Reduction In Blood Volume Research Articles

LITERATUR REVIEW: MENGKAJI EFEKTIVITAS PEMBERIAN MENTIMUN TERHADAP PENURUNAN TEKANAN DARAH

Introduction: Hypertension is a degenerative disease. Those aged ?55 years are at risk for suffering from hypertension, previously blood pressure prehypertension before being diagnosed with hypertension occurred between the third and fifth decades. The World Health Organization reports as many as 839 million cases of hypertension, by 2025 this figure is expected to increase to 1.15 billion or around 29% of the world's total population, where female sufferers are more than 30% compared to male hypertension sufferers, namely 29%. One of the non-pharmacological treatments to treat hypertension is consuming cucumber. Methods: International and national literature searched through electronic media with keyword hints. Eight articles were selected, each of which represents an effectiveness of giving cucumber to reduce blood pressure and provides various information. Results: There was an effect of giving cucumber on reducing blood pressure in respondents. Discussion: One alternative that can be used to lower blood pressure is by consuming cucumber. The diuretic effect on cucumber causes the salt content in the blood to decrease. Reduced levels of salt that absorbs or retains water will reduce blood volume so that it can lighten the work of the heart in pumping blood, and eventually blood pressure will decrease. Conclusion: The conclusion based on the analysis that has been done is that cucumber is effective for lowering blood pressure.

Letter to the Editor: The Concept of Real‐Time Spectroscopy for Liver Viability Assessment

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest the article by Ember et al., where the investigators explored the value of Raman spectroscopy to assess liver viability in a porcine model donated after circulator death (DCD) with subsequent normothermic regional perfusion (NRP).(1) The microvascular environment was analyzed through real‐time stimulated Raman spectroscopy (SRS) and histology. Trapped erythrocytes were quantified in ischemic liver areas through the intrinsic Raman signal of hemoglobin (excitation wavelength, 532 nm).(1) The investigators found a reduction of liver congestion with less red blood cells, stuck in the sinusoids after NRP. Removal of 10% of donor blood before treatment withdrawal and circulatory death was found to be protective and resulted in healthier sinusoids with less congestion.(1) Although the article targets the hot topic of viability assessment, a few points require clarification. The investigators suggest a reduction of donor blood volume before organ donation, to decrease organ injury for transplantation. However, any donor pretreatment, including heparin administration, before withdrawal of all supportive measures, is strictly prohibited in many countries. Following treatment withdrawal, DCD donors deteriorate until circulatory death occurs, with a subsequent mandatory stand‐off period (2‐30 minutes) worldwide. Super‐rapid donor laparotomy and cannulation with cold flush or NRP are only started after donor death confirmation. Any measures, which may accelerate natural donor deterioration, including a reduction of blood volume, is therefore a violation of the donation protocol. During combined thoracic‐abdominal DCD organ procurement, the donor blood, used for normothermic ex situ heart perfusion, is obtained after circulatory death.(2) Next, although we agree that a healthy microvasculature is important, it is only one contributor to liver viability, which should target the key players of liver function: mitochondria. Ischemia leads here to metabolite accumulation and energy loss.(3) At reperfusion, reactive oxygen species and flavin mononucleotides (FMNs) are released from mitochondrial complex‐I.(4) Additionally, this autofluoresecent, mitochondrial FMN can be easily quantified from various perfusates by real‐time fluorescence spectroscopy, as recently demonstrated during hypothermic oxygenated perfusion (HOPE; Fig. 1).(4) FMN concentration in HOPE perfusates has a high predictive accuracy for graft loss and posttransplant complications and was validated by mass spectometry.(5)FIG. 1: Real‐time spectroscopy for viability assessment before liver transplantation. Real‐time viability tests are currently a hot topic in solid organ transplantation. Various spectroscopic techniques are explored on tissues and perfusates. Donor and graft assessment is a staged procedure and involves multiple unspecific tests performed from donor to recipient center.( 1‐3 ) Fluorescence spectroscopy is a valuable tool for viability assessment from perfusates, obtained during machine perfusion. Mitochondrial molecules, including FMN, are released during reoxygenation of human tissue and represent mitochondrial function and injury to predict outcomes after transplantation of high‐risk donor organs.( 4 )In summary, various spectroscopic techniques are currently tested as important tools for future viability assessment. Author Contributions M.F.C., A.S.: Conception and design. M.F.C.: Acquisition of data. M.F.C., A.S.: Analysis and interpretation of data. M.F.C.: Drafting of the article. P.M., P.D., A.S.: Critical revision for important intellectual content. M.F.C., M.M., P.M., P.D., A.S.: Final approval of the published version.

