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Monitoring of continuous blood pressure and cardiac output is important to prevent hypoperfusion and to guide fluid administration, but only few patients receive such monitoring due to the invasive nature of most of the methods presently available. Noninvasive blood pressure can be determined continuously using finger cuff technology and cardiac output is easily obtained using a pulse contour method. In this way completely noninvasive continuous blood pressure and cardiac output are available for clinical use in all patients that would otherwise not be monitored. Developments and state of art in hemodynamic monitoring are reviewed here, with a focus on noninvasive continuous hemodynamic monitoring form the finger. [ABSTRACT FROM AUTHOR]

Purpose: Many patients remain unsatisfied after total knee arthroplasty (TKA). Personalized alignment strategies have gained popularity in the search to improve patient satisfaction and function. This study aimed to examine the impact of limb overcorrection in the coronal plane on patient satisfaction and functional outcome. The secondary aim was to investigate how a change in knee phenotype following TKA affects clinical outcome., Methods: A retrospective matched case-control study was designed between patients with limb overcorrection (N = 37) and a control group (N = 104). Mean follow-up was 68 months. Satisfaction and function were compared by means of the new 2011 Knee Society Score (KSS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Radiological evaluation was performed on weight-bearing full-leg radiographs. Overcorrection was defined as a mechanical HKA (mHKA) angle of 2° or more and opposite to the preoperative alignment. The control group consisted of TKAs that were corrected to neutral or left in slight undercorrection. Finally, component alignment (lateral distal femoral angle (LDFA) and medial proximal tibial angle (MPTA)) and Coronal Plane Alignment of the knee (CPAK) phenotypes were evaluated., Results: The overcorrection group performed better than the control group in terms of KSS subscores satisfaction and functional activities, total KSS score, all KOOS subcategories, and total KOOS score. Subdivision of the control group into a neutral and undercorrection group, and the overcorrection group into mild and severe overcorrection, revealed similar findings.A chance in knee phenotype as per aHKA, JLO or CPAK did not result in worse clinical outcomes., Conclusion: Accidental limb overcorrection after TKA does not result in inferior clinical outcomes or patient satisfaction at midterm follow-up.The present study could not identify an optimal coronal alignment target. This suggests that coronal alignment as a predictor of patient satisfaction and function is likely less important than previously believed., Level of Evidence: Level III, retrospective case-control study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: Lateral extra-articular tenodesis (LET) procedure, combined with an intra-articular reconstruction of the anterior cruciate ligament (ACL), is used to reduce rotational laxity and the risk of graft failure. However, concern of overtightening of the lateral compartment and subsequent osteoarthritis remains. The aim of this study is to evaluate the degenerative changes in the lateral compartment and to compare the clinical and radiographical results between two LET techniques., Methods: Eighty-three patients (86 knees) were retrospectively reviewed at a mean of 67.7 months (range 49-85 months). Forty-two knees had an ACL reconstruction combined with a LET procedure according to the modified Lemaire technique and 44 knees according to the modified Coker-Arnold technique. IKDC, Lysholm, Tegner and VAS scores were used. Osteoarthritis was radiographically evaluated by the Kellgren-Lawrence classification., Results: There were 12 patients (28.6%) in the modified Lemaire subgroup and 13 patients (29.5%) in the modified Coker-Arnold subgroup that had doubtful or mild radiologic signs of osteoarthritis. No patients had moderate or severe signs at final follow-up. There was no significant difference in radiological signs of osteoarthritis. In the modified Lemaire subgroup, we report a mean IKDC of 86.31 (± 13.794), a mean Lysholm of 87.83 (± 12.802) and a mean Tegner of 5.38 (± 2.556). In the modified Coker-Arnold subgroup, a mean IKDC of 87.27 (± 11.653), a mean Lysholm of 91.89 (± 8.035) and a mean Tegner of 5.16 (± 2.420) were reported. There were no statistical significant differences between both techniques. In eight patients, a complication was identified, 3 of which had a failure of the ACL reconstruction., Conclusions: The chosen LET-technique seems to have minimal effect on both the clinical and the radiographic results. The LET is a safe procedure, and it does not increase the risk of osteoarthritis in the lateral compartment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Osteoarthritis is a highly prevalent disease affecting the hip and knee joint and is characterized by load-mediated pain and decreased quality of life. Dependent on involved joint, patients present antalgic movement compensations, aiming to decrease loading on the involved joint. However, the associated alterations in mechanical loading of the ipsi- and contra-lateral lower limb joints, are less documented. Here, we documented the biomechanical fingerprint of end-stage hip and knee osteoarthritis patients in terms of ipsilateral and contralateral hip and knee loading during walking and stair ambulation., Methods: Three-dimensional motion-analysis was performed in 20 hip, 18 knee osteoarthritis patients and 12 controls during level walking and stair ambulation. Joint contact forces were calculated using a standard musculoskeletal modelling workflow in Opensim. Involved and contralateral hip and knee joint loading was compared against healthy controls using independent t-tests (p < 0.05)., Findings: Both hip and knee cohorts significantly decreased loading of the involved joint during gait and stair ambulation. Hip osteoarthritis patients presented no signs of ipsilateral knee nor contralateral leg overloading, during walking and stair ascending. However, knee osteoarthritis patients significantly increased loading at the ipsilateral hip, and contralateral hip and knee joints during stair ambulation compared to controls., Interpretation: The biomechanical fingerprint in knee and hip osteoarthritis patients confirmed antalgic movement strategies to unload the involved leg during gait. Only during stair ambulation in knee osteoarthritis patients, movement adaptations were confirmed that induced unbalanced intra- and inter-limb loading conditions, which are known risk factors for secondary osteoarthritis., Competing Interests: Declaration of Competing Interest All authors hereby declare that there are no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The purpose of this study was to determine the learning curve for total operative time using a novel cutting guide positioning robotic assistant for total knee arthroplasty (raTKA). Additionally, we compared complications and final limb alignment between raTKA and manual TKA (mTKA), as well as accuracy to plan for raTKA cases., Methods: We performed a retrospective cohort study on a series of patients (n = 180) that underwent raTKA (n = 90) using the ROSA Total Knee System or mTKA (n = 90) by one of three high-volume (> 200 cases per year) orthopaedic surgeons between December 2019 and September 2020, with minimum three-month follow-up. To evaluate the learning curve surgical times and postoperative complications were reviewed., Results: The cumulative summation analysis for total operative time revealed a change point of 10, 6, and 11 cases for each of three surgeons, suggesting a rapid learning curve. There was a significant difference in total operative times between the learning raTKA and both the mastered raTKA and mTKA groups (p = 0.001) for all three surgeons combined. Postoperative complications were minimal in all groups. The proportion of outliers for the final hip-knee-ankle angle compared to planned was 5.2% (3/58) for the mastered raTKA compared to 24.1% (19/79) for mTKA (p = 0.003). The absolute mean difference between the validated and planned resections for all angles evaluated was < 1 degree for the mastered raTKA cases., Conclusion: As the digital age of medicine continues to develop, advanced technologies may disrupt the industry, but should not disrupt the care provided. This cutting guide positioning robotic system can be integrated relatively quickly with a rapid initial learning curve (6-11 cases) for operative times, similar 90-day complication rates, and improved component positioning compared to mTKA. Proficiency of the system requires additional analysis, but it can be expected to improve over time., Level of Evidence: Level III Retrospective Therapeutic Cohort Study., (© 2021. The Author(s).)

