Prognostic implications of volume status assessed by blood volume analysis in ambulatory heart failure.

The prognostic implications of intravascular volume status assessed by blood volume analysis (BVA) in ambulatory heart failure (HF) remain uncertain. The incremental benefits of assessing volume status, beyond the well-established filling pressures, in predicting HF outcomes are unknown.

Study of the f-cell ratio using plasma dilution and albumin mass kinetics.

BACKGROUND: The f-cell ratio of 0.91 is a conversion factor between the hematocrit measured in peripheral blood and the hematocrit obtained by separate measurements of the red blood cell mass and plasma volume. The physiological background of the f-cell ratio is unclear. METHODS: Data were retrieved from 155 intravenous infusion experiments where 15-25 mL/kg of crystalloid fluid diluted the blood hemoglobin and plasma albumin concentrations. The hemodilution was converted to plasma dilution using the peripheral hematocrit, and the volume of distribution of exogenous albumin was calculated in 41 volunteers who received 20 % or 5 % albumin by intravenous infusion. Finally, the kinetics of plasma albumin was studied during 98 infusion experiments with 20 % albumin. RESULTS: Plasma dilution based on hemoglobin and albumin showed a median difference of -0.001 and a mean difference of 0.000 (N = 2184), which demonstrates that these biomarkers indicate the same expandable vascular space. In contrast, exogenous albumin occupied a volume that was 10 % larger than the plasma volume indicated by the anthropometric equations of Nadler et al. and Retzlaff et al. The kinetic analysis identified a secondary compartment that was 450 mL in size and rapidly exchanged albumin with the circulating plasma. CONCLUSIONS: The results suggest that the f-cell ratio is due to rapid exchange of albumin between the plasma and a non-expandable compartment located outside the circulating blood (possibly the liver sinusoids). This means that the hematocrit measured in peripheral blood correctly represents the ratio between the red cell volume and the circulating plasma volume.

Sprint interval training in the postpartum period maintains the enhanced cardiac output of pregnancy: A case study.

During pregnancy an increased cardiac output ( Q ̇ $\dot{Q}$ ) and blood volume (BV) occur to support fetal growth. Increased Q ̇ $\dot{Q}$ and BV also occur during chronic endurance exercise training and benefit performance. We investigated if sprint interval training (SIT) undertaken early postpartum maintains the elevated Q ̇ $\dot{Q}$ and BV of pregnancy and benefits performance. The participant, a competitive field hockey player and former cyclist, visited our laboratory at 2 weeks of gestation (baseline) and postpartum pre-, mid- and post-intervention (PPpre, PPmid and PPpost). Delivery was uncomplicated and she felt ready to start the SIT programme 5 weeks postpartum. Inert gas rebreathing was used to measure peak exercise Q ̇ $\dot{Q}$ ( Q ̇ $\dot{Q}$ peak); V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ was measured with a metabolic cart; and postpartum haematological values were measured with carbon monoxide rebreathing. The 18 SIT sessions progressed from four to eight sprints at 130% of V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ peak power output. Q ̇ $\dot{Q}$ peak increased from baseline at all postpartum time points (baseline 16.2 vs. 17.5, 16.8 and 17.2 L/min at PPpre, PPmid and PPpost, respectively). Relative V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ remained below baseline values at all postpartum measurements (baseline 44.9 vs. 41.0, 42.3 and 42.5 mL/kg/min at PPpre, PPmid and PPpost, respectively) whereas absolute V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ rapidly reached baseline values postpartum (baseline 3.19 vs. 3.12, 3.23 and 3.18 L/min at PPpre, PPmid and PPpost, respectively). Postpartum BV (5257, 4271 and 5214 mL at PPpre, PPmid and PPpost, respectively) and Hbmass (654, 525 and 641 g at PPpre, PPmid and PPpost, respectively) were similar between PPpre and PPpost but decreased alongside Q ̇ $\dot{Q}$ peak at PPmid. Peak power was returned to pre-pregnancy values by intervention end (302 vs. 303 W, baseline vs. PPpost). These findings show that SIT undertaken early postpartum defends the elevated Q ̇ $\dot{Q}$ peak of pregnancy and rapidly returns absolute V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ and peak power to baseline levels.

Comparison of intradialytic continuous and interval training on hemodynamics and dialysis adequacy: A crossover randomized controlled trial.