Effect of Intradialytic Aerobic Exercise on Relative Blood Volume in Patients Undergoing Maintenance Hemodialysis.

The purpose of this study was to investigate changes in the relative blood volume because of intradialytic exercise. Twenty patients undergoing hemodialysis (HD) were assigned randomly to exercise or control sessions as a first test by simple randomization. All participants were crossed over and participated in both tests. In the exercise test, each patient underwent 30 minutes of exercise using a cycle ergometer from the initiation of HD. The control session consisted of routine HD without exercise. The blood volume (ΔBV) reduction in both types of sessions was calculated from the area under the curve of the ΔBV (ΔBVAUC) from the initiation of HD to the end of exercise (During Ex), from the end of exercise to the end of HD (Post Ex), and during the entire HD session (Whole HD). The ΔBVAUC of Post Ex in the exercise test (44.9 ± 14.3%h) was significantly smaller than that in the control test (50.3 ± 14.3%h) (p < 0.05), although other parameters such as ΔBVAUC either in the entire HD session or during exercise training did not differ significantly between two groups. This result suggests that intradialytic exercise at the beginning of the HD sessions may be altered the ΔBV in the latter part of the session.

Effect of Exercise-Induced Reductions in Blood Volume on Cardiac Output and Oxygen Transport Capacity.

We wanted to demonstrate the relationship between blood volume, cardiac size, cardiac output and maximum oxygen uptake (O2max) and to quantify blood volume shifts during exercise and their impact on oxygen transport. Twenty-four healthy, non-smoking, heterogeneously trained male participants (27 ± 4.6 years) performed incremental cycle ergometer tests to determine O2max and changes in blood volume and cardiac output. Cardiac output was determined by an inert gas rebreathing procedure. Heart dimensions were determined by 3D echocardiography. Blood volume and hemoglobin mass were determined by using the optimized CO-rebreathing method. The O2max ranged between 47.5 and 74.1 mL⋅kg–1⋅min–1. Heart volume ranged between 7.7 and 17.9 mL⋅kg–1 and maximum cardiac output ranged between 252 and 434 mL⋅kg–1⋅min–1. The mean blood volume decreased by 8% (567 ± 187 mL, p = 0.001) until maximum exercise, leading to an increase in [Hb] by 1.3 ± 0.4 g⋅dL–1 while peripheral oxygen saturation decreased by 6.1 ± 2.4%. There were close correlations between resting blood volume and heart volume (r = 0.73, p = 0.002), maximum blood volume and maximum cardiac output (r = 0.68, p = 0.001), and maximum cardiac output and O2max (r = 0.76, p < 0.001). An increase in maximum blood volume by 1,000 mL was associated with an increase in maximum stroke volume by 25 mL and in maximum cardiac output by 3.5 L⋅min–1. In conclusion, blood volume markedly decreased until maximal exhaustion, potentially affecting the stroke volume response during exercise. Simultaneously, hemoconcentrations maintained the arterial oxygen content and compensated for the potential loss in maximum cardiac output. Therefore, a large blood volume at rest is an important factor for achieving a high cardiac output during exercise and blood volume shifts compensate for the decrease in peripheral oxygen saturation, thereby maintaining a high arteriovenous oxygen difference.

Nutritional status and volume control in adolescents on chronic hemodialysis.

