Changes In Total Blood Volume Research Articles

Sodium loading in ambulatory patients with heart failure with reduced ejection fraction: Mechanistic insights into sodium handling.

Sodium restriction was not associated with improved outcomes in heart failure patients in recent trials. The skin might act as a sodium buffer, potentially explaining tolerance to fluctuations in sodium intake without volume overload, but this is insufficiently understood. Therefore, we studied the handling of an increased sodium load in patients with heart failure with reduced ejection fraction (HFrEF). Twenty-one ambulatory, stable HFrEF patients and 10 healthy controls underwent a 2-week run-in phase, followed by a 4-week period of daily 1.2 g (51 mmol) sodium intake increment. Clinical, echocardiographic, 24-h urine collection, and bioelectrical impedance data were collected every 2 weeks. Blood volume, skin sodium content, and skin glycosaminoglycan content were assessed before and after sodium loading. Sodium loading did not significantly affect weight, blood pressure, congestion score, N-terminal pro-brain natriuretic peptide, echocardiographic indices of congestion, or total body water in HFrEF (all p > 0.09). There was no change in total blood volume (4748 ml vs. 4885 ml; p = 0.327). Natriuresis increased from 150 mmol/24 h to 173 mmol/24 h (p = 0.024), while plasma renin decreased from 286 to 88 μU/L (p = 0.002). There were no significant changes in skin sodium content, total glycosaminoglycan content, or sulfated glycosaminoglycan content (all p > 0.265). Healthy controls had no change in volume status, but a higher increase in natriuresis without any change in renin. Selected HFrEF patients can tolerate sodium loading, with increased renal sodium excretion and decreased neurohormonal activation.

Baroreflex control model for cardiovascular system subjected to postural changes under normal and orthostatic conditions

Baroreflex dysfunction is one of the common causes associated with the cardiovascular system. The buffering capability and baroreflex gain influences large variation in blood pressure for short term control. For regulating the blood pressure, an integrated analytical model for baroreflex control along with the cardiovascular system is presented to study the complex interactions between autonomic nervous system and cardiovascular system. In the proposed model, the autonomic nervous system utilizes sympathetic and parasympathetic nerve activities. This comprises a heart modeled by Mulier’s approach, systemic vasculature, baroreceptor sensor using stress-strain based Voigt model and Hodgkin-Huxley based autonomic nervous control. This model can handle the distribution of total blood volume changes under the influence of gravity upon postural changes by means of short term baroreflex control. The simulation is carried out for the integrated model along with (i) non pulsatile and (ii) pulsatile model of heart. The proposed model is validated for supine to standing position under influence of gravity. To show the efficiency of the proposed model, the simulation is carried out further for (i) postural changes like supine to standing and standing to supine under normal condition and (ii) Orthostatic hypotension and hypertension conditions. Also the robustness of the proposed pulsatile model is tested by introducing disturbance signal in mean arterial pressure under various postural changes.

Long Duration Bed Rest Modifies Cardiovagal Baroreflex Control but not Baroreflex Control of Muscle Sympathetic Action Potential Activity in Humans

Our understanding of altered neuro-cardiovascular control following long-duration inactivity via head-down bed rest (HDBR) is incomplete. Here, we retrospectively analyzed two long-duration HDBR studies, including female (n=17; 32±5 years) and male (n=16; 29±7 years) cohorts, to determine whether HDBR 1) alters spontaneous cardiovagal baroreflex sensitivity (cBRS) similarly between males and females and 2) alters spontaneous baroreflex control of muscle sympathetic action potentials (AP) in males. Heart rate (HR; electrocardiogram) and arterial blood pressure (BP; finger-plethysmography) were continuously measured during 5-minutes of supine rest prior to and following 60-days bed rest in a -6° head-down position. Spontaneous cBRS was assessed by the relationship between R-R interval and systolic BP analyzed using the linear regression sequence method. Recordings of multi-unit muscle sympathetic nerve activity (peroneal microneurography) were obtained and a continuous wavelet transform detected APs which were grouped into AP clusters with similar morphology (n=10, all males). Baroreflex threshold for AP cluster discharge was assessed by linear regression analysis of the relationship between AP cluster discharge probability and diastolic BP. No change in resting HR (64±9 versus 66±9 /min, P=0.12) or mean BP (91.2±9.0 versus 90.6±9.2 mmHg, P=0.73) occurred after HDBR. Reductions in cBRS after HDBR (-4.1±9.4 ms/mmHg, Time effect: P<0.01) were similar between males and females (Time-by-Sex effect: P=0.51) and not related to changes in total blood volume (r2=0.045, P=0.24). Grouped AP clusters demonstrated heterogenous arterial baroreflex threshold gain according to AP cluster morphology (Cluster effect: P<0.01) which was unaltered following HDBR (Time-by-Cluster effect: P=0.43). In summary, males and females similarly attenuate cBRS following 60-days of HDBR and novel evidence indicates HDBR does not alter spontaneous baroreflex control of muscle sympathetic APs in males.