AIM: Circulating blood volume (BV) during exercise changes depending on the intensity and duration, and post-exercise hypotension is observed after continuous exercise. We investigated the safety and efficacy of both interval and continuous IDE at anaerobic threshold (AT) levels with respect to hemodynamic stability and dialysis efficiency. METHODS: In this crossover randomized controlled trial, 16 patients on haemodialysis were subjected to three trial arms, including non-IDE, interval-IDE, and continuous-IDE arms. Systolic blood pressure (SBP), BV, and ultraviolet absorbance - an indicator of dialysis efficiency - were continuously measured, and each change was compared between the three arms by two-way analysis of variance. RESULTS: Continuous IDE decreased SBP from post-exercise to the end of dialysis compared with baseline (pre 142.8 ± 19.0 vs. post 127.5 ± 24.5 mmHg, p = .02), whereas interval IDE maintained better SBP levels post-exercise (pre 139.9 ± 17.1 vs. post 140.1 ± 15.8 mmHg, p = 1.0) than continuous IDE (non-IDE 133.2 ± 19.9 vs. interval 140.1 ± 15.8 vs. continuous 127.5 ± 24.5 mmHg, p = .04). Moreover, interval IDE caused less tiredness and few symptoms (p < .05), despite reaching higher intensity than continuous IDE (p = .001). The BV of each IDE arm decreased during exercise and recovered post-exercise to the same level as non-IDE. Ultraviolet absorbance was not different between each arm (p = .16). CONCLUSION: AT-level interval IDE maintains better hemodynamic stability from post-exercise to the end of dialysis and may represent a novel approach that can be effectively performed with fewer symptoms.

Differences in circulating blood volume changes during emergence from general anesthesia in transcatheter aortic valve implantation and MitraClip implantation.

PURPOSE: We aimed to compare changes in the circulating blood volume (CBV) during emergence from general anesthesia in patients undergoing transcatheter aortic valve implantation (TAVI) and MitraClip implantation. METHOD: We included 97 patients who underwent TAVI or MitraClip implantation. The primary outcome was the rate of change in the estimated CBV associated with emergence from general anesthesia. The secondary outcomes were hemoglobin and hematocrit values before and after emergence from anesthesia for each procedure. Additionally, the independent factors associated with changes in the estimated CBV were assessed using multiple regression analysis. RESULTS: In the TAVI group, the hemoglobin concentration increased from 9.6 g/dL before emergence from anesthesia to 10.8 g/dL after emergence (P < 0.001; mean difference, 1.2 g/dL, 95% confidence interval [CI] 1.1-1.3 g/dL). Conversely, no statistically significant change was observed in the hemoglobin concentration before and after emergence from anesthesia in the MitraClip group. The mean rate of change in the estimated CBV was - 15.4% (standard deviation [SD] 6.4%) in the TAVI group and - 2.4% (SD, 4.7%) in the MitraClip group, indicating a significant decrease in the estimated CBV in the former than in the latter (P < 0.001; mean difference, 13.0%; 95% CI 9.9-16.1%). CONCLUSION: Emergence from general anesthesia increased the hemoglobin concentration and decreased the estimated CBV in patients undergoing TAVI but did not elicit significant changes in patients undergoing MitraClip implantation. These results may provide a rationale for minimizing blood transfusions during general anesthesia in patients undergoing these procedures.

Layer-fMRI VASO with short stimuli and event-related designs at 7 T.

Layers and columns are the dominant processing units in the human (neo)cortex at the mesoscopic scale. While the blood oxygenation dependent (BOLD) signal has a high detection sensitivity, it is biased towards unwanted signals from large draining veins at the cortical surface. The additional fMRI contrast of vascular space occupancy (VASO) has the potential to augment the neuroscientific interpretability of layer-fMRI results by means of capturing complementary information of locally specific changes in cerebral blood volume (CBV). Specifically, VASO is not subject to unwanted sensitivity amplifications of large draining veins. Because of constrained sampling efficiency, it has been mainly applied in combination with efficient block task designs and long trial durations. However, to study cognitive processes in neuroscientific contexts, or probe vascular reactivity, short stimulation periods are often necessary. Here, we developed a VASO acquisition procedure with a short acquisition period and sub-millimeter resolution. During visual event-related stimulation, we show reliable responses in visual cortices within a reasonable number of trials (∼20). Furthermore, the short TR and high spatial specificity of our VASO implementation enabled us to show differences in laminar reactivity and onset times. Finally, we explore the generalizability to a different stimulus modality (somatosensation). With this, we showed that CBV-sensitive VASO provides the means to capture layer-specific haemodynamic responses with high spatio-temporal resolution and is able to be used with event-related paradigms.

