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1.
Insulin-mediated muscle microvascular perfusion and its phenotypic predictors in humans.
Love, KM, Jahn, LA, Hartline, LM, Patrie, JT, Barrett, EJ, Liu, Z
Scientific reports. 2021;(1):11433
Abstract
Insulin increases muscle microvascular perfusion and enhances tissue insulin and nutrient delivery. Our aim was to determine phenotypic traits that foretell human muscle microvascular insulin responses. Hyperinsulinemic euglycemic clamps were performed in 97 adult humans who were lean and healthy, had class 1 obesity without comorbidities, or controlled type 1 diabetes without complications. Insulin-mediated whole-body glucose disposal rates (M-value) and insulin-induced changes in muscle microvascular blood volume (ΔMBV) were determined. Univariate and multivariate analyses were conducted to examine bivariate and multivariate relationships between outcomes, ΔMBV and M-value, and predictor variables, body mass index (BMI), total body weight (WT), percent body fat (BF), lean body mass, blood pressure, maximum consumption of oxygen (VO2max), plasma LDL (LDL-C) and HDL cholesterol, triglycerides (TG), and fasting insulin (INS) levels. Among all factors, only M-value (r = 0.23, p = 0.02) and VO2max (r = 0.20, p = 0.047) correlated with ΔMBV. Conversely, INS (r = - 0.48, p ≤ 0.0001), BF (r = - 0.54, p ≤ 0.001), VO2max (r = 0.5, p ≤ 0.001), BMI (r = - 0.40, p < 0.001), WT (r = - 0.33, p = 0.001), LDL-C (r = - 0.26, p = 0.009), TG (r = - 0.25, p = 0.012) correlated with M-value. While both ΔMBV (p = 0.045) and TG (p = 0.03) provided significant predictive information about M-value in the multivariate regression model, only M-value was uniquely predictive of ΔMBV (p = 0.045). Thus, both M-value and VO2max correlated with ΔMBV but only M-value provided unique predictive information about ΔMBV. This suggests that metabolic and microvascular insulin responses are important predictors of one another, but most metabolic insulin resistance predictors do not predict microvascular insulin responses.
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2.
Early MRI Blood Volume Changes in Constrictor Muscles Correlate With Postradiation Dysphagia.
Mierzwa, ML, Gharzai, LA, Li, P, Wilkie, JR, Hawkins, PG, Aryal, MP, Lee, C, Rosen, B, Lyden, T, Blakely, A, et al
International journal of radiation oncology, biology, physics. 2021;(2):566-573
Abstract
PURPOSE Predicting individual patient sensitivity to radiation therapy (RT) for tumor control or normal tissue toxicity is necessary to individualize treatment planning. In head and neck cancer, radiation doses are limited by many nearby critical structures, including structures involved in swallowing. Previous efforts showed that imaging parameters correlate with RT dose; here, we investigate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) blood volume (BV) changes in predicting dysphagia. METHODS AND MATERIALS This study included 32 patients with locally advanced oropharyngeal squamous cell carcinoma treated with definitive chemoradiation on an institutional protocol incorporating baseline and early midtreatment DCE-MRI. BV maps of the pharyngeal constrictor muscles (PCM) were created, and BV increases midtreatment were correlated with the following parameters at 3 and 12 months post-RT: RT dose, Dynamic Imaging Grade of Swallowing Toxicity swallow score, aspiration frequency, European Organisation for Research and Treatment of Cancer HN35 patient-reported outcomes, physician-reported dysphagia, and feeding tube (FT) dependence. RESULTS The mean BV to the PCMs increased from baseline to fraction 10, which was significant for the superior PCM (P = .006) and middle PCM (P < .001), with a trend in the inferior PCM where lower mean doses were seen (P = .077). The factors associated with FT dependence at 3 months included BV increases in the total PCM (correlation, 0.48; P = .006) and middle PCM (correlation, 0.50; P = .004). A post-RT increase in aspiration was associated with a BV increase in the superior PCM (correlation, 0.44; P = .013),and the increase in the total PCMs was marginally significant (correlation, 0.34; P = .06). The best-performing models of FT dependence (area under the receiver operating curve [AUC] = 0.84) and aspiration increases (AUC = 0.78) included BV increases as well as a mean RT dose to middle PCM. CONCLUSIONS Our results suggest that midtreatment BV increases derived from DCE-MRI are an early predictor of dysphagia. Further investigation of these promising imaging markers to assess individual patient sensitivity to treatment and the patient's subsequent risk of toxicities is warranted to improve personalization of RT planning.
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3.
A randomized, controlled, double-blind crossover study on the effects of isoeffective and isovolumetric intravenous crystalloid and gelatin on blood volume, and renal and cardiac hemodynamics.
