Blood Volume Distribution Research Articles

Cardiovascular sex-differences: insights via physiology-based modeling and potential for noninvasive sensing via ballistocardiography.

In this study, anatomical and functional differences between men and women in their cardiovascular systems and how these differences manifest in blood circulation are theoretically and experimentally investigated. A validated mathematical model of the cardiovascular system is used as a virtual laboratory to simulate and compare multiple scenarios where parameters associated with sex differences are varied. Cardiovascular model parameters related with women's faster heart rate, stronger ventricular contractility, and smaller blood vessels are used as inputs to quantify the impact (i) on the distribution of blood volume through the cardiovascular system, (ii) on the cardiovascular indexes describing the coupling between ventricles and arteries, and (iii) on the ballistocardiogram (BCG) signal. The model-predicted outputs are found to be consistent with published clinical data. Model simulations suggest that the balance between the contractile function of the left ventricle and the load opposed by the arterial circulation attains similar levels in females and males, but is achieved through different combinations of factors. Additionally, we examine the potential of using the BCG waveform, which is directly related to cardiovascular volumes, as a noninvasive method for monitoring cardiovascular function. Our findings provide valuable insights into the underlying mechanisms of cardiovascular sex differences and may help facilitate the development of effective noninvasive cardiovascular monitoring methods for early diagnosis and prevention of cardiovascular disease in both women and men.

Impact of Blood Flow Restriction Exercise on Central Hemodynamics and Fluid Regulating Hormones.

The purpose of this study is to characterize both the efficacy of altered restriction pressures and consequences of optimized blood flow restriction (BFR) for altering the cardiovascular and fluid regulating response in humans. This work comprised a series of related trials. Phase 1: during semi-recumbent cycling (5 min, 60 W) with BFR at 0%, 50%, 75%, 100%, and 125% of participants' lowest arterial occlusion pressure (LOP) echocardiographic images were collected alongside continuous heart rate (HR) and blood pressure (BP). In phase 2, 24 h fluid balance (intake-output) and fluid-regulating hormone responses were measured after a practical BFR exercise session (treadmill walking: 5·3 min, 1 min rest, 5 km·h -1 , 5% incline, 100% LOP). Phase 3 examined the magnitude and effect of blood volume distribution following BFR treadmill walking using a modified CO-rebreathe technique. Cardiac ejection fraction remained stable irrespective of cuff pressure and despite a reduction in end-diastolic volume (Δ of 11 ± 9 mL, P = 0.02). HR and BP were highest at 100% LOP (ΔHR = 18 ± 19 bpm, ΔSBP = 51 ± 30 mm Hg, ΔDBP = 33 ± 15 mm Hg, ΔRate Pressure Product = 76 ± 32 bpm·mm Hg·100 -1 ). BFR treadmill walking stimulated a greater release of fluid-regulating hormones than normal walking (Δrenin = BFR: 25.3 ± 24.2 vs CON: 9.1 ± 11.8 ng·L -1 ; Δcopeptin = BFR: 50.1 ± 97.9 vs. CON: 0.43 ± 0.8 pmol·L -1 ), but no difference in fluid retention was observed ( P = 0.2). Approximately 27% of total blood volume was confined to the legs during BFR, but the relative volume trapped in the legs was not related to fluid-regulating hormone release (renin r = -0.04, P = 0.9; copeptin r = 0.27, P = 0.3). BFR exercise elicits the largest cardiovascular effect using 100% LOP, with evidence of appreciable fluid regulating hormonal response during a typical BFR exercise session. The relative volume of blood sequestered in the limb does not appear to drive this response.

Unraveling pathophysiologic mechanisms contributing to symptoms in patients with post-acute sequelae of COVID-19 (PASC): A retrospective study.