Serial blood volume measurements in patients with compensated chronic heart failure: How do volume profiles change over time?

Among patients with chronic heart failure (HF) intravascular volume profiles vary significantly despite similar clinical compensation. However, little is known regarding changes in blood volume (BV) profiles over time. The objective of this analysis was to identify the extent and character of changes in volume profiles over time. A prospective analysis was undertaken in patients who were hospitalized and treated for fluid overload. Quantitative BV analyses were obtained in a compensated state at hospital discharge (baseline) and follow-up at 1, 3, and 6 mo. Data were available on 10 patients who remained stable without rehospitalization or medication change over a 6-mo period. Baseline BV profiles were highly variable at hospital discharge with an average deviation of +28% above normal in 6 patients and normal BV in 4 patients. Over the follow-up period, the median change in BV was -201 mL [-3% (-6, +3%)] from baseline with profiles remaining in the same volume category in 9 out of 10 patients. Crossover from normal BV to mild contraction (-13% of normal) occurred in one patient. Red blood cell mass demonstrated the largest change over 6 mo [median -275 (-410, +175) mL] with a deviation from normal of -14 (-20, +8) % (reflecting mild anemia). These findings suggest that BV profiles in clinically compensated patients with HF do not change substantially over a 6-mo period regardless of baseline expanded or normal BV. This lack of change in volume profiles particularly from an expanded BV has implications for long-term volume management, clinical outcomes, and also our understanding of volume homeostasis in HF.NEW & NOTEWORTHY The novel findings of this study demonstrate that blood volume profiles while highly variable in clinically compensated patients with HF on stable medical therapy do not change substantially over a 6-mo period regardless of baseline expanded or normal blood volumes. This lack of change in volume profiles particularly from an expanded blood volume has implications for long-term volume management and also for how we understand the pathophysiology of volume homeostasis in chronic HF.

Selective elevation in external carotid artery flow during acute gravitational transition to microgravity during parabolic flight.

This study sought to determine to what extent acute exposure to microgravity (0 G) and related increases in central blood volume (CBV) during parabolic flight influence the regional redistribution of intra and extra cranial cerebral blood flow (CBF). Eleven healthy participants performed during two parabolic flights campaigns aboard the Airbus A310-ZERO G aircraft. The response of select variables for each of the 15 parabolas involving exposure to both 0 G and hypergravity (1.8 G) were assessed in the seated position. Mean arterial blood pressure (MAP) and heart rate (HR) were continuously monitored and used to calculate stroke volume (SV), cardiac output ([Formula: see text]), and systemic vascular resistance (SVR). Changes in CBV were measured using an impedance monitor. Extracranial flow through the internal carotid, external carotid, and vertebral artery ([Formula: see text]ICA, [Formula: see text]ECA, and [Formula: see text]VA), and intracranial blood velocity was measured by duplex ultrasound. When compared with 1-G baseline condition, 0 G increased CBV (+375 ± 98 mL, P = 0.004) and [Formula: see text] (+16 ± 14%, P = 0.024) and decreased SVR (-7.3 ± 5 mmHg·min·L-1, P = 0.002) and MAP (-13 ± 4 mmHg, P = 0.001). [Formula: see text]ECA increased by 43 ± 46% in 0 G (P = 0.030), whereas no change was observed for CBF, [Formula: see text]ICA, or [Formula: see text]VA (P = 0.102, P = 0.637, and P = 0.095, respectively).NEW & NOTEWORTHY Our findings demonstrate that in microgravity there is a selective increase in external carotid artery blood flow whereas global and regional cerebral blood flow remained preserved. To what extent this reflects an adaptive, neuroprotective response to counter overperfusion remains to be established.

The increase in cardiac output induced by a decrease in positive end-expiratory pressure reliably detects volume responsiveness: the PEEP-test study.