Pediatric patients on maintenance hemodialysis (HD) are at risk of both malnutrition and fluid overload. This pilot study aimed to assess correlates of normalized protein catabolic rate (nPCR) in adolescents on chronic HD, in particular fluid status markers. All patients aged 10-18 years on chronic HD in our center between 2017 and 2019 were enrolled. For each patient, mean nPCR was calculated and correlations with the following parameters investigated: dry body weight change in subsequent 3 months in kg (∆BW) and percentage of BW (∆BW%), change in body mass index (∆BMI), preHD systolic and diastolic blood pressure (SBP, DBP), residual urine output, biochemistry, and blood volume monitoring-derived first hour refill index (RI), calculated as ratio between ultrafiltration rate and reduction in relative blood volume in first hour of dialysis. Seventy-nine nPCR determinations were collected in 23 patients, median age 14.8 years. nPCR significantly correlated with ∆BW, ∆BW%, ∆BMI, spKT/V, and preHD serum creatinine, and negatively correlated with age, DBP SDS (r=-0.466, p=0.025) and RI (r=-0.435, p=0.043). RI was significantly higher in patients with nPCR <1 than those with nPCR above this threshold: 3.2 (1.9-4.7) vs. 1.4 (0.7-1.8) ml/kg/h/% (p=0.021). At multivariable analysis, nPCR remained positively correlated with creatinine and spKt/V, and inversely correlated with RI. nPCR is a significant predictor of weight change in adolescents on maintenance HD, and seems associated with creatinine and dialysis adequacy. Inverse correlation with RI suggests possible associations between malnutrition and fluid overload, but larger prospective studies are needed to confirm this. A higher resolution version of the Graphical abstract is available as Supplementary information.

Monitoring relative blood volume changes during hemodialysis: Impact of the priming procedure.

The monitoring of relative blood volume (RBV) changes during hemodialysis is increasingly used to evaluate the effect of dialyzer ultrafiltration on intravascular volume to guide the removal of excess fluid in a manner that maintains hemodynamic stability of the patient. RBV monitoring is typically based on an optical or acoustic sensor placed in the arterial blood line that measures a marker of hemoconcentration, such as hematocrit, hemoglobin, or total blood protein. However, the accuracy of RBV monitors and the impact of their clinical use remain the subject of ongoing debate. Here, we show that, depending on the procedure of filling the extracorporeal circuit with the patient's blood at the beginning of the dialysis session, theindications of an RBV monitor may be misleading as to the actual changes of the intravascular volume. When the blood is first pumped into the dialyzer, the priming fluid (saline) that fills the circuit may be either infused into the patient or disposed of to a drain bag. In the latter case, the intravascular volume is suddenly reduced, which is not accounted for by RBV monitors that track only the subsequent reductions in blood volume due to dialyzer ultrafiltration. Weanalyzed this general aspect of RBV monitoring using model-based simulations and showed quantitatively how RBV changes calculated using hematocrit differ depending on the priming procedure.

Effects of Blood Withdrawal on Cardiac, Hemodynamic, and Pulmonary Responses to a Moderate Acute Workload in Healthy Middle‐Aged and Older Females

Background The fundamental role of blood volume (BV) on cardiorespiratory fitness has been well studied in males during maximal exercise. However, understanding the importance of BV on key physiological responses to a submaximal workload in females has yet to be elucidated. The objective of this study was to investigate the effects of blood withdrawal on cardiac, hemodynamic, and pulmonary responses to submaximal exercise in females. We hypothesized that blood withdrawal would reduce cardiac filling and stroke volume (SV) which would result in a compensatory increase in heart rate (HR) to preserve cardiac output (Q) at a fixed submaximal workload. Methods 30 healthy females (63.8 ± 8.3 yr) were recruited for this study. Transthoracic echocardiography, non-invasive blood pressure monitoring, and a peak oxygen uptake (VO2peak) test were performed at a 100 W submaximal workload prior to and immediately after a 10 % reduction of BV. Primary outcomes included left ventricular end-diastolic volume (LVEDV), SV, Q, HR, and VO2peak. BV was determined using an established carbon monoxide rebreathing technique. Results BV of subjects ranged from 3.8 to 6.6 L, with an average 10 % reduction of 0.5 ± 0.1 L. Following blood withdrawal, both LVEDV (P ≤ 0.030) and SV (P < 0.019) were reduced while Q was unchanged (P = 0.139) due to an augmented HR (P < 0.026). Submaximal hemodynamic variables including MAP (P < 0.015), SBP (P < 0.005), and DBP (P < 0.038) were reduced while VO2peak was unaltered (P = 0.250). Conclusion Blood withdrawal results in marked reductions in cardiac filling with compensatory chronotropic responses that preserve Q at an acute moderate submaximal workload in healthy females. BV thus determines the relative exercise intensity, as typically determined by HR, of submaximal efforts in this population.