Patients with post-acute sequelae of COVID-19 (PASC) present with a decrease in physical fitness. The aim of this paper is to reveal the relations between the remaining symptoms, blood volume distribution, exercise tolerance, static and dynamic lung volumes, and overall functioning. Patients with PASC were retrospectively studied. Pulmonary function tests (PFT), 6-minute walk test (6MWT), and cardiopulmonary exercise test were performed. Chest CT was taken and quantified. Patients were divided into two groups: minor functional limitations (MFL) and severe functional limitations (SFL) based on the completed Post-COVID-19 Functional Status scale (PCFS). Twenty one patients (3 M; 18 FM), mean age 44 (IQR 21) were studied. Eighteen completed the PCFS (8 MFL; 10 SFL). VO2 max was suboptimal in both groups (not significant). 6MWT was significantly higher in MFL-group (p = 0.043). Subjects with SFL, had significant lower TLC (p = 0.029). The MFL-group had more air trapping (p = 0.036). Throughout the sample, air trapping correlated significantly with residual volume (RV) in L (p < 0.001). An increase in air trapping was related to an increase in BV5 (p < 0.001). Mean BV5 was 65% (IQR 5%). BV5% in patients with PASC was higher than in patients with acute COVID-19 infection. This increase in BV5% in patients with PASC is thought to be driven by the air trapping in the lobes. This study reveals that symptoms are more driven by occlusion of the small airways. Patients with more physical complaints have significantly lower TLC. All subjects encounter physical limitations as indicated by suboptimal VO2 max. Treatment should focus on opening or re-opening of small airways by recruiting alveoli.

Distribution of Aeration and Pulmonary Blood Volume in Healthy, ARDS and COVID-19 Lungs: A Dual-Energy Computed Tomography Retrospective Cohort Study

Few reports have studied lung aeration and perfusion in normal lungs, COVID-19, and ARDS from other causes (NC-ARDS) using dual-energy computed tomography pulmonary angiograms (DE-CTPA). To describe lung aeration and blood-volume distribution using DE-CTPAs of patients with NC-ARDS, COVID-19, and controls with a normal DE-CTPA ("healthy lungs"). We hypothesized that each of these conditions has unique ranges of aeration and pulmonary blood volumes. This retrospective, single-center study of DE-CTPAs included patients with COVID-19, NC-ARDS (Berlin criteria), and controls. Patients with macroscopic pulmonary embolisms were excluded. The outcomes studied were the (1) lung blood-volume in areas with different aeration levels (normal, ground glass opacities [GGO], consolidated lung) and (2) aeration/blood-volume ratios. Included were 20 patients with COVID-19 (10 milds, 10 moderate-severe), six with NC-ARDS, and 12 healthy-controls. Lung aeration was lowest in patients with severe COVID-19 24% (IQR13%-31%) followed by those with NC-ARDS 40%(IQR21%-46%). Blood-volume in GGO was lowest in patients with COVID-19 [moderate-severe:-28.6 (IQR-33.1-23.2); mild: -30.1 (IQR-33.3-23.4)] and highest in normally aerated areas in NC-ARDS -37.4 (IQR-52.5-30.2-) and moderate-severe COVID-19 -33.5(IQR-44.2-28.5). The median aeration/blood-volume ratio was lowest in severe COVID-19 but some values overlapped with those observed among patients with NC-ARDS. Severe COVID-19 disease is associated with low total aerated lung volume and blood-volume in areas with GGO and overall aeration/blood volume ratios, and with high blood volume in normal lung areas. In this hypothesis-generating study, these findings were most pronounced in severe COVID disease. Larger studies are needed to confirm these preliminary findings.

Chest dual-energy CT to assess the effects of steroids on lung function in severe COVID-19 patients

BackgroundSteroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung edema. Based on evidence from clinical trials, steroids are widely used in severe COVID-19. However, the effects of steroids on pulmonary gas volume and blood volume in this group of patients are unexplored.ObjectiveProfiting by dual-energy computed tomography (DECT), we investigated the relationship between the use of steroids in COVID-19 and distribution of blood volume as an index of impaired HPV. We also investigated whether the use of steroids influences lung weight, as index of lung edema, and how it affects gas distribution.MethodsSevere COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients’ cohort was divided into two groups depending on the administration of steroids. From each patient’s DECT, 20 gas volume maps and the corresponding 20 blood volume maps, evenly distributed along the cranial–caudal axis, were analyzed. As a proxy for HPV, pulmonary blood volume distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung edema, was estimated.ResultsSixty patients were analyzed, whereof 43 received steroids. Patients not exposed to steroids showed a more extensive non-perfused area (19% vs 13%, p < 0.01) and less homogeneous pulmonary blood volume of hypoinflated areas (kurtosis: 1.91 vs 2.69, p < 0.01), suggesting a preserved HPV compared to patients treated with steroids. Moreover, patients exposed to steroids showed a significantly lower lung weight (953 gr vs 1140 gr, p = 0.01). A reduction in alveolar–arterial difference of oxygen followed the treatment with steroids (322 ± 106 mmHg at admission vs 267 ± 99 mmHg at DECT, p = 0.04).ConclusionsThe use of steroids might cause impaired HPV and might reduce lung edema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, a reduced lung weight, as index of decreased lung edema, and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids.Trial registration: Clinical Trials ID: NCT04316884, Registered March 13, 2020.

Revisiting factors associated with blood culture positivity: Critical factors after the introduction of automated continuous monitoring blood culture systems.

Blood culture is the main tool used to identify causative pathogens. Adequate volume and number of culture sets are considered key to blood culture positivity rate. It is not known whether these factors remain critical to the positivity rate after the introduction of automated continuous blood culture system monitoring.We measured blood volume per bottle and described the distribution of blood volume and number of culture sets. Multivariate logistic regression was performed to determine the independent association of blood volume, number of culture sets, diagnosis of sepsis in a patient, and other covariates with blood culture results.Only 6.9% of the blood culture bottle volumes complied with the guidance (8–10 mL), with the highest culture positivity rate (18%). Of the culture events, only one set of blood was cultured in 60.9% of events. In the multivariate analysis, blood culture volume per event (odds ratio [OR], 1.09 [95% confidence interval [CI], 1.06–1.11]), patients with a diagnosis of sepsis (OR, 2.86 [95% CI, 2.06–3.98]), and samples from the emergency department (OR, 2.29 [95% CI, 1.72–3.04]), but not the number of culture sets (OR, 0.74 [95% CI, 0.50–1.12]), were observed to be statistically significant with respect to blood culture positivity rate.Our results revealed that the total blood culture volume and the diagnosis of sepsis were critical factors affecting blood culture positivity rate. However, the proportion of blood culture bottles with the optimal blood volume was very low, and optimizing blood volume would be key to increasing blood culture positivity rate.

Cardiovascular deconditioning increases GABA signaling in the nucleus tractus solitarii.

The nucleus tractus solitarii (nTS) is the major integrative brainstem region for autonomic modulation and processing of cardiovascular reflexes. GABA and glutamate are the main inhibitory and excitatory neurotransmitters, respectively, within this nucleus. Alterations in the GABA-glutamate regulation in the nTS are related to numerous cardiovascular comorbidities. Bedridden individuals and people exposed to microgravity exhibit dysautonomia and cardiovascular deconditioning that are mimicked in the hindlimb unloading (HU) rat model. We have previously shown in the nTS that HU increases glutamatergic neurotransmission yet decreases neuronal excitability. In this study, we investigated the effects of HU on nTS GABAergic neurotransmission. We hypothesized that HU potentiates GABA signaling via increased GABAergic release and postsynaptic GABA receptor expression. Following HU or control postural exposure, GABAergic neurotransmission was assessed using whole cell patch clamp whereas the magnitude of GABA release was evaluated via an intensity-based GABA sensing fluorescence reporter (iGABASnFR). In response to GABA interneuron stimulation, the evoked inhibitory postsynaptic current (nTS-IPSC) amplitude and area, as well as iGABASnFR fluorescence, were greater in HU than in control. HU also elevated the frequency but not the amplitude of spontaneous miniature IPSCs. Picoapplication of GABA produced similar postsynaptic current responses in nTS neurons of HU and control. Moreover, HU did not alter GABAA receptor α1 subunit expression, indicating minimal alterations in postsynaptic membrane receptor expression. These results indicate that HU increases GABAergic signaling in the nTS likely via augmented release of GABA from presynaptic terminals. Altogether, our data indicate GABA plasticity contributes to the autonomic and cardiovascular alterations following cardiovascular deconditioning (CVD).NEW & NOTEWORTHY Gravity influences distribution of blood volume and autonomic function. Microgravity and prolonged bed rest induce cardiovascular deconditioning (CVD). We used hindlimb unloading (HU), a rat analog for bed rest, to investigate CVD-induced neuroplasticity in the brainstem. Our data demonstrate that HU increases GABA modulation of nucleus tractus solitarii (nTS) neurons via presynaptic plasticity. Given the importance of nTS in integrating cardiovascular reflexes, this study provides new evidence on the central mechanisms behind CVD following HU.