BACKGROUND: In patients on mechanical ventilation, positive end-expiratory pressure (PEEP) can decrease cardiac output through a decrease in cardiac preload and/or an increase in right ventricular afterload. Increase in central blood volume by fluid administration or passive leg raising (PLR) may reverse these phenomena through an increase in cardiac preload and/or a reopening of closed lung microvessels. We hypothesized that a transient decrease in PEEP (PEEP-test) may be used as a test to detect volume responsiveness. METHODS: Mechanically ventilated patients with PEEP ≥ 10 cmH2O ("high level") and without spontaneous breathing were prospectively included. Volume responsiveness was assessed by a positive PLR-test, defined as an increase in pulse-contour-derived cardiac index (CI) during PLR ≥ 10%. The PEEP-test consisted in reducing PEEP from the high level to 5 cmH2O for one minute. Pulse-contour-derived CI (PiCCO2) was monitored during PLR and the PEEP-test. RESULTS: We enrolled 64 patients among whom 31 were volume responsive. The median increase in CI during PLR was 14% (11-16%). The median PEEP at baseline was 12 (10-15) cmH2O and the PEEP-test resulted in a median decrease in PEEP of 7 (5-10) cmH2O, without difference between volume responsive and unresponsive patients. Among volume responsive patients, the PEEP-test induced a significant increase in CI of 16% (12-20%) (from 2.4 ± 0.7 to 2.9 ± 0.9 L/min/m2, p < 0.0001) in comparison with volume unresponsive patients. In volume unresponsive patients, PLR and the PEEP-test increased CI by 2% (1-5%) and 6% (3-8%), respectively. Volume responsiveness was predicted by an increase in CI > 8.6% during the PEEP-test with a sensitivity of 96.8% (95% confidence interval (95%CI): 83.3-99.9%) and a specificity of 84.9% (95%CI 68.1-94.9%). The area under the receiver operating characteristic curve of the PEEP-test for detecting volume responsiveness was 0.94 (95%CI 0.85-0.98) (p < 0.0001 vs. 0.5). Spearman's correlation coefficient between the changes in CI induced by PLR and the PEEP-test was 0.76 (95%CI 0.63-0.85, p < 0.0001). CONCLUSIONS: A CI increase > 8.6% during a PEEP-test, which consists in reducing PEEP to 5 cmH2O, reliably detects volume responsiveness in mechanically ventilated patients with a PEEP ≥ 10 cmH2O. Trial registration ClinicalTrial.gov (NCT 04,023,786). Registered July 18, 2019. Ethics Committee approval CPP Est III (N° 2018-A01599-46).

Improved Selectivity in 7 T Digit Mapping Using VASO-CBV.

Functional magnetic resonance imaging (fMRI) at Ultra-high field (UHF, ≥ 7 T) benefits from significant gains in the BOLD contrast-to-noise ratio (CNR) and temporal signal-to-noise ratio (tSNR) compared to conventional field strengths (3 T). Although these improvements enabled researchers to study the human brain to unprecedented spatial resolution, the blood pooling effect reduces the spatial specificity of the widely-used gradient-echo BOLD acquisitions. In this context, vascular space occupancy (VASO-CBV) imaging may be advantageous since it is proposed to have a higher spatial specificity than BOLD. We hypothesized that the assumed higher specificity of VASO-CBV imaging would translate to reduced overlap in fine-scale digit representation maps compared to BOLD-based digit maps. We used sub-millimeter resolution VASO fMRI at 7 T to map VASO-CBV and BOLD responses simultaneously in the motor and somatosensory cortices during individual finger movement tasks. We assessed the cortical overlap in different ways, first by calculating similarity coefficient metrics (DICE and Jaccard) and second by calculating selectivity measures. In addition, we demonstrate a consistent topographical organization of the targeted digit representations (thumb-index-little finger) in the motor areas. We show that the VASO-CBV responses yielded less overlap between the digit clusters than BOLD, and other selectivity measures were higher for VASO-CBV too. In summary, these results were consistent across metrics and participants, confirming the higher spatial specificity of VASO-CBV compared to BOLD.

Grey-box modeling and hypothesis testing of functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal high-definition tDCS in healthy humans.