The design and use of a simple device for the MRI assessment of changes in cardiovascular function by lower-body negative-pressure-simulated reduction of central blood volume

To use a locally designed and simple lower-body negative-pressure (LBNP) device and 1.5 T magnetic resonance imaging (MRI) to demonstrate the ability to assess changes in cardiovascular function during preload reduction. These effects were evaluated on ventricular volumes and great vessel flow in healthy volunteers, for which there are limited published data. After ethical review, 14 volunteers (mean age 33.9±7 years, mean body mass index [BMI] 23.1±2.5) underwent LBNP prospectively at 0, -5, -10, and -20 mmHg pressure, using a locally designed LBNP box. Expiratory breath-hold biventricular volumes, and free-breathing flow imaging of the ascending aorta and main pulmonary artery were acquired at each level of LBNP. At -5 mmHg, there was no change in aortic flow or left ventricular volumes versus baseline. Right ventricular output (p=0.013) and pulmonary net flow (p=0.026) decreased. At -20 mmHg, aortic and pulmonary net flow (p<0.001) decreased, as were left and right ventricular end diastolic volume (p<0.001) and left and right end systolic volumes (p=0.038 and p=0.003 respectively). Use of a MRI-compatible LBNP device is feasible to measure changes in ventricular volume and great arterial flow in the same experiment. This may enhance further research into the effects of preload reduction by MRI in a wide range of important cardiovascular pathologies.

Tiny Bodies, Big Needs: Prospective Biobanking of Neonatal Clinical Remnant Samples.

Repurposing biological samples collected for required diagnostic purposes into suitable biobanking projects is a particularly useful method for enabling research in vulnerable populations. This approach is especially appropriate for the neonate in the neonatal intensive care unit (NICU), where blood volume reductions can quickly increase beyond minimal risk for adverse events, such as iatrogenic anemia, and proxy consent provided by parents or guardians is required. The method described in this study provides a framework to prospectively collect and store blood-derived clinical samples after all clinical and regulatory requirements are fulfilled. The consent approach incorporated a 30-day window to allow parents and guardians ample consideration time with follow-up involvement with NICU embedded study team members. The study enrolled 875 participants over a 3-year period. This established a critically needed biobank to support investigator-initiated research with explicit study aims requiring samples at defined day of life frequencies within the NICU and created a normative control reference bank for case comparisons for premature and full-term neonates with brain injury.

Quantitative fluorescence angiography detects dynamic changes in gastric perfusion.

The use of Indocyanine green (ICG) fluorescence angiography (ICG-FA) is an applied method to assess visceral perfusion during surgical procedures worldwide. Further development has entailed quantification of the fluorescence signal; however, whether quantified ICG-FA can detect intraoperative changes in perfusion after hemorrhage has not been investigated previously. In this study, we investigated whether a quantification method, developed and validated in our department (q-ICG), could detect changes in gastric perfusion induced by hemorrhage and resuscitation. Ten pigs were included in the study. Specific regions of interest of the stomach were chosen, and three q-ICG measurements of gastric perfusion obtained: 20min after completion of the laparoscopic setup (baseline), after reducing the circulating blood volume by 30%, and after reinfusion of the withdrawn blood volume. Hemodynamic variables were recorded, and blood samples were collected every 10min during the procedure. The reduction in blood volume generated decreased gastric perfusion (q-ICG) from baseline (p = 0.023), and gastric perfusion subsequently increased (p < 0.001) after the reintroduction of the withdrawn blood volume. Cardiac output (CO) and mean arterial blood pressure (MAP) shifted correspondingly and the gastric perfusion correlated to CO (r = 0.575, p = 0.001) and MAP (r = 0.436, p = 0.018). We present a novel study showing that the q-ICG method can detect dynamic changes in local tissue perfusion induced by hemorrhage and resuscitation. As regional gastrointestinal perfusion may be significantly reduced, while hemodynamic variables such as MAP or heart rate remain stable, q-ICG may provide an objective, non-invasive method for detecting regional early ischemia, strengthening surgical decision making.