Bradley, CR, Bragg, DD, Cox, EF, El-Sharkawy, AM, Buchanan, CE, Chowdhury, AH, Macdonald, IA, Francis, ST, Lobo, DN
Clinical nutrition (Edinburgh, Scotland). 2020;(7):2070-2079
Abstract
BACKGROUND & AIMS Blood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output. METHODS Healthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging. RESULTS Ten of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index. CONCLUSIONS A smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid. TRIAL REGISTRATION The protocol was registered with the European Union Drug Regulating Authorities Clinical Trials Database (https://eudract.ema.europa.eu) (EudraCT No. 2013-003260-32).
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4.
Obesity in pregnancy causes a volume overload in third trimester.
Vonck, S, Lanssens, D, Staelens, AS, Tomsin, K, Oben, J, Bruckers, L, Gyselaers, W
European journal of clinical investigation. 2019;(11):e13173
Abstract
BACKGROUND Obesity is a major risk factor for cardiovascular diseases. In this study, we aimed to investigate the maternal circulatory differences during pregnancy between obese and normal weight women. MATERIALS AND METHODS The functioning of the maternal circulation (arteries, veins, heart and body fluid) was assessed by ECG-Doppler ultrasound, impedance cardiography (ICG) and bio-impedance during pregnancy in obese women (BMI ≥30 kg/m2 ) and normal weight, nonobese women (BMI 20-25 kg/m2 ). In this observational study, 232 assessments were performed in the obese group, whereas 919 assessments were performed in the nonobese group. RESULTS Relative to nonobese women, the overall cardiovascular function in obese women during first and second trimester is consistent with a high volume/low-resistance circulation. In third trimester, cardiac output of obese women decreases from 9.2 (8.2-10.7) L/min to 8.5 (7.6-9.6) L/min (P = .037) whereas this is not true in the nonobese women (from 7.8 (7-8.5) L/min to 7.8 (6.8-8.9) L/min, P = .536). Simultaneously, the persistently lower peripheral vascular resistance in obese vs nonobese women disappears (880 (761-1060) dyn.sec/cm5 vs 928 (780-1067). CONCLUSIONS The circulatory gestational adaptations between nonobese and obese women were generally similar. The findings in the third trimester suggest that a pregnancy in obese women start as a state of high volume/low resistance, gradually shifting to a volume overload with decrease of cardiac output and disappearance of low vascular resistance. This evolution makes obese women vulnerable for gestational hypertensive diseases.
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5.
Applied Physiology of Fluid Resuscitation in Critical Illness.
Arshed, S, Pinsky, MR
Critical care clinics. 2018;(2):267-277
Abstract
Fluids during resuscitation from shock increase mean systemic pressure and venous return. The pressure gradient for venous return must increase. Mean systemic pressure is the amount of vascular space in unstressed and stressed volume, mostly unstressed. Shock states can decrease mean systemic pressure by increasing unstressed volume, decreasing total blood volume, or decreasing the pressure gradient for venous return. Crystalloids across bodily spaces restore normal volume, whereas colloids remain in the intravascular space. Electrolyte content of fluids matters and excess chloride impairs renal blood flow. Albumin seems to be more effective at restoring blood volume in severe sepsis, but not in other conditions.
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6.
Subclinical volume overload in stable outpatients with chronic heart failure.
Boonen, L, Verbrugge, FH, Nijst, P, Noyens, P, De Vusser, P, Verhaert, D, Van Lierde, J, Vrolix, M, Dupont, M, Mullens, W
Acta cardiologica. 2016;(3):299-307
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7.
An alternative hypothesis to the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension.
Kurtz, TW, DiCarlo, SE, Pravenec, M, Schmidlin, O, Tanaka, M, Morris, RC
Kidney international. 2016;(5):965-973
Abstract
It is widely held that in response to high salt diets, normal individuals are acutely and chronically resistant to salt-induced hypertension because they rapidly excrete salt and retain little of it so that their blood volume, and therefore blood pressure, does not increase. Conversely, it is also widely held that salt-sensitive individuals develop salt-induced hypertension because of an impaired renal capacity to excrete salt that causes greater salt retention and blood volume expansion than that which occurs in normal salt-resistant individuals. Here we review results of both acute and chronic salt-loading studies that have compared salt-induced changes in sodium retention and blood volume between normal subjects (salt-resistant normotensive control subjects) and salt-sensitive subjects. The results of properly controlled studies strongly support an alternative view: during acute or chronic increases in salt intake, normal salt-resistant subjects undergo substantial salt retention and do not excrete salt more rapidly, retain less sodium, or undergo lesser blood volume expansion than do salt-sensitive subjects. These observations: (i) directly conflict with the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension, and (ii) have implications for contemporary understanding of how various genetic, immunologic, and other factors determine acute and chronic blood pressure responses to high salt diets.
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8.
A randomized, controlled, double-blind crossover study on the effects of 1-L infusions of 6% hydroxyethyl starch suspended in 0.9% saline (voluven) and a balanced solution (Plasma Volume Redibag) on blood volume, renal blood flow velocity, and renal cortical tissue perfusion in healthy volunteers.