Not all fluid overloads are the same: some practical considerations for better decongestion

Not all fluid overloads are the same: some practical considerations for better decongestion

Cerebral Perfusion Monitoring Using Near-Infrared Spectroscopy During Head-Up Tilt Table Test in Patients With Orthostatic Intolerance.

The head-up tilt table test (HUT) is one of the primary clinical examinations for evaluating orthostatic intolerance (OI). HUT can be divided into three phases: dynamic tilt phase (supine to tilt up), static tilt phase (remain tilted at 70°), and post tilt phase (tilt down back to supine position). Commonly, blood pressure (BP) and heart rate (HR) are monitored to observe for OI symptoms, but are indirect measurements of cerebral perfusion and can lead to inaccurate HUT evaluation. In this study, we implemented a 108-channel near-infrared spectroscopy (NIRS) probe to characterize HUT performance by monitoring cerebral hemodynamic changes for healthy controls (HCs), OI patients with normal HUT results, and OI patients with positive HUT results: vasovagal syncope (VS), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), and orthostatic hypertension (OHT). By the end of the static tilt phase, OI patients typically did not show a complete recovery back to baseline cerebral oxygenation and total blood volume compared to HCs. We characterized the return to cerebral homeostasis by polynomial fitting total blood volume changes and determining the inflection point. The OI patients with normal HUT results, VS, OH, or OHT showed a delay in the return to cerebral homeostasis compared to the HC group during HUT.

Assessing hyperthermia-induced vasodilation in human skin in vivo using optoacoustic mesoscopy.

The aim of this study was to explore the unique imaging abilities of optoacoustic mesoscopy to visualize skin structures and microvasculature with the view of establishing a robust approach for monitoring heat-induced hyperemia in human skin in vivo. Using raster-scan optoacoustic mesoscopy (RSOM), we investigated whether optoacoustic (photoacoustic) mesoscopy can identify changes in skin response to local heating at microvasculature resolution in a cross-sectional fashion through skin in the human forearm. We visualized the heat-induced hyperemia for the first time with single-vessel resolution throughout the whole skin depth. We quantified changes in total blood volume in the skin and their correlation with local heating. In response to local heating, total blood volume increased 1.83- and 1.76-fold, respectively, in the volar and dorsal aspects of forearm skin. We demonstrate RSOM imaging of the dilation of individual vessels in the skin microvasculature, consistent with hyperemic response to heating at the skin surface. Our results demonstrate great potential of RSOM for elucidating the morphology, functional state and reactivity of dermal microvasculature, with implications for diagnostics and disease monitoring. Image: Cross-sectional view of skin microvasculature dilated in response to hyperthermia.