Transcranial direct current stimulation (tDCS) has been shown to evoke hemodynamics response; however, the mechanisms have not been investigated systematically using systems biology approaches. Our study presents a grey-box linear model that was developed from a physiologically detailed multi-compartmental neurovascular unit model consisting of the vascular smooth muscle, perivascular space, synaptic space, and astrocyte glial cell. Then, model linearization was performed on the physiologically detailed nonlinear model to find appropriate complexity (Akaike information criterion) to fit functional near-infrared spectroscopy (fNIRS) based measure of blood volume changes, called cerebrovascular reactivity (CVR), to high-definition (HD) tDCS. The grey-box linear model was applied on the fNIRS-based CVR during the first 150 seconds of anodal HD-tDCS in eleven healthy humans. The grey-box linear models for each of the four nested pathways starting from tDCS scalp current density that perturbed synaptic potassium released from active neurons for Pathway 1, astrocytic transmembrane current for Pathway 2, perivascular potassium concentration for Pathway 3, and voltage-gated ion channel current on the smooth muscle cell for Pathway 4 were fitted to the total hemoglobin concentration (tHb) changes from optodes in the vicinity of 4x1 HD-tDCS electrodes as well as on the contralateral sensorimotor cortex. We found that the tDCS perturbation Pathway 3 presented the least mean square error (MSE, median <2.5%) and the lowest Akaike information criterion (AIC, median -1.726) from the individual grey-box linear model fitting at the targeted-region. Then, minimal realization transfer function with reduced-order approximations of the grey-box model pathways was fitted to the ensemble average tHb time series. Again, Pathway 3 with nine poles and two zeros (all free parameters), provided the best Goodness of Fit of 0.0078 for Chi-Square difference test of nested pathways. Therefore, our study provided a systems biology approach to investigate the initial transient hemodynamic response to tDCS based on fNIRS tHb data. Future studies need to investigate the steady-state responses, including steady-state oscillations found to be driven by calcium dynamics, where transcranial alternating current stimulation may provide frequency-dependent physiological entrainment for system identification. We postulate that such a mechanistic understanding from system identification of the hemodynamics response to transcranial electrical stimulation can facilitate adequate delivery of the current density to the neurovascular tissue under simultaneous portable imaging in various cerebrovascular diseases.

Improvement of predicted hematocrit values after the initiation of cardiopulmonary bypass in cardiovascular surgery.

Hematocrit (Hct) values after the initiation of cardiopulmonary bypass (CPB) must be maintained appropriately to avoid perioperative complications. Therefore, an accurate prediction is required. However, the standard prediction equation often results in actual values that are lower than the predicted values. This study aimed to clarify the limits of agreement (LOA) and bias of the prediction equations and investigate better the prediction equations. A retrospective study was performed on adult patients between April 2015 and December 2020. Study 1 included 158 patients, and Study 2 included 55 patients. The primary outcomes were the LOA and bias between the predicted and measured Hct values after the initiation of CPB, and two studies were conducted. In Study 1, total blood volume (TBV) was estimated, and the new blood volume index (BVI) was calculated. BVI was also evaluated for the overall value and gender differences. Therefore, the patient's background was compared by gender differences. In, Study 2 the conventional predicted equation (Eq. 1), the predicted equation using the new BVI (Eq. 2), and the predicted equation using the new BVI including physiological factors in the TBV equation (Eq. 3) were compared. In Study 1, BVI was 53 (44-67) mL/kg. In Study 2, bias ± LOA was - 2.5 ± 6.8% for Eq. 1, 0.1 ± 6.6% for Eq. 2, and 0.4 ± 6.2% for Eq. 3. The new equation is expected to predict the Hct value after the initiation of CPB with better LOA and bias than the conventional equation.

The overlooked significance of plasma volume for successful adaptation to high altitude in Sherpa and Andean natives.

In contrast to Andean natives, high-altitude Tibetans present with a lower hemoglobin concentration that correlates with reproductive success and exercise capacity. Decades of physiological and genomic research have assumed that the lower hemoglobin concentration in Himalayan natives results from a blunted erythropoietic response to hypoxia (i.e., no increase in total hemoglobin mass). In contrast, herein we test the hypothesis that the lower hemoglobin concentration is the result of greater plasma volume, rather than an absence of increased hemoglobin production. We assessed hemoglobin mass, plasma volume and blood volume in lowlanders at sea level, lowlanders acclimatized to high altitude, Himalayan Sherpa, and Andean Quechua, and explored the functional relevance of volumetric hematological measures to exercise capacity. Hemoglobin mass was highest in Andeans, but also was elevated in Sherpa compared with lowlanders. Sherpa demonstrated a larger plasma volume than Andeans, resulting in a comparable total blood volume at a lower hemoglobin concentration. Hemoglobin mass was positively related to exercise capacity in lowlanders at sea level and in Sherpa at high altitude, but not in Andean natives. Collectively, our findings demonstrate a unique adaptation in Sherpa that reorientates attention away from hemoglobin concentration and toward a paradigm where hemoglobin mass and plasma volume may represent phenotypes with adaptive significance at high altitude.

Baseline Values of the Compensatory Reserve Index in a Healthy Pediatric Population.