Hypertension Profile of Angiotensin Receptor Blocker From Matoa Leaves Extract (Pometia Pinnata J.R. Foster & G. Foster) In Angiotensin II Induced-Male Rat With Blood Volume Parameter

Hypertension is a problem of cardiovascular disease that occurs in many people. The leaves of matoa, which have another name, Pometia pinnata, are one of the plants used as traditional medicine for the treatment of hypertension. The active compounds of matoa leaves are flavonoids. This study aimed to observe the hypertension profile of the Angiotensin Receptor Blocker class. The test animals used in this study were 45 male Wistar rats. Each group consisted of 5 rats induced by angiotensin II, divided into groups, namely normal control, negative control, positive control, a dose of 75g/kgBW, 150g/kgBW, and 300g/kgBW, and observation were done for 14 days. The hypertension profile observed in this study was the blood volume of rats. The percentage reduction in blood volume of rats given the best matoa leaves extract was 300 mg/kgBW, extract which showed mean difference in negative control group with a significance value of <0.05

The influence of rosella flower tea on blood pressure reduction in hypertension patients

Background: Hypertension is called the silent killer because it does not provide specific symptoms, it can increase the incidence of strokes, heart attacks, chronic kidney disease if not controlled and controlled properly. Management of hypertension is generally with pharmacological therapy that has not shown improvement. Non-pharmacological treatment using rosella flower tea which functions to open blood vessels wider, reduce blood viscosity and increase urine production so as to reduce blood volume. The purpose of this study was to study the effect of rosella tea on reducing blood pressure in hypertensive patients. Methods: This study uses a quasi-experiment design with the two-group pre-test and post-test design approach. This research was conducted on patients with hypertension at the Padang city health center with an intervention group of 16 respondents and a control of 16 respondents. Data analysis in this study used univariate and bivariate using independent t-test statistics. Results: The results of the study showed the average blood pressure in the systolic pretest intervention group 147.81 for 94.69 diastole and posttest systole 129.06 posttest diastole 78.75 while the control group for systole pretest 154.6 for diastole 96.25 and posttest without posttest treatment systole 129.06 postest diastole 78.75. Obtained a p value 0,000 statistical test for systole and a p value 0,000 diastole. Conclusions: There is an effect of rosella flower tea on reducing blood pressure in patients with hypertension at the Padang city health center.

Predicted Cardiac Hemodynamic Consequences of the Renal Actions of SGLT2i in the DAPA-HF Study Population: A Mathematical Modeling Analysis.

The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study demonstrated that dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), reduced heart failure hospitalization and cardiovascular death in patients with heart failure with reduced ejection fraction (HF-rEF), with and without type 2 diabetes mellitus. Multiple potential mechanisms have been proposed to explain this benefit, which may be multifactorial. This study aimed to quantify the contribution of the known natriuretic/diuretic effects of SGLT2is to changes in cardiac hemodynamics, remodeling, and fluid homeostasis in the setting of HF-rEF. An integrated cardiorenal mathematical model was used to simulate inhibition of SGLT2 and its consequences on cardiac hemodynamics in a virtual population of HF-rEF patients generated by varying model parameters over physiologically plausible ranges and matching to baseline characteristics of individual DAPA-HF trial patients. Cardiovascular responses to placebo and SGLT2i over time were then simulated. The baseline characteristics of the HF-rEF virtual population and DAPA-HF were in good agreement. SGLT2i-induced diuresis and natriuresis that reduced blood volume and interstitial fluid volume, relative to placebo within 14 days. This resulted in decreased left ventricular end-diastolic volume and pressure, indicating reduced cardiac preload. Thereafter, blood volume and interstitial fluid volume again began to accumulate, but pressures and volumes remained shifted lower relative to placebo. After 1 year, left ventricle mass was lower and ejection fraction was higher than placebo. These simulations considered only hemodynamic consequences of the natriuretic/diuretic effects of SGLT2i, as other mechanisms may contribute additional benefits besides those predictions.