Effect Of Chronic Xenon Supplementation On Hematological Parameters, Cardiorespiratory Fitness, and Athletic Performance

ObjectiveXenon is an inhalational anesthetic with the potential to improve athletic performance and cardiorespiratory fitness via proposed increases in total blood volume. This study aimed to determine the effect of a four‐week xenon supplementation protocol on total blood volume, maximal oxygen uptake (V̇2max) and 3‐kilometre time trial performance in trained individuals.MethodsFourteen subjects (32 ± 12 years; 71% male) were assessed for total blood volume through the carbon monoxide rebreathing method, cardiorespiratory fitness via V̇O2max on a treadmill test, and athletic performance using a 3 km time trial. Following baseline assessments, subjects were matched for sex, age and V̇O2max, and were randomised to 12 sessions of gas inhalation over four weeks (2 minutes of inhalation on 3 days per week); 1) xenon, n = 7 (70% xenon, 21% oxygen, 9% nitrogen) or 2) sham gas, n=7 (7% carbon dioxide, 21% oxygen, 62% nitrogen) dosing. Subjects were blinded to group allocation and all outcomes were re‐assessed following the four‐week dosing period. Within‐group mean differences and 95% confidence intervals for outcomes of interest are presented in Table 1. Differences between the xenon and sham gas group over time were tested using two‐way repeated measures ANOVA and are represented by P values.ResultsXenon and sham groups were equal at baseline for all outcomes of interest (Table 1). Twelve subjects completed the four‐week dosing intervention and are included in the analyses; one subject withdrew after a single xenon dose due to nausea and one subject was withdrawn after one week of xenon inhalation due to adverse symptoms during and after dosing which resembled sleep paralysis. Blinding was equally effective between groups; subjects in the xenon group were 65% certain of group allocation, while subjects in the sham group were 63% certain of group allocation. There were no significant differences between xenon or sham gas groups for changes in total blood volume, V̇O2max, or 3 km time trial performance (Table 1).ConclusionsFour weeks of xenon inhalation did not result in significant changes in total blood volume, cardiorespiratory fitness or athletic performance in comparison to a sham gas. Given the presence of adverse symptoms in approximately 30% (2 out of 7) subjects and a clear absence of physiological and performance benefits, our findings do not support the use of xenon as a performance enhancing substance.Support or Funding InformationThis study was supported in part by funding from the Partnership for Clean Competition Research Collaborative.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

THU0424 Near-infrared spectroscopy during exercise and recovery in children with juvenile dermatomyositis

BackgroundChildren with Juvenile Dermatomyositis (JDM) suffer from diminished exercise tolerance1-5, a clinical condition that may be linked to microvascular disturbances in the muscle tissue6. Near-infrared spectroscopy (NIRS) may represent a...

Respiratory effects of changing the volume load imposed on the peripheral venous system

This study was designed to determine if acute distension of the hindlimb venous circulation stimulates breathing, thereby contributing to the respiratory responses to rapid changes in total blood volume. In 10 spontaneously breathing anesthetized sheep, we withdrew 15 ml kg(-1) of blood from a femoral vein over approximately 1-2 min. We then compared the respiratory effects of infusing this venous blood back into the femoral veins across two conditions: the inferior vena cava (IVC) was either unobstructed or obstructed by a balloon-tipped catheter. We found that when blood was withdrawn and blood volume decreased, an absolute increase in breathing often occurred, but more importantly that a relative hyperventilation was always observed. When this blood was re-infused into the animal, effectively increasing blood volume, the respiratory response depended upon whether or not the IVC was open or obstructed. With the IVC unobstructed, a relative hypoventilation occurred, accompanied by an increase in alveolar PCO(2). In contrast, when the venous blood was re-infused and the IVC was obstructed, ventilation increased significantly, and the response was often hypocapnic. These results indicate that increasing the volume load in the venous circulation increases breathing, and that the transduction mechanism is contained within the peripheral venous system. Further, the respiratory drive from this sensory mechanism is subject to modulation via changes in the circulatory status, most likely within the arterial side.

Effect of postural changes on lower limb blood volume, detected with non-invasive photoplethysmography

This paper describes the effect of passive leg raising on blood volume change in the lower limb, using a dual probe photoplethysmography (PPG) system employing a tissue optics model. The normalized AC/DC ratio and DC value are introduced from the model to evaluate the dynamic pulsation and total blood volume changes due to postural effects. The AC and DC components of PPG signals were collected from a passive leg raising protocol. With the leg raised, the normalized AC/DC ratio significantly decreased when supine, while the normalized DC value increased significantly in both supine and reclining positions. The parameters from the stationary leg showed similar but smaller responses. These results demonstrate a local and systemic physiological phenomenon in the lower limb blood volume change caused by postural changes. The normalized AC/DC ratio and DC value derived from the tissue optics model could be applied to assess the blood volume change.