A-55 | Peripheral Pulmonary Blood Volume Decreases in Patients with Intermediate Risk Acute Pulmonary Embolism Treated with Anticoagulation

Ultrasound-facilitated, catheter-directed fibrinolysis has been shown to increase peripheral pulmonary arterial blood volume distribution at 48 hours post-treatment as a mechanism for right ventricular (RV) recovery in intermediate risk pulmonary embolism (PE). The change in peripheral pulmonary blood volume distribution in patients receiving anticoagulation monotherapy remains unclear.

Gadoxetic Acid Uptake Rate as a Measure of Global and Regional Liver Function as Compared With Indocyanine Green Retention, Albumin-Bilirubin Score, and Portal Venous Perfusion

PurposeGlobal and regional liver function assessments are important for defining the magnitude and spatial distribution of dose to preserve functional liver parenchyma and reduce incidence of hepatotoxicity from radiation therapy for intrahepatic cancer treatment. This individualized liver function-guided radiation therapy strategy is critical for patients with heterogeneous and poor liver function, often observed in cirrhotic patients treated for hepatocellular carcinoma. This study aimed to validate k1 as a measure of global and regional function through comparison with 2 well-regarded global function measures: indocyanine green retention (ICGR) and albumin-bilirubin (ALBI). Methods and MaterialsSeventy-nine dynamic gadoxetic acid enhanced magnetic resonance imaging scans were acquired in 40 patients with hepatocellular carcinoma in institutional review board approved prospective protocols. Portal venous perfusion (kpv) was quantified from gadoxetic acid enhanced magnetic resonance imaging using a dual-input 2-compartment model, and gadoxetic acid uptake rate (k1) was fitted using a linearized single-input 2-compartment model chosen for robust k1 estimation. Four image-derived measures of global liver function were tested: (1) mean k1 multiplied by liver volume (k1VL) (functional volume), (2) mean k1 multiplied by blood distribution volume (k1Vdis), (3) mean kpv, and (4) liver volume (VL). The measure's correlation with corresponding ICGR and ALBI tests was assessed using linear regression. Voxel-wise similarity between k1 and kpv was compared using Spearman ranked correlation. ResultsSignificant correlations (P < .05) with ICGR and ALBI were found for k1VL, k1Vdis, and VL (in order of strength), but not for mean kpv. The mean ranked correlation coefficient between k1 and kpv maps was 0.09. k1 and kpv maps were predominantly mismatched in patients with poor liver function. ConclusionsThe metric combining function and liver volume (k1VL) was a stronger measure of global liver function compared with perfusion or liver volume alone, especially in patients with poor liver function. Gadoxetic acid uptake rate is promising for both global and regional liver function.

Imaging Pulmonary Blood Vessels and Ventilation-Perfusion Mismatch in COVID-19.

COVID-19 hypoxemic patients although sharing a same etiology (SARS-CoV-2 infection) present themselves quite differently from one another. Patients also respond differently to prescribed medicine and to prone Vs supine bed positions. A severe pulmonary ventilation-perfusion mismatch usually triggers moderate to severe COVID-19 cases. Imaging can aid the physician in assessing severity of COVID-19. Although useful for their portability X-ray and ultrasound serving on the frontline to evaluate lung parenchymal abnormalities are unable to provide information about pulmonary vasculature and blood flow redistribution which is a consequence of hypoxemia in COVID-19. Advanced imaging modalities such as computed tomography, single-photon emission tomography, and electrical impedance tomography use a sharp algorithm visualizing pulmonary ventilation-perfusion mismatch in the abnormal and in the apparently normal parenchyma. Imaging helps to access the severity of infection, lung performance, ventilation-perfusion mismatch, and informs strategies for medical treatment. This review summarizes the capacity of these imaging modalities to assess ventilation-perfusion mismatch in COVID-19. Despite having limitations, these modalities provide vital information on blood volume distribution, pulmonary embolism, pulmonary vasculature and are useful to assess severity of lung disease and effectiveness of treatment in COVID-19 patients.