The objective of this study is to describe the compensatory reserve index (CRI) baseline values in a healthy cohort of healthy pediatric patients and evaluate the existing correlation with other physiological parameters that influence compensatory hemodynamic mechanisms. CRI is a computational algorithm that has been broadly applied to non-invasively estimate hemodynamic vascular adaptations during acute blood loss. So far, there is a lack of baseline values from healthy individuals, which complicates accurately estimating the severity of the hemodynamic compromise. Additionally, the application of this technology in pediatric populations is limited to a few reports, highlighting a marked variability by age, weight, and other physiological parameters. The CRI of 205 healthy subjects from 0 to 60 years of age were prospectively evaluated from January to February 2020 at several public outpatient clinics in El Salvador; vital signs and sociodemographic data were also collected during this period. After data collection, baseline values were classified for each age group. Multiple correlation models were tested between the CRI and the other physiological parameters. CRI value varies significantly for each age group, finding for patients under 18 years old a mean value lower than 0.6, which is currently considered the lower normal limit for adults. CRI presents strong correlations with other physiological variables such as age, weight, estimated blood volume, and heart rate (R > 0.8, R2 > 0.6, p < 0.0001). There is significant variability in the CRI normal values observed in healthy patients based on age, weight, estimated blood volume, and heart rate.

Classification of Blood Volume Decompensation State via Machine Learning Analysis of Multi-Modal Wearable-Compatible Physiological Signals.

This paper presents a novel computational algorithm to estimate blood volume decompensation state based on machine learning (ML) analysis of multi-modal wearable-compatible physiological signals. To the best of our knowledge, our algorithm may be the first of its kind which can not only discriminate normovolemia from hypovolemia but also classify hypovolemia into absolute hypovolemia and relative hypovolemia. We realized our blood volume classification algorithm by (i) extracting a multitude of features from multi-modal physiological signals including the electrocardiogram (ECG), the seismocardiogram (SCG), the ballistocardiogram (BCG), and the photoplethysmogram (PPG), (ii) constructing two ML classifiers using the features, one to classify normovolemia vs. hypovolemia and the other to classify hypovolemia into absolute hypovolemia and relative hypovolemia, and (iii) sequentially integrating the two to enable multi-class classification (normovolemia, absolute hypovolemia, and relative hypovolemia). We developed the blood volume decompensation state classification algorithm using the experimental data collected from six animals undergoing normovolemia, relative hypovolemia, and absolute hypovolemia challenges. Leave-one-subject-out analysis showed that our classification algorithm achieved an F1 score and accuracy of (i) 0.93 and 0.89 in classifying normovolemia vs. hypovolemia, (ii) 0.88 and 0.89 in classifying hypovolemia into absolute hypovolemia and relative hypovolemia, and (iii) 0.77 and 0.81 in classifying the overall blood volume decompensation state. The analysis of the features embedded in the ML classifiers indicated that many features are physiologically plausible, and that multi-modal SCG-BCG fusion may play an important role in achieving good blood volume classification efficacy. Our work may complement existing computational algorithms to estimate blood volume compensatory reserve as a potential decision-support tool to provide guidance on context-sensitive hypovolemia therapeutic strategy.

AI-Enabled Advanced Development for Assessing Low Circulating Blood Volume for Emergency Medical Care: Comparison of Compensatory Reserve Machine-Learning Algorithms.

The application of artificial intelligence (AI) has provided new capabilities to develop advanced medical monitoring sensors for detection of clinical conditions of low circulating blood volume such as hemorrhage. The purpose of this study was to compare for the first time the discriminative ability of two machine learning (ML) algorithms based on real-time feature analysis of arterial waveforms obtained from a non-invasive continuous blood pressure system (Finometer®) signal to predict the onset of decompensated shock: the compensatory reserve index (CRI) and the compensatory reserve metric (CRM). One hundred ninety-one healthy volunteers underwent progressive simulated hemorrhage using lower body negative pressure (LBNP). The least squares means and standard deviations for each measure were assessed by LBNP level and stratified by tolerance status (high vs. low tolerance to central hypovolemia). Generalized Linear Mixed Models were used to perform repeated measures logistic regression analysis by regressing the onset of decompensated shock on CRI and CRM. Sensitivity and specificity were assessed by calculation of receiver-operating characteristic (ROC) area under the curve (AUC) for CRI and CRM. Values for CRI and CRM were not distinguishable across levels of LBNP independent of LBNP tolerance classification, with CRM ROC AUC (0.9268) being statistically similar (p = 0.134) to CRI ROC AUC (0.9164). Both CRI and CRM ML algorithms displayed discriminative ability to predict decompensated shock to include individual subjects with varying levels of tolerance to central hypovolemia. Arterial waveform feature analysis provides a highly sensitive and specific monitoring approach for the detection of ongoing hemorrhage, particularly for those patients at greatest risk for early onset of decompensated shock and requirement for implementation of life-saving interventions.

