, heart rate and susceptibility to hypertension and cardiac injury.

Venous and autonomic function in formerly pre‐eclamptic women and controls matched for body mass index

Prepregnancy reduced plasma volume (PV) increases the risk of subsequent pre-eclamptic pregnancy. Reduced PV is thought to reflect venous reserve capacity, especially when venous vasculature is constricted and sympathetic tone is elevated. As obesity might affect these variables, and is associated with pre-eclampsia, increased body weight may underlie these observations. The aim of this study was to determine whether the relationship between reduced venous reserve and pre-eclampsia is independent of body mass index (BMI). This was an observational case-control study in which venous reserve capacity in 30 formerly pre-eclamptic, but currently non-pregnant, women divided equally into three groups based on BMI (BMI 19.5-24.9, 25.0-29.9 or ≥ 30.0kg/m2 ), was compared with that in 30 healthy parous, non-pregnant controls. Cases and controls were matched for BMI, age and parity. Venous reserve capacity was quantified by assessing PV and venous compliance (VeC). The autonomic nervous system regulating venous capacitance was evaluated using heart rate (HR) variability analysis, with the women in a resting supine position and during positive head-up tilt (HUT). Compared with controls, formerly pre-eclamptic women had, when in a resting supine position, lower PV (1339 ± 79 vs 1547 ± 139 mL/m2 (P < 0.0001)), lower VeC (0.04 ± 0.02 vs 0.07 ± 0.02 mL/dL/mmHg (P < 0.0001)), higher sympathetic tone (1.9 ± 1.1 vs 1.2 ± 0.7 (P = 0.002)) and lower baroreceptor sensitivity (BRS; 8.7 ± 3.8 vs 19.0 ± 1.7 ms/mmHg (P < 0.0001)). During HUT, women with a history of pre-eclampsia had less modulatory capacity over VeC and BRS, while HR and sympathetic tone remained consistently higher. Women with a history of pre-eclampsia had reduced venous reserve capacity compared with that in BMI-matched controls. This is reflected by lower PV and VeC, with the autonomic balance being shifted towards sympathetic dominance and lower BRS. This suggests that underlying reduced venous reserve, but not BMI, relates to pre-eclampsia. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Computer simulation of transfusion with different blood product ratios in modern massive transfusion protocols

Modern massive transfusion protocols call for early plasma and platelets to patients presenting with hemorrhagic shock. The packed red blood cell (PRBC):plasma:platelet ratio generally ranges from 1:1:1 to 3:1:1, but the ideal ratio remains controversial. We aimed to determine the effects of different resuscitation strategies and blood product ratios on hematocrit, platelet and fibrinogen concentrations (FC) during resuscitation. Assuming: pre-insult blood volume 5 L; hematocrit 0.4, FC = 100%, platelet count 400 × 109/L; predetermined constant values for each blood product unit (volume, hematocrit, FC, platelet number); and transfusion rate to maintain euvolemia, we simulated different resuscitation strategies using a computer-based hemorrhage model. When crystalloids are administered to restore an acute 30% blood loss, the initial hematocrit, platelets and FC are adequate, and remain physiologic when further resuscitation is carried out with 1:1:1. Higher transfusion ratios increase the hematocrit at the expense of proportional drops in FC and platelets. When crystalloids and PRBCs (1500 mL) are administered to restore an acute 60% blood loss, the FC drops to 39%. Further resuscitation with 1:1:1 (but not with 2:1:1 or 3:1:1) increases the FC while maintaining the hematocrit and platelets within physiologic range. When blood products (1–3:1:1) are administered to restore an acute 60% blood loss, the initial hematocrit, platelets and FC are at adequate levels, but remain within physiologic range only when 1:1:1 (but not 2:1:1 or 3:1:1) is implemented for further resuscitation. Notably, platelet concentration consistently drops in all simulated scenarios reaching dangerously low levels particularly with high blood loss/transfusion rates and with higher transfusion ratios. The FC does not always drop by the same proportion with higher ratios probably because it is based on plasma concentration and is thus “cushioned” by the reduction in plasma volume as the hematocrit rises with higher transfusion ratios. In summary, computer simulation suggests that in non-severe shock hemorrhage, the differences between 1-3:1:1 transfusion ratios during initial resuscitation may be small. In severe shock, however, 1:1:1 results in the most physiologic hematocrit, FC and platelet concentration and is, therefore, desirable.

The effect of mild decrement in plasma volume simulating short-duration spaceflight on intracranial pressure

Short-duration spaceflight induces an approximately 10% reduction in plasma volume, which leads to mild volume depletion. In a previous study, we found that mild volume depletion improved dynamic cerebral autoregulation. However, the effect of mild volume depletion on intracranial pressure (ICP) remains unknown. Therefore, we estimated ICP noninvasively (nICP), and calculated two indices relating to ICP, the cerebral artery compliance and the cerebral blood flow pulsatility index (PI), to examine whether ICP would decrease due to a mild decrement in plasma volume. In our previous experiment, fourteen subjects were administered 0.2 mg/kg of furosemide in a supine position to simulate an approximately 10% reduction in plasma volume induced by short-duration spaceflight. We re-analyzed the cerebral blood flow velocity waveform from the middle cerebral artery obtained by transcranial Doppler and the arterial blood pressure waveform at the radial artery obtained by tonometry to estimate nICP and to calculate cerebral artery compliance and PI using mathematical analysis based on an intracranial hydraulic model. All indices were compared between before and after furosemide administration. There were no significant changes in nICP and cerebral artery compliance. However, PI decreased significantly from before to after furosemide administration (0.78 ± 0.10 to 0.74 ± 0.09, p = 0.009). Decreases in ICP were not observed during the 10% reduction in plasma volume. Although cerebral artery compliance did not change, PI decreased significantly. These findings suggest that the impedance of distal cerebral arteries would be reduced in response to mild decreases in plasma volume induced by short-duration spaceflight.

Worsening renal function during decongestion among patients hospitalized for heart failure: Findings from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial

Worsening renal function (WRF) can occur throughout a hospitalization for acute heart failure (HF). However, decongestion can be measured in different ways and the prognostic implications of WRF in the setting of different measures of decongestion are unclear. Patients (N = 433) from the ESCAPE were classified by measures of decongestion during hospitalization: hemodynamic (right atrial pressure ≤8 mmHg and/or wedge pressure ≤15 mmHg at discharge), clinical (≤1 sign of congestion at discharge), hemoconcentration (any increase in hemoglobin) and estimated plasma volume using the Hakim formula (5% reduction in plasma volume). WRF was defined as creatinine increase ≥0.3 mg/dl during hospitalization. The association between WRF and 180-day all-cause death was assessed. Successful decongestion was observed in 124 (60%) patients by hemodynamics, 204 (49%) by clinical exam, 173 (47%) by hemoconcentration, and 165 (45%) by plasma volume. There was no agreement between the hemodynamic assessment and other decongestion measures in up to 43% of cases. Persistent congestion with concomitant WRF at discharge was associated with worse outcomes compared to patients without congestion and WRF. Among patients decongested at discharge, in-hospital WRF was not significantly associated with 180-day all-cause death, when using hemodynamic, clinical or estimated plasma volume as measures of decongestion (P > .05 for all markers). In patients hospitalized for HF, although there was disagreement across common measures of decongestion, in-hospital WRF was not associated with increased hazard of all-cause mortality among patients successfully decongested at discharge.