Relative Blood Volume Changes Underestimate Total Blood Volume Changes during Hemodialysis

Measurements of relative blood volume changes (DeltaRBV) during hemodialysis (HD) are based on hemoconcentration and assume uniform mixing of erythrocytes and plasma throughout the circulation. However, whole-body hematocrit (Ht) is lower than systemic Ht. During HD, a change in the ratio between whole-body to systemic Ht (F cell ratio) is likely to occur as a result of a net shift of low Ht blood from the microcirculation to the macrocirculation. Hence, DeltaRBV may differ significantly from total blood volume changes (DeltaTBV). Therefore, this study compared DeltaRBV and DeltaTBV during HD. Plasma and erythrocyte volumes were measured using (125)I- and (123)I-radioiodinated albumin and (51)Cr-labeled erythrocytes, respectively. After validation of the standardized method in two patients on a nondialysis day, seven patients completed the protocol during HD. (125)I-albumin and (51)Cr-labeled erythrocytes were administered 20 min before the start of HD. (123)I-albumin was administered at 160 min into the HD session to quantify and correct for (125)I-albumin leakage. DeltaRBV was measured continuously throughout HD. The F cell ratio was derived from whole-body and systemic Ht. Total ultrafiltration volume was 2450 +/- 770 ml. TBV declined from 5905 +/- 824 to 4877 +/- 722 ml during HD. Thus, TBV declined 17.3 +/- 4.4%, whereas the RBV decline was only 8.2 +/- 3.7% (P = 0.001). The F cell ratio increased from 0.896 +/- 0.036 to 0.993 +/- 0.049 during HD (P = 0.002). DeltaRBV significantly underestimates DeltaTBV during HD. The rise in F cell ratio strongly suggests that during HD, blood translocates from the microcirculation to the macrocirculation, probably as a cardiovascular compensatory mechanism in response to hypovolemia.

Functional MR Imaging during Hypercapnia and Hyperoxia: Noninvasive Tool for Monitoring Changes in Liver Perfusion and Hemodynamics in a Rat Model1

To prospectively assess functional magnetic resonance (MR) imaging during hypercapnia and hyperoxia for monitoring changes in liver perfusion and hemodynamics in rats. All experiments were performed with approval of an animal care and use committee. Functional T2*-weighted gradient-echo MR images of the rat liver were acquired during hyperoxia and graded hypercapnia (n=24). Additional images were acquired during portal vein ligation (n=4), induced hypovolemia (n=5), and 70% hepatectomy (n=5). Hypercapnic effects were confirmed with Doppler ultrasonography and with gadopentetate dimeglumine. Differences between groups were analyzed by using Wilcoxon rank sum test, except for the graded hypercapnia, for which one-way analysis of variance was used. Liver signal intensity (SI) increased due to hyperoxia; the percentage change in SI was seven times greater than that in muscle tissue; this reflects higher vascularity of the liver. Liver SI decreased due to hypercapnia; the percentage change in SI was negative in the liver but positive in the muscle (P<.001). Induced hypovolemia resulted in considerable decreases in functional MR imaging response; this reflects lower liver perfusion. Clinical applicability of the functional MR imaging method was proved by monitoring changes in liver perfusion that resulted from liver resection. In the liver, the magnitude of the percentage change in SI induced by hypercapnia and hyperoxia reflects changes in total blood volume; whereas percentage change in SI values induced by hypercapnia from a negative to a positive value reflects relative changes in portal-to-arterial blood flow ratio.