Hemodialysis crossover study using a relative blood volume change-guided ultrafiltration control compared with standard hemodialysis: the BV-UFC study

BackgroundIt has been difficult to sufficiently achieve body-fluid management using blood volume (BV) monitor during hemodialysis (HD) with constant ultrafiltration (UF) rate. Recently, a relative BV change-guided UF control (BV-UFC) system was developed by combining the concepts of an automatic feedback system that could control the UF rate and profile with real- time monitoring of relative changes in BV (%ΔBV). However, this system has limited application in the clinical setting. Therefore, in this study, we aimed to perform the crossover study on HD with BV-UFC compared to standard HD in terms of hemodynamic stability during HD.MethodsForty-eight patients entered an 8-week crossover period of standard HD or HD with BV-UFC. Prevalence of intradialytic hypotension (IDH) as a primary outcome and changes in blood pressure (BP), differences in %ΔBV, and achievement of the target ultrafiltration volume as secondary outcomes were compared. IDH was defined as a reduction in systolic BP ≥20 mmHg from the baseline value at 10 min after HD initiation.ResultsNo significant differences were found in the prevalence of IDH, frequency of intervention for symptomatic IDH, and achievement of the target ultrafiltration volume between the groups. The %ΔBV was significantly fewer (-12.1 ± 4.8% vs. -14.4 ± 5.2%, p <0.001) in the HD with BV-UFC than that in the standard HD.ConclusionsHD with BV-UFC did not reduce the prevalence of IDH compared with standard HD. The relief of a relative BV reduction at the end of HD may be beneficial in patients undergoing HD with BV-UFC.Trial RegistrationUMIN, UMIN000024670. Registered on December 1, 2016.

Cardiovascular deconditioning during long-term spaceflight through multiscale modeling

Human spaceflight has been fascinating man for centuries, representing the intangible need to explore the unknown, challenge new frontiers, advance technology, and push scientific boundaries further. A key area of importance is cardiovascular deconditioning, that is, the collection of hemodynamic changes—from blood volume shift and reduction to altered cardiac function—induced by sustained presence in microgravity. A thorough grasp of the 0G adjustment point per se is important from a physiological viewpoint and fundamental for astronauts’ safety and physical capability on long spaceflights. However, hemodynamic details of cardiovascular deconditioning are incomplete, inconsistent, and poorly measured to date; thus a computational approach can be quite valuable. We present a validated 1D–0D multiscale model to study the cardiovascular response to long-term 0G spaceflight in comparison to the 1G supine reference condition. Cardiac work, oxygen consumption, and contractility indexes, as well as central mean and pulse pressures were reduced, augmenting the cardiac deconditioning scenario. Exercise tolerance of a spaceflight traveler was found to be comparable to an untrained person with a sedentary lifestyle. At the capillary–venous level significant waveform alterations were observed which can modify the regular perfusion and average nutrient supply at the cellular level. The present study suggests special attention should be paid to future long spaceflights which demand prompt physical capacity at the time of restoration of partial gravity (e.g., Moon/Mars landing). Since spaceflight deconditioning has features similar to accelerated aging understanding deconditioning mechanisms in microgravity are also relevant to the understanding of aging physiology on the Earth.

Identification of physiologic treatment targets with favourable haemodynamic consequences in heart failure with preserved ejection fraction.

AimsHeart failure with preserved ejection fraction (HFpEF) is characterized by complex pathophysiology including an impaired diastolic reserve. We recently showed that milrinone favourably modifies filling pressures at rest and during exertion in HFpEF patients; however, the responsible mechanism is uncertain. The objective of this study was to develop a clearer understanding of the acutely modifiable physiologic parameters that may be targeted in HFpEF.Methods and resultsWe conducted computer modelling simulations based on invasive haemodynamic assessments, by right heart catheterization, in HFpEF patients at baseline and in response to milrinone. Our aim was to develop a detailed understanding of the physiologic mechanisms, which accounted for the observed actions. The resultant circulatory model of HFpEF encompassed the left ventricular (LV) end‐systolic and end‐diastolic pressure–volume relations, together with stressed blood volume, heart rate, and arterial mechanics. To support the modelled action of milrinone, we conducted complementary LV conductance catheter and echocardiography studies in sheep to evaluate LV end‐systolic and end‐diastolic pressure–volume relations. In HFpEF patients, the acute haemodynamic effects of intravenous milrinone (n = 10) administration compared with placebo (n = 10) included significant reductions in right atrial pressure (7 ± 1 to 3 ± 1 mmHg, P < 0.001) and pulmonary capillary wedge pressure (13 ± 1 to 8 ± 1 mmHg, P < 0.001), while cardiac index increased (2.77 ± 0.19 to 3.15 ± 0.14 L/min/m2, P < 0.05), and mean arterial pressure remained unchanged (95 ± 2 to 93 ± 3 mmHg, P = not significant). Computer simulations showed that these haemodynamic effects were explained by a concomitant 31% reduction in stressed blood volume together with 44% increase in LV end‐systolic elastance (LV E es). Individually, changes in these parameters were not sufficient to explain the haemodynamic effects of milrinone. In vivo studies conducted in sheep (n = 5) showed that milrinone reduced LV filling pressure (8.0 ± 0.8 to 2.7 ± 0.6 mmHg, P < 0.01) and increased LV E es (0.96 ± 0.07 to 2.07 ± 0.49, P < 0.05), while no significant effect on LV stiffness was observed (0.038 ± 0.003 to 0.034 ± 0.008, P = not significant).ConclusionsThese data demonstrate that stressed blood volume in HFpEF represents a relevant physiologic target in HFpEF; however, concomitant modulation of other cardiovascular parameters including LV contractility may be required to achieve desirable haemodynamic effects.