Total Effective Vascular Compliance of a Global Mathematical Model for the Cardiovascular System

In this work, we determined the total effective vascular compliance of a global closed-loop model for the cardiovascular system by performing an infusion test of 500 mL of blood in four minutes. Our mathematical model includes a network of arteries and veins where blood flow is described by means of a one-dimensional nonlinear hyperbolic PDE system and zero-dimensional models for other cardiovascular compartments. Some mathematical modifications were introduced to better capture the physiology of the infusion test: (1) a physiological distribution of vascular compliance and total blood volume was implemented, (2) a nonlinear representation of venous resistances and compliances was introduced, and (3) main regulatory mechanisms triggered by the infusion test where incorporated into the model. By means of presented in silico experiment, we show that effective total vascular compliance is the result of the interaction between the assigned constant physical vascular compliance and the capacity of the cardiovascular system to adapt to new situations via regulatory mechanisms.

July 2021 at a glance: focus on blood volume distribution, haemodynamics and adherence to therapy.

July 2021 at a glance: focus on blood volume distribution, haemodynamics and adherence to therapy.

Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study

BackgroundCritically ill COVID-19 patients have pathophysiological lung features characterized by perfusion abnormalities. However, to date no study has evaluated whether the changes in the distribution of pulmonary gas and blood volume are associated with the severity of gas-exchange impairment and the type of respiratory support (non-invasive versus invasive) in patients with severe COVID-19 pneumonia.MethodsThis was a single-center, retrospective cohort study conducted in a tertiary care hospital in Northern Italy during the first pandemic wave. Pulmonary gas and blood distribution was assessed using a technique for quantitative analysis of dual-energy computed tomography. Lung aeration loss (reflected by percentage of normally aerated lung tissue) and the extent of gas:blood volume mismatch (percentage of non-aerated, perfused lung tissue—shunt; aerated, non-perfused dead space; and non-aerated/non-perfused regions) were evaluated in critically ill COVID-19 patients with different clinical severity as reflected by the need for non-invasive or invasive respiratory support.ResultsThirty-five patients admitted to the intensive care unit between February 29th and May 30th, 2020 were included. Patients requiring invasive versus non-invasive mechanical ventilation had both a lower percentage of normally aerated lung tissue (median [interquartile range] 33% [24–49%] vs. 63% [44–68%], p < 0.001); and a larger extent of gas:blood volume mismatch (43% [30–49%] vs. 25% [14–28%], p = 0.001), due to higher shunt (23% [15–32%] vs. 5% [2–16%], p = 0.001) and non-aerated/non perfused regions (5% [3–10%] vs. 1% [0–2%], p = 0.001). The PaO2/FiO2 ratio correlated positively with normally aerated tissue (ρ = 0.730, p < 0.001) and negatively with the extent of gas-blood volume mismatch (ρ = − 0.633, p < 0.001).ConclusionsIn critically ill patients with severe COVID-19 pneumonia, the need for invasive mechanical ventilation and oxygenation impairment were associated with loss of aeration and the extent of gas:blood volume mismatch.Graphic abstract

Obesity, venous capacitance, and venous compliance in heart failure with preserved ejection fraction.