Algebraic formulas characterizing an alternative to Guyton's graphical analysis relevant for heart failure.

Although Guyton's graphical analysis of cardiac output-venous return has become a ubiquitous tool for explaining how circulatory equilibrium emerges from heart-vascular interactions, this classical model relies on a formula for venous return that contains unphysiological assumptions. Furthermore, Guyton's graphical analysis does not predict pulmonary venous pressure, which is a critical variable for evaluating heart failure patients' risk of pulmonary edema. Therefore, the purpose of the present work was to use a minimal closed-loop mathematical model to develop an alternative to Guyton's analysis. Limitations inherent in Guyton's model were addressed by 1) partitioning the cardiovascular system differently to isolate left ventricular function and lump all blood volumes together, 2) linearizing end-diastolic pressure-volume relationships to obtain algebraic solutions, and 3) treating arterial pressures as constants. This approach yielded three advances. First, variables related to morbidities associated with left ventricular failure were predicted. Second, an algebraic formula predicting left ventricular function was derived in terms of ventricular properties. Third, an algebraic formula predicting flow through the portion of the system isolated from the left ventricle was derived in terms of mechanical properties without neglecting redistribution of blood between systemic and pulmonary circulations. Although complexities were neglected, approximations necessary to obtain algebraic formulas resulted in minimal error, and predicted variables were consistent with reported values.

Global REACH 2018: Andean highlanders, chronic mountain sickness and the integrative regulation of resting blood pressure.

NEW FINDINGS: What is the central question of this study? Does chronic mountain sickness (CMS) alter sympathetic neural control and arterial baroreflex regulation of blood pressure in Andean (Quechua) highlanders? What is the main finding and its importance? Compared to healthy Andean highlanders, basal sympathetic vasomotor outflow is lower, baroreflex control of muscle sympathetic nerve activity is similar, supine heart rate is lower and cardiovagal baroreflex gain is greater in mild CMS. Taken together, these findings reflect flexibility in integrative regulation of blood pressure that may be important when blood viscosity and blood volume are elevated in CMS. ABSTRACT: The high-altitude maladaptation syndrome chronic mountain sickness (CMS) is characterized by excessive erythrocytosis and frequently accompanied by accentuated arterial hypoxaemia. Whether altered autonomic cardiovascular regulation is apparent in CMS is unclear. Therefore, during the 2018 Global REACH expedition to Cerro de Pasco, Peru (4383 m), we assessed integrative control of blood pressure (BP) and determined basal sympathetic vasomotor outflow and arterial baroreflex function in eight Andean natives with CMS ([Hb] 22.6 ± 0.9 g·dL-1 ) and seven healthy highlanders ([Hb] 19.3 ± 0.8 g·dL-1 ). R-R interval (RRI, electrocardiogram), beat-by-beat BP (photoplethysmography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest and during pharmacologically induced changes in BP (modified Oxford test). Although [Hb] and blood viscosity (7.8 ± 0.7 vs. 6.6 ± 0.7 cP; d = 1.7, P = 0.01) were elevated in CMS compared to healthy highlanders, cardiac output, total peripheral resistance and mean BP were similar between groups. The vascular sympathetic baroreflex MSNA set-point (i.e. MSNA burst incidence) and reflex gain (i.e. responsiveness) were also similar between groups (MSNA set-point, d = 0.75, P = 0.16; gain, d = 0.2, P = 0.69). In contrast, in CMS the cardiovagal baroreflex operated around a longer RRI (960 ± 159 vs. 817 ± 50 ms; d = 1.4, P = 0.04) with a greater reflex gain (17.2 ± 6.8 vs. 8.8 ± 2.6 ms·mmHg-1 ; d = 1.8, P = 0.01) versus healthy highlanders. Basal sympathetic vasomotor activity was also lower compared to healthy highlanders (33 ± 11 vs. 45 ± 13 bursts·min-1 ; d = 1.0, P = 0.08). In conclusion, our findings indicate adaptive differences in basal sympathetic vasomotor activity and heart rate compensate for the haemodynamic consequences of excessive erythrocyte volume and contribute to integrative blood pressure regulation in Andean highlanders with mild CMS.

Changes in prefrontal cerebral oxygenation and microvascular blood volume in hypoxia and possible association with acute mountain sickness.