Exercise heat acclimation has minimal effects on left ventricular volumes, function and systemic hemodynamics in euhydrated and dehydrated trained humans.

Heat acclimation (HA) may improve the regulation of cardiac output (Q̇) through increased blood volume (BV) and left ventricular (LV) diastolic filling and attenuate reductions in Q̇ during exercise-induced dehydration; however, these hypotheses have never been directly tested. Before and following 10-days exercise HA, eight males completed two trials of submaximal exercise in 33°C and 50% relative humidity while maintaining preexercise euhydrated body mass (EUH; -0.6 ± 0.4%) or becoming progressively dehydrated (DEH; -3.6 ± 0.7%). Rectal (Tre) and skin (Tsk) temperatures, heart rate (HR), LV volumes and function, systemic hemodynamics and BV were measured at rest and during bouts of semirecumbent cycling (55% V̇o2max) at 20, 100 and 180 min, interspersed by periods of upright exercise. Tre, BV, HR, LV volumes, LV systolic and diastolic function, and systemic hemodynamics were similar between trials at rest and during the first 20 min of exercise (all P > 0.05). These responses were largely unaffected by HA at 180 min in either hydration state. However, DEH induced higher Tre (0.6 ± 0.3°C) and HR (16 ± 7 beats/min) and lower end-diastolic volume (29 ± 16 mL), stroke volume (26 ± 16 mL), and Q̇ (2.1 ± 0.8 L/min) compared with EUH at 180 min (all P < 0.05), yet LV twist and untwisting rate were increased or maintained (P = 0.028 and 0.52, respectively). Findings indicate HA has minimal effects on LV volumes, LV mechanical function, and systemic hemodynamics during submaximal exercise in moderate heat, where HR and BV are similar. In contrast, DEH evokes greater hyperthermia and tachycardia, reduces BV, and impairs diastolic LV filling, lowering Q̇, regardless of HA state.NEW & NOTEWORTHY This study demonstrates that 10 days of exercise heat acclimation has minimal effects on left ventricular volumes, intrinsic cardiac function, and systemic hemodynamics during prolonged, repeated semirecumbent exercise in moderate heat, where heart rate and blood volume are similar to preacclimation levels. However, progressive dehydration is consistently associated with similar degrees of hyperthermia and tachycardia and reductions in blood volume, diastolic filling of the left ventricle, stroke volume, and cardiac output, regardless of acclimation state.

Cardiac and renal function interactions in heart failure with reduced ejection fraction: A mathematical modeling analysis.