Arterial versus Total Blood Volume Changes during Neural Activity-Induced Cerebral Blood Flow Change: Implication for BOLD fMRI

Quantifying both arterial cerebral blood volume (CBV(a)) changes and total cerebral blood volume (CBV(t)) changes during neural activation can provide critical information about vascular control mechanisms, and help to identify the origins of neurovascular responses in conventional blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI). Cerebral blood flow (CBF), CBV(a), and CBV(t) were quantified by MRI at 9.4 T in isoflurane-anesthetized rats during 15-s duration forepaw stimulation. Cerebral blood flow and CBV(a) were simultaneously determined by modulation of tissue and vessel signals using arterial spin labeling, while CBV(t) was measured with a susceptibility-based contrast agent. Baseline versus stimulation values in a region centered over the somatosensory cortex were: CBF=150+/-18 versus 182+/-20 mL/100 g/min, CBV(a)=0.83+/-0.21 versus 1.17+/-0.30 mL/100 g, CBV(t)=3.10+/-0.55 versus 3.41+/-0.61 mL/100 g, and CBV(a)/CBV(t)=0.27+/-0.05 versus 0.34+/-0.06 (n=7, mean+/-s.d.). Neural activity-induced absolute changes in CBV(a) and CBV(t) are statistically equivalent and independent of the spatial extent of regional analysis. Under our conditions, increased CBV(t) during neural activation originates mainly from arterial rather than venous blood volume changes, and therefore a critical implication is that venous blood volume changes may be negligible in BOLD fMRI.

Investigating the BOLD effect during infusion of Gd-DTPA using rapid T2* mapping.

This work aimed to investigate the effects of administering Gd-DTPA on the BOLD effect, and to determine the feasibility of using this approach to measure fractional changes in blood volume and blood oxygenation on neuronal activation during a visual paradigm. A linear relationship between cortical R(2)(*) and the intravascular concentration of Gd-DTPA was demonstrated. The change in R(2)(*) in the visual cortex on activation at 3 T (in the absence of Gd-DTPA) was found to be 1.38 +/- 0.31 s(-1) (N = 4). The fractional change in total blood volume during visual activation was calculated to be 28% +/- 7% (N = 4). The absolute increase in venous blood oxygenation on activation (DeltaY) was estimated to be 21% +/- 4% (N = 4) (assuming HCT = 0.4, resting blood oxygenation = 60%, fraction of volume change that was venous = 36%, and the resting venous fraction of the blood volume = 70%). Simulations showed that the estimated change in venous blood oxygenation was sensitive to the assumed venous blood fraction, and that the estimated fractional change in blood oxygenation was insensitive to whether the change in blood volume occurred in the arterial or venous network.

Effect of Postural Change on Blood Volume in Long-Term Hemodialysis Patients

In healthy subjects, the blood volume (BV) increases rapidly after postural change from standing to the supine position. However, little is known about the effect of postural change on BV in long-term hemodialysis (HD) patients. Therefore, we have examined the BV change caused by adopting the supine position from standing by continuous hematocrit monitoring, using the CRIT-LINE instrument, in 8 anuric HD patients. The hematocrit was monitored for 25 min with the patient in the supine position just before HD. The percentage change in the BV (% Δ BV) was calculated from the hematocrit and approximated using the equation: % Δ BV = b – [1 – exp(–c × time (min)] –a × time (min). Coefficient a was the slope of the linear part in the % Δ BV, b was the magnitude of BV increase and c was the rate of BV increase. Then we examined the relationship between the coefficients (a, b and c) and clinical parameters. In all patients, % Δ BV increased quickly after adopting the supine position. The mean increases were 2.8 ± 0.6% after 5 min and 4.8 ± 0.5% after 25 min. There was a significant correlation between the value of % Δ BV calculated from the hematocrit and the value calculated using above equation (0.92 < r < 0.99, p < 0.001). Although coefficient a did not correlate with a clinical parameter, coefficient b showed a significant positive linear correlation with the serum albumin level (r = 0.816, p < 0.05) and coefficient c showed a significant positive linear correlation with the percentage change in interdialytic weight gain (r = 0.736, p < 0.05). Furthermore, based on the % Δ BV, we calculated the change in total BV, which had increased by 181.5 ± 21.9 ml after 25 min in the supine position. In conclusion, the change in the BV with time by continuous hematocrit monitoring using the CRIT-LINE instrument can be approximated by a modified monoexponential equation. BV increased quickly in HD patients after postural change from standing to the supine position.

Evaluation of Anemia in Angiotensin Converting Enzyme (ACE) Knockout Mice.