Circulating blood volume is functionally divided between the unstressed volume, which fills the vascular space, and stressed blood volume (SBV), which generates vascular wall tension and intravascular pressure. With decreases in venous capacitance, blood functionally shifts to the SBV, increasing central venous pressure and pulmonary venous pressures. Obesity is associated with both elevated venous pressure and heart failure with preserved ejection fraction (HFpEF). To explore the mechanisms underlying this association, we evaluated relationships between blood volume distribution, venous compliance, and body mass in patients with and without HFpEF. Subjects with HFpEF (n= 62) and non-cardiac dyspnoea (NCD) (n= 79) underwent invasive haemodynamic exercise testing with echocardiography. SBV was estimated (eSBV) from measured haemodynamic variables fit to a comprehensive cardiovascular model. Compared to NCD, patients with HFpEF displayed a leftward-shifted central venous pressure-dimension relationship, indicating reduced venous compliance. eSBV was 81% higher at rest and 69% higher during exercise in HFpEF than NCD (both P< 0.0001), indicating reduced venous capacitance. Despite greater augmented eSBV with exercise, the increase in cardiac output was reduced in HFpEF, suggesting operation on the plateau of the Starling curve. Exercise eSBV was directly correlated with higher body mass index (r=0.77, P< 0.0001) and inversely correlated with right ventricular-pulmonary arterial coupling (r=-0.57, all P< 0.0001). Patients with HFpEF display reductions in systemic venous compliance and increased eSBV related to reduced venous capacitance, abnormalities in right ventricular-pulmonary artery interaction, and increased body fat. These data provide new evidence supporting an important role of venous dysfunction in obesity-related HFpEF and suggest that therapies that improve venous function may hold promise to improve clinical status in this cohort.

Altered pulmonary blood volume distribution as a biomarker for predicting outcomes in COVID-19 disease.

IntroductionEvidence suggests that vascular inflammation and thrombosis may be important drivers of poor clinical outcomes in patients with COVID-19. We hypothesised that a significant decrease in the percentage of blood volume in vessels with a cross-sectional area between 1.25 and 5 mm2 relative to the total pulmonary blood volume (BV5%) on chest computed tomography (CT) in COVID-19 patients is predictive of adverse clinical outcomes.MethodsWe performed a retrospective analysis of chest CT scans from 10 hospitals across two US states in 313 COVID-19-positive and 195 COVID-19-negative patients seeking acute medical care.ResultsBV5% was predictive of outcomes in COVID-19 patients in a multivariate model, with a BV5% threshold below 25% associated with OR 5.58 for mortality, OR 3.20 for intubation and OR 2.54 for the composite of mortality or intubation. A model using age and BV5% had an area under the receiver operating characteristic curve of 0.85 to predict the composite of mortality or intubation in COVID-19 patients. BV5% was not predictive of clinical outcomes in patients without COVID-19.ConclusionsThe data suggest BV5% as a novel biomarker for predicting adverse outcomes in patients with COVID-19 seeking acute medical care.

Assessment of Small Pulmonary Blood Vessels in COVID-19 Patients Using HRCT

Rationale and ObjectivesMounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on computed tomography (CT) are associated with histopathological markers of pulmonary vascular pruning, suggesting that quantitative CT analysis may eventually be useful in the assessment pulmonary vascular dysfunction more broadly.Materials and MethodsBuilding upon previous work, automated quantitative CT measures of small blood vessel volume and pulmonary vascular density were developed. Scans from 103 COVID-19 patients and 107 healthy volunteers were analyzed and their results compared, with comparisons made both on lobar and global levels.ResultsCompared to healthy volunteers, COVID-19 patients showed significant reduction in BV5 (pulmonary blood volume contained in blood vessels of <5 mm2) expressed as BV5/(total pulmonary blood volume; p < 0.0001), and significant increases in BV5-10 and BV 10 (pulmonary blood volumes contained in vessels between 5 and 10 mm2 and above 10 mm2, respectively, p < 0.0001). These changes were consistent across lobes.ConclusionCOVID-19 patients display striking anomalies in the distribution of blood volume within the pulmonary vascular tree, consistent with increased pulmonary vasculature resistance in the pulmonary vessels below the resolution of CT.

The Menopause Alters Aerobic Adaptations to High-Intensity Interval Training.