Congestive heart failure is characterized by suppressed cardiac output and arterial filling pressure, leading to renal retention of salt and water, contributing to further volume overload. Mathematical modeling provides a means to investigate the integrated function and dysfunction of heart and kidney in heart failure. This study updates our previously reported integrated model of cardiac and renal functions to account for the fluid exchange between the blood and interstitium across the capillary membrane, allowing the simulation of edema. A state of heart failure with reduced ejection fraction (HF-rEF) was then produced by altering cardiac parameters reflecting cardiac injury and cardiovascular disease, including heart contractility, myocyte hypertrophy, arterial stiffness, and systemic resistance. After matching baseline characteristics of the SOLVD clinical study, parameters governing rates of cardiac remodeling were calibrated to describe the progression of cardiac hemodynamic variables observed over one year in the placebo arm of the SOLVD clinical study. The model was then validated by reproducing improvements in cardiac function in the enalapril arm of SOLVD. The model was then applied to prospectively predict the response to the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin, which has been shown to reduce heart failure events in HF-rEF patients in the recent DAPAHF clinical trial by incompletely understood mechanisms. The simulations predict that dapagliflozin slows cardiac remodeling by reducing preload on the heart, and relieves congestion by clearing interstitial fluid without excessively reducing blood volume. This provides a quantitative mechanistic explanation for the observed benefits of SGLT2i in HF-rEF. The model also provides a tool for further investigation of heart failure drug therapies.

Discarded plasma obtained after cord blood volume reduction as an alternative for fetal calf serum in mesenchymal stromal cells cultures.

Utilization of the fetal calf serum (FCS) carries a potential health risk and raises growing economic and ethical problems. Umbilical cord blood volume reduction, required for banking, provides clinical-grade umbilical cord blood plasma (UCBP) discarded as a waste. The aim of this study was to test whether serum derived from UCBP could replace FCS for the amplification of mesenchymal stromal cells (MSCs). To this end, the amplification of the MSCs and mesenchymal progenitors was estimated in the presence of serum derived from UCBP and its cytokine content was determined by cytometric bead array and enzyme-linked immunosorbent assay techniques. As a comparison, other sources of clinical-grade human serum were tested in parallel: serum derived from solvent/detergent-treated fresh-frozen plasma (S/D-FFP) and from platelet (PLT)-rich and PLT-poor umbilical plasma. Serum derived from UCBP-supplemented culture sustains identical amplification of MSCs and their progenitors as in the case of FCS addition. Furthermore, the assays reveal the presence in the serum derived from UCBP of cytokines influencing the properties of MSCs (basic fibroblast growth factor, transforming growth factor-β, vascular endothelial growth factor, and interleukin-8) or involved in the development of the myeloid lineage (thrombopoietin, erythropoietin, granulocyte-colony-stimulating factor, and granulocyte-macrophage-colony-stimulating factor). Also, our study indicates important differences between neonatal and adult-derived serum. Poor cytokine content in the S/D-FFP makes a less efficient replacement of FCS comparing to other human blood-derived supplements. Our work shows that the discarded human cord blood plasma from volume reduction is an easily obtainable and greatly available, xeno-free source of serum that is a highly efficient replacement of FCS in sustaining MSC growth.

Remodeling Matrix Synthesis in a Rat Model of Aortocaval Fistula and the Cyclic Stretch: Impaction in Pulmonary Arterial Hypertension-Congenital Heart Disease.

Pulmonary arterial hypertension-congenital heart disease (PAH-CHD) is characterized by systemic to pulmonary arterial shunts and sensitively responds to volume overload and stretch of the vascular wall leading to pulmonary vascular remodeling. We hypothesized that the responses of pulmonary artery smooth muscle cells (PASMCs) to mechanical stress-associated volume overload may promote vascular remodeling in PAH-CHD. Here, we show that significantly increased collagen was in the PA adventitial layer by trichrome staining in PAH-CHD patients and an aortocaval fistula (ACF) rat model in which chronic vascular volume overload induced-PAH. We assessed the gene expression profiles of SMC markers, extracellular matrix, and collagen in isolated SMCs from pulmonary and thoracic vessels with cyclic stretch-triggered responses by real-time PCR analysis. The data corresponded to collagen deposition, which modulated pulmonary vascular remodeling in clinical and experimental PAH-ACF cases as well as in cyclic stretch-triggered SMCs in an in vitro model. We observe that collagen I A2 (COLIA2) is expressed in the control rat, but collagen I A1 (COLIA1) and Notchs remarkably increase in the lungs of ACF rats. Interestingly, closing the left-to-right shunt that leads to a reduced blood volume in the PA system of ACF rats (ACFRs) decreased the expression of COLIA1 and increased that of collagen I A2(COLIA2). This study contributes to the stretch-induced responses of SMCs and provides important future directions for therapies aimed at preventing abnormal matrix protein synthesis in volume overload-induced pulmonary hypertension (PH).