P2 Using targeted homologous recombination, we made two lines of mice that lack ACE. ACE.1 mice are null for all ACE activity while ACE.2 mice lack tissue ACE but retain 1/3 normal plasma ACE activity. Both strains have a marked decrease in blood pressure and are unable to produce a concentrated urine. ACE.1 mice have renal failure, as measured by a reduced creatinine clearance and an elevated serum creatinine, when compared to wild type mice; ACE.2 mice have no evidence of renal failure as indicated by a normal serum creatinine and creatine clearance. Surprisingly, both ACE.1 and ACE.2 mice are anemic with a reduction in hematocrit (38.5 +/- 1.3% and 38.3 +/- 0.8% respectively vs 48.4 +/- 0.9% for wild type) and serum hemoglobin (12.0 +/- 0.3 mg/dl and 11.7 +/- 0.2 mg/dl vs 14.7 +/- 0.3 mg/dl for wild type). In both strains, serum erythropoietin is elevated. Neither strain differs from wild type in regard to MCV, MCH, or MCHC, nor does either strain show chemical evidence of iron deficiency or hemolysis. Both ACE.1 and ACE.2 mice have equally low serum angiotensin II levels with a significant elevation of serum angiotensin I and the stem cell inhibitory peptide AcSDKP. Due to the presence of renal failure in ACE.1 mice, we have characterized in detail the anemia of ACE.2 mice. These animals demonstrate a significant reduction in total circulating red cell mass (24.2 +/- 1.1 μl/g vs 31.7 +/- 1.8 μl/g for wild type mice) without a change in total blood volume (57.8 +/- 1.2 μl/g vs 56.0 +/- 5.0 μl/g for wild type mice) as measured by the infusion of 51 Cr labeled erythrocytes. ACE.2 mice also have an increase in total plasma volume as determined by Evans Blue Dye infusion. The administration of angiotensin II to ACE.2 knockouts significantly increases their hematocrit and serum hemoglobin. Conclusion: The finding of significant anemia in ACE.2 mice, animals without renal failure, suggests a previously unappreciated role of the renin-angiotensin system in regulating erythropoiesis.

Evaluation of Anemia in Angiotensin Converting Enzyme (ACE) Knockout Mice.

P2 Using targeted homologous recombination, we made two lines of mice that lack ACE. ACE.1 mice are null for all ACE activity while ACE.2 mice lack tissue ACE but retain 1/3 normal plasma ACE activity. Both strains have a marked decrease in blood pressure and are unable to produce a concentrated urine. ACE.1 mice have renal failure, as measured by a reduced creatinine clearance and an elevated serum creatinine, when compared to wild type mice; ACE.2 mice have no evidence of renal failure as indicated by a normal serum creatinine and creatine clearance. Surprisingly, both ACE.1 and ACE.2 mice are anemic with a reduction in hematocrit (38.5 +/- 1.3% and 38.3 +/- 0.8% respectively vs 48.4 +/- 0.9% for wild type) and serum hemoglobin (12.0 +/- 0.3 mg/dl and 11.7 +/- 0.2 mg/dl vs 14.7 +/- 0.3 mg/dl for wild type). In both strains, serum erythropoietin is elevated. Neither strain differs from wild type in regard to MCV, MCH, or MCHC, nor does either strain show chemical evidence of iron deficiency or hemolysis. Both ACE.1 and ACE.2 mice have equally low serum angiotensin II levels with a significant elevation of serum angiotensin I and the stem cell inhibitory peptide AcSDKP. Due to the presence of renal failure in ACE.1 mice, we have characterized in detail the anemia of ACE.2 mice. These animals demonstrate a significant reduction in total circulating red cell mass (24.2 +/- 1.1 μl/g vs 31.7 +/- 1.8 μl/g for wild type mice) without a change in total blood volume (57.8 +/- 1.2 μl/g vs 56.0 +/- 5.0 μl/g for wild type mice) as measured by the infusion of 51 Cr labeled erythrocytes. ACE.2 mice also have an increase in total plasma volume as determined by Evans Blue Dye infusion. The administration of angiotensin II to ACE.2 knockouts significantly increases their hematocrit and serum hemoglobin. Conclusion: The finding of significant anemia in ACE.2 mice, animals without renal failure, suggests a previously unappreciated role of the renin-angiotensin system in regulating erythropoiesis.