Postmenopausal women have lower resting cardiac function than premenopausal women, but whether the menopause influences maximal cardiac output and hence exercise capacity is unclear. It is possible that premenopausal and postmenopausal women achieve similar improvements in maximal aerobic capacity (V˙O2max) and cardiac output with exercise training via different regional left ventricular muscle function ("LV mechanics"), as suggested by in vitro and animal studies. The aim of this study was to investigate the effects of the menopause on LV mechanics and adaptations to exercise training. Twenty-five healthy untrained middle-age women (age, 45-58 yr; 11 premenopausal, 14 postmenopausal) completed 12 wk of exercise training. Before and after exercise training, (i) V˙O2max and blood volume were determined, and (ii) LV mechanics were assessed using echocardiography at rest and during two submaximal physiological tests - lower-body negative pressure and supine cycling. The increase in V˙O2max after exercise training was 9% smaller in postmenopausal than premenopausal women, concomitant with a smaller increase in blood volume (P < 0.05). However, cardiac output and LV volumes were not different between premenopausal and postmenopausal women (P > 0.05) despite altered regional LV muscle function, as indicated by higher basal mechanics in premenopausal women during the physiological tests after exercise training (P < 0.05). These findings are the first to confirm altered LV mechanics in postmenopausal women. In addition, the reduced aerobic adaptability to exercise training in postmenopausal women does not appear to be a central cardiac limitation and may be due to altered blood volume distribution and lower peripheral adaptations.

Mechanical Ventilation Redistributes Blood to Poorly Ventilated Areas in Experimental Lung Injury.

Determine the intra-tidal regional gas and blood volume distributions at different levels of atelectasis in experimental lung injury. Test the hypotheses that pulmonary aeration and blood volume matching is reduced during inspiration in the setting of minimal tidal recruitment/derecruitment and that this mismatching is an important determinant of hypoxemia. Preclinical study. Research laboratory. Seven anesthetized pigs 28.7 kg (SD, 2.1 kg). All animals received a saline-lavage surfactant depletion lung injury model. Positive end-expiratory pressure was varied between 0 and 20 cm H2O to induce different levels of atelectasis. Dynamic dual-energy CT images of a juxtadiaphragmatic slice were obtained, gas and blood volume fractions within three gravitational regions calculated and normalized to lung tissue mass (normalized gas volume and normalized blood volume, respectively). Ventilatory conditions were grouped based upon the fractional atelectatic mass in expiration (< 20%, 20-40%, and ≥ 40%). Tidal recruitment/derecruitment with fractional atelectatic mass in expiration greater than or equal to 40% was less than 7% of lung mass. In this group, inspiration-related increase in normalized gas volume was greater in the nondependent (818 µL/g [95% CI, 729-908 µL/g]) than the dependent region (149 µL/g [120-178 µL/g]). Normalized blood volume decreased in inspiration in the nondependent region (29 µL/g [12-46 µL/g]) and increased in the dependent region (39 µL/g [30-48 µL/g]). Inspiration-related changes in normalized gas volume and normalized blood volume were negatively correlated in fractional atelectatic mass in expiration greater than or equal to 40% and 20-40% groups (r = 0.56 and 0.40), but not in fractional atelectatic mass in expiration less than 20% group (r = 0.01). Both the increase in normalized blood volume in the dependent region and fractional atelectatic mass in expiration negatively correlated with PaO2/FIO2 ratio (ρ = -0.77 and -0.93, respectively). In experimental atelectasis with minimal tidal recruitment/derecruitment, mechanical inspiratory breaths redistributed blood volume away from well-ventilated areas, worsening PaO2/FIO2.

In vivo imaging of canine lung deformation: effects of posture, pneumonectomy, and inhaled erythropoietin.