Chowdhury, AH, Cox, EF, Francis, ST, Lobo, DN
Annals of surgery. 2014;(5):881-7
Abstract
OBJECTIVE We compared the effects of intravenous administration of 6% hydroxyethyl starch (maize-derived) in 0.9% saline (Voluven; Fresenius Kabi, Runcorn, United Kingdom) and a "balanced" preparation of 6% hydroxyethyl starch (potato-derived) [Plasma Volume Redibag (PVR); Baxter Healthcare, Thetford, United Kingdom] on renal blood flow velocity and renal cortical tissue perfusion in humans using magnetic resonance imaging. BACKGROUND Hyperchloremia resulting from 0.9% saline infusion may adversely affect renal hemodynamics when compared with balanced crystalloids. This phenomenon has not been studied with colloids. METHODS Twelve healthy adult male subjects received 1-L intravenous infusions of Voluven or PVR over 30 minutes in a randomized, double-blind manner, with crossover studies 7 to 10 days later. Magnetic resonance imaging proceeded for 60 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion. Blood was sampled, and weight was recorded at 0, 30, 60, 120, 180, and 240 minutes. RESULTS Mean peak serum chloride concentrations were 108 and 106 mmol/L, respectively, after Voluven and PVR infusion (P = 0.032). Changes in blood volume (P = 0.867), strong ion difference (P = 0.219), and mean renal artery flow velocity (P = 0.319) were similar. However, there was a significant increase in mean renal cortical tissue perfusion after PVR when compared with Voluven (P = 0.033). There was no difference in urinary neutrophil gelatinase-associated liopcalin to creatinine ratios after the infusion (P = 0.164). CONCLUSIONS There was no difference in the blood volume-expanding properties of the 2 preparations of 6% hydroxyethyl starch. The balanced starch produced an increase in renal cortical tissue perfusion, a phenomenon not seen with starch in 0.9% saline.
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9.
Phlebotomy eliminates the maximal cardiac output response to six weeks of exercise training.
Bonne, TC, Doucende, G, Flück, D, Jacobs, RA, Nordsborg, NB, Robach, P, Walther, G, Lundby, C
American journal of physiology. Regulatory, integrative and comparative physiology. 2014;(10):R752-60
Abstract
With this study we tested the hypothesis that 6 wk of endurance training increases maximal cardiac output (Qmax) relatively more by elevating blood volume (BV) than by inducing structural and functional changes within the heart. Nine healthy but untrained volunteers (Vo2max 47 ± 5 ml·min(-1)·kg(-1)) underwent supervised training (60 min; 4 times weekly at 65% Vo2max for 6 wk), and Qmax was determined by inert gas rebreathing during cycle ergometer exercise before and after the training period. After the training period, blood volume (determined in duplicates by CO rebreathing) was reestablished to pretraining values by phlebotomy and Qmax was quantified again. Resting echography revealed no structural heart adaptations as a consequence of the training intervention. After the training period, plasma volume (PV), red blood cell volume (RBCV), and BV increased (P < 0.05) by 147 ± 168 (5 ± 5%), 235 ± 64 (10 ± 3%), and 382 ± 204 ml (7 ± 4%), respectively. Vo2max was augmented (P < 0.05) by 10 ± 7% after the training period and decreased (P < 0.05) by 8 ± 7% with phlebotomy. Concomitantly, Qmax was increased (P < 0.05) from 18.9 ± 2.1 to 20.4 ± 2.3 l/min (9 ± 6%) as a consequence of the training intervention, and after normalization of BV by phlebotomy Qmax returned to pretraining values (18.1 ± 2.5 l/min; 12 ± 5% reversal). Thus the exercise training-induced increase in BV is the main mechanism increasing Qmax after 6 wk of endurance training in previously untrained subjects.
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10.
Modeling of change in blood volume and extracellular fluid volume during hemodialysis.
Zhu, F, Kappel, F, Leonard, EF, Kotanko, P, Levin, NW
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference. 2013;:1506-9
Abstract
Knowledge of dynamics of shift of fluid volume between intra- and extravascular compartments during hemodialysis (HD) is important for managing HD treatment to help patients approach dry weight without hypotension. The Relative blood volume (RBV) monitor indicates change in plasma volume based on the difference between ultrafiltration rate (UFR) and plasma refilling rate (PRR) during HD. However, the absolute value of PRR cannot be obtained from RBV. The aim of this study was to investigate whether fluid transport from the interstitial to blood spaces can be quantitatively analyzed with a two compartments model. 14 patients (30 measurements) were studied. RBV using a blood volume monitor (BVM, Fresenius) and calf extracellular volumes (ECV) by calf bioimpedance device (Hydra 4200, Xitron) were continuously measured during HD. A mathematic model was established with unknown transport coefficients (k1, k2, α, β, γ, δ) and these coefficients were estimated using a Least Squares Optimization algorithm by fitting from experimental data. A high correlation (R(2)>0.8) between experimental data and calculation by the model were observed in both RBV and ECV measurements. Coefficients k1 and δ significantly differed with different degree of hydration. This model provides parameters which can used to understand relationships between degree of hydration and refilling rate.