Determinants Of The Pulmonary Input Impedance Spectrum: Theoretical Considerations Based On A Mathematical Model

The determinants of the shape of the pulmonary input impedance spectrum were investigated using a mathematical model based on Womersley’s equations for pulsatile flow in constrained viscoelastic tubes and structural data (morphometry, elasticity, and rheology) provided for the entire cat lung by Zhuang et al. Mean distending pressures and diameters of vessels were determined from the struc-tured data and four independent variables: cardiac output and left atrial, pleural, and alveolar pressures. Studies were performed in a control model and a model whose structure was designed to imitate that of a subject with pulmonary vascular impairment. Model simplifications were investigated. Increasing left atrial pressure or cardiac output caused passive distention of vessels that increased total blood volume and decreased vascular resistance, creating a slight spectral shift downward and to the right. Increasing pleural pressure decreased total blood volume and increased vascular resistance, creating a spectral shift upward and to the right. Increasing levels of alveolar pressure resulted in increased vascular resistance and pressures find a shift in blood volume from the capillaries to the arteries without significant change in total blood volume, creating a spectral shift that was slightly downward and to the right. Model simplification studies demonstrated that (1) all vessels distal to the tenth generation (arteries with zero distending pressure diameters < 50 μM) can be modelled as a simple resistor or (2) all vessels distal to the fourth generation can be modelled as a modified Windkessel. Results obtained from the passive studies were consistent with those obtained from normal lambs and lam be with chronically elevated pulmonary blood flow. To model a hypertensive state created by ifljury to the lung microvasculature, the number and size of small vessels and the compliance constants of all arteries were decreased and the viscoelastic constant was increased, which created the requisite shift to the right and upward. To better match the modulus fluctuation and negative phase angles at higher frequencies in the hypertensive animals, the development of a major reflection site between the main and branch arteries was hypothesized.

Determination of total effective vascular compliance in patients with sepsis syndrome.

Changes in capacitance vessels have important consequences on cardiac filling pressure and fluid volume distribution in patients with sepsis syndrome. Vascular compliance may be evaluated from the slope of the relationship between changes in total blood volume (deltaTBV) and changes in central venous pressure (deltaCVP) during acute volume expansion (450 ml of gelatin fluid over 6 min), i.e., from the deltaTBV/deltaCVP ratio. The mean ratio (ml x mm Hg-1 x kg-1) was 2.03 +/- 0.21 in control subjects, 1.43 +/- 0.25 in mechanically ventilated patients without sepsis syndrome, and 0.94 +/- 0.24 in mechanically ventilated patients with sepsis syndrome (p < 0.0001 versus the other two groups). Based on echocardiographic determinations, cardiac performance was constantly found within the normal range (cardiac output ranged from 5.6 +/- 1.2 to 6.7 +/- 2.0 L/min in nonseptic patients from 6.8 +/- 1.9 to 7.8 +/- 2.2 in septic patients). Effective compliance of the total vascular bed is therefore reduced in patients with sepsis syndrome, independently of the hemodynamic modifications due to mechanical ventilation.

Destruction of newly released red blood cells in space flight.

Space flight results in a rapid change in total blood volume, plasma volume, and red blood cell mass because the space to contain blood is decreased. The plasma volume and total blood volume decreases during the first hours in space and remain at a decreased level for the remainder of the flight. During the first several hours following return to earth, plasma volume and total blood volume increase to preflight levels. During the first few days in space recently produced red blood cells disappear from the blood resulting in a decrease in red blood cell mass of 10-15%. Red cells 12 d old or older survive normally and production of new cells continues at near preflight levels. After the first few days in space, the red cell mass is stable at the decreased level. Following return to earth the hemoglobin and red blood cell mass concentrations decrease reflecting the increase in plasma volume. The erythropoietin levels increase responding to "postflight anemia"; red cell production increases, and the red cell mass is restored to preflight levels after several weeks.