Mechanical stresses on the lung impose the major stimuli for developmental and compensatory lung growth and remodeling. We used computed tomography (CT) to noninvasively characterize the factors influencing lobar mechanical deformation in relation to posture, pneumonectomy (PNX), and exogenous proangiogenic factor supplementation. Post-PNX adult canines received weekly inhalations of nebulized nanoparticles loaded with recombinant human erythropoietin (EPO) or control (empty nanoparticles) for 16 wk. Supine and prone CT were performed at two transpulmonary pressures pre- and post-PNX following treatment. Lobar air and tissue volumes, fractional tissue volume (FTV), specific compliance (Cs), mechanical strains, and shear distortion were quantified. From supine to prone, lobar volume and Cs increased while strain and shear magnitudes generally decreased. From pre- to post-PNX, air volume increased less and FTV and Cs increased more in the left caudal (LCa) than in other lobes. FTV increased most in the dependent subpleural regions, and the portion of LCa lobe that expanded laterally wrapping around the mediastinum. Supine deformation was nonuniform pre- and post-PNX; strains and shear were most pronounced in LCa lobe and declined when prone. Despite nonuniform regional expansion and deformation, post-PNX lobar mechanics were well preserved compared with pre-PNX because of robust lung growth and remodeling establishing a new mechanical equilibrium. EPO treatment eliminated posture-dependent changes in FTV, accentuated the post-PNX increase in FTV, and reduced FTV heterogeneity without altering absolute air or tissue volumes, consistent with improved microvascular blood volume distribution and modestly enhanced post-PNX alveolar microvascular reserves.NEW & NOTEWORTHY Mechanical stresses on the lung impose the major stimuli for lung growth. We used computed tomography to image deformation of the lung in relation to posture, loss of lung units, and inhalational delivery of the growth promoter erythropoietin. Following loss of one lung in adult large animals, the remaining lung expanded and grew while retaining near-normal mechanical properties. Inhalation of erythropoietin promoted more uniform distribution of blood volume within the remaining lung.

Effects of CO2 on Regional Cerebral Blood Flow Regulation During Lower‐Body Negative Pressure

Cerebrovascular CO2 reactivity (CVR) is differentially regulated between anterior and posterior cerebral circulations, where the cerebrovasculature is responsive to increases (dilation) or decreases (constriction) in arterial CO2. In addition, anterior and posterior cerebral blood flow (CBF) may be differentially regulated during lower body negative pressure (LNBP), where blood volume distribution is experimentally moved toward the lower extremities, imposing an acute hypovolemic and hypotensive challenge. However, the effects of steady‐state increases and decreases in CO2 on the CBF response to LBNP‐imposed hypotension has not been investigated systematically. The aim of this study was to investigate regional CBF responses to incremental (i.e., ramp) LBNP in steady‐state hypo‐ and hypercapnia in anterior and posterior cerebral circulations. We hypothesized that posterior CBF would be better maintained during LBNP at all levels of CO2 and that regional patterns of CBF regulation during LBNP would be unchanged by steady‐state CO2 perturbations. In 14 healthy participants, we measured cardiovascular and cerebrovascular variables, including heart rate (HR; ECG), mean arterial pressure (MAP; finometry), and using transcranial Doppler ultrasound, cerebral blood velocity (CBV) and cerebrovascular conductance (CVC; CBV/MAP) in the middle (MCA) and posterior cerebral artery (PCA). We carried out three separate incremental LBNP protocols (−20, −40, −60 and −80 mm Hg; 3‐min each) at three randomized steady‐state levels of CO2: (a) hypocapnia (−8 mm Hg; i.e., coached hyperventilation), (b) normocapnia (i.e., room air), and (c) hypercapnia (+8 mm Hg; 5% inspired CO2). We found that HR increased incrementally with LBNP in all CO2 conditions (P&lt;0.001). At −80mmHg LBNP, MAP decreased in hypo‐ (P=0.046) and normocapnia (P=0.002). MCA CBV decreased in normo‐ (P&lt;0.001) and hypercapnia (P&lt;0.001). PCA CBV also decreased in normo‐ (P=0.011) and hypercapnia (P=0.002). However, MCA CVC decreased in normo‐ (P=0.01) and hypercapnia (P&lt;0.001), whereas PCA CVC did not decrease during LBNP at all levels of CO2. These findings demonstrate greater sensitivity in anterior cerebral circulation compared to posterior during a moderate LBNP challenge with alterations in CO2. Our data elucidate a comprehensive understanding of regional CVR during LBNP‐induced hypovolemia, and may be applied to understanding preferential protection of posterior brain structures during hypovolemic shock.Support or Funding InformationNSERC Discovery and MRU Faculty of Science and TechnologyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.