NEW FINDINGS: What is the central question of this study? The role of the cerebral haemodynamic response to either normobaric or hypobaric hypoxia in people susceptible to acute mountain sickness (AMS) is still under debate. Prefrontal cortex near-infrared spectroscopy-derived parameters were monitored in normobaric hypoxia at rest and during moderate-intensity exercise in AMS-prone and non-AMS individuals. What is the main finding and its importance? The AMS-prone individuals did not increase microvascular blood volume and showed lower prefrontal cerebral oxygenation in normobaric hypoxia both at rest and during exercise compared with non-AMS subjects, suggesting that these changes might underpin later development of AMS at altitude. ABSTRACT: The aim of this study was to evaluate changes in prefrontal cerebral oxygenation and microvascular blood volume during exercise in normobaric hypoxia and to investigate possible associations with the occurrence of acute mountain sickness (AMS) at altitude. Twenty-two healthy individuals (age, 26 ± 4 years; peak oxygen uptake, 42 ± 4 ml kg-1  min-1 ) were tested in two different conditions: normoxia (NORM) and normobaric hypoxia (fraction of inspired O2  = 0.13; HYPO). Data were collected at rest and during submaximal constant-speed exercise. The peripheral oxyhaemoglobin saturation was measured by finger pulse oximeter. Changes in prefrontal cerebral oxygenation (ΔHbO2 ), deoxygenation (ΔHHb) and microvascular blood volume (ΔHbtot ) were obtained by near-infrared spectroscopy. Within 2 weeks after laboratory testing, subjects rapidly ascended to 3647 m a.s.l., and AMS was evaluated using the Lake Louise scale. Eight subjects were AMS+ , whereas 14 were AMS- . During NORM, near-infrared spectroscopy variables did not change from baseline values both at rest and during exercise, with similar results in AMS+ and AMS- subjects. During HYPO, ΔHHb increased to a similar extent in both groups, both at rest and during exercise. The ΔHbO2 was significantly less in AMS+ compared with AMS- subjects, both at rest [-3.23 ± 5.90 versus 1.44 ± 2.14 µm, P = 0.04, effect size (ES) = 1.1, respectively] and during exercise (-6.56 ± 5.51 versus 0.37 ± 4.36 µm, P < 0.01, ES = 1.2, respectively). Total haemoglobin did not change from baseline, both at rest (-1.67 ± 9.53 µm) and during exercise (-0.96 ± 9.12 µm) in AMS+ subjects, which was significantly different from the AMS- group (5.49 ± 3.99 µm, P = 0.03, ES = 1.0 and 8.17 ± 7.34 µm, P = 0.02, ES = 1.0, respectively). Individuals prone to AMS seem to be unable to increase microvascular blood volume and to maintain oxygenation at the cerebral level during exercise in acute normobaric hypoxia, suggesting that these changes might underpin later development of AMS.

Decreased Muscular Perfusion in Dermatomyositis: Initial Results Detected by Inflow-Based Vascular-Space-Occupancy MRI.

OBJECTIVE. This study aimed to determine whether inflow-based vascular-space-occupancy (iVASO) MRI could reproducibly quantify skeletal muscle perfusion and differentiate patients with dermatomyositis (DM) from healthy subjects. MATERIALS AND METHODS. A total of 25 patients with DM and 22 healthy volunteers underwent iVASO MRI in a 3-T MRI scanner. Maximum and mean arteriolar muscle blood volume (MBV) values of four subgroups of muscles (normal muscles, morphologically normal-appearing muscles, edematous muscles, and atrophic or fat-infiltrated muscles) were obtained. Maximum and mean arteriolar MBV values were compared among the different subgroups, and repeat testing was performed in 20 subjects to assess reproducibility. RESULTS. Compared with normal muscles in healthy subjects, morphologically normal-appearing muscles, edematous muscles, and atrophic or fat-infiltrated muscles in patients with DM showed a significant decrease of both maximum and mean arteriolar MBV (p < .001). Both parameters were significantly lower in atrophic or fat-infiltrated muscles than in morphologically normal-appearing and edematous muscles (p < .001). ROC AUCs for discriminating patients with DM from healthy volunteers were 0.842 and 0.812 for maximum and mean arteriolar MBV values, respectively. As a measure of test-retest studies, the intraclass correlation coefficients (ICCs) were 0.990 (95% CI, 0.986-0.993) and 0.990 (95% CI, 0.987-0.993) for maximum and mean arteriolar MBV, respectively. For interobserver reproducibility, the ICCs were 0.989 (95% CI, 0.986-0.991) and 0.980 (95% CI, 0.975-0.983), respectively. CONCLUSION. iVASO MRI can reproducibly quantify arteriolar MBV in the thigh and discriminate between healthy volunteers and patients with DM.