Objectives: The primary objective of the study was to investigate rehabilitation strategies of Flemish physical therapists before and after anterior cruciate ligament (ACL) reconstruction. Secondly, we aimed to investigate physical therapists' preferences on continuing education and evaluate their self-rated confidence and competence when treating patients before and after ACL reconstruction., Design: Survey-based study., Setting: Online survey platform., Participants: Flemish physical therapists (n = 283)., Main Outcome Measures: The online survey consisted of a combination of 40 open- and closed-ended questions, divided across 5 sections: (1) participant demographics and clinical practice information, (2) patient population information, (3) continued education practices, (4) rehabilitation strategies, and (5) physical therapist self-rated confidence and competence to treat patients with ACL reconstruction., Results: A wide variability in rehabilitation strategies were found across the whole ACL rehabilitation continuum, which were in general not in line with best available evidence. Nevertheless, the overall self-rated confidence and competence of physical therapists treating patients before and after ACL reconstruction were high., Conclusion: Our findings indicate a need to improve rehabilitation practices before and after ACL reconstruction. Advanced research dissemination and implementation are required to achieve better rehabilitation outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A new technique for combined anterior cruciate ligament and anterolateral ligament reconstructions is described. An iliotibial band strip is used as an ALL graft , leaving the distal insertion intact and fix it with a knotless anchor on the femoral origin, after tunneling it under the lateral collateral ligament.

Background: Apart from biomechanical alterations in movement patterns, it is known that movement limitations in persons with knee osteoarthritis (PwKOA) are related to an individual's perception and belief regarding pain and disability. To gain more insights into the functional movement behaviour of PwKOA in a clinical setting, inertial sensor technology can be applied. This study first aims to evaluate the ability of inertial sensors to discriminate between healthy controls (HC) and PwKOA. Secondly, this study aims to determine the relationship between movement behaviour, pain-related factors and disability scores., Methods: Twelve HC and 19 PwKOA were included. Five repetitions of six functional movement tasks (walking, forward lunge, sideward lunge, ascent and descent stairs, single leg squat and sit-to-stand) were simultaneously recorded by the inertial sensor system and a camera-based motion analysis system. Statistically significant differences in angular waveforms of the trunk, pelvis and lower limb joints between HC and PwKOA were determined using one-dimensional statistical parametric mapping (SPM1D). The Knee injury and Osteoarthritis Outcome Score and TAMPA scale for Kinesiophobia were used to evaluate the relationship between discriminating joint motion, pain-related factors and disability using spearman's correlation coefficients., Results: PwKOA had significantly less trunk rotation, internal pelvis rotation and knee flexion ROM during walking. Additionally, the reduced knee flexion (i.e. at the end of the stance phase and swing phase) was related to increased level of perceived pain. During the sideward lunge, PwKOA had significantly less knee flexion, ankle plantarflexion and hip abduction. This decreased hip abduction (i.e. during stance) was related to higher fear of movement. Finally, PwKOA had significantly less knee flexion during the forward lunge, single leg squat and during ascent and descent stairs. No significant correlations were observed with disability., Conclusions: Inertial sensors were able to discriminate between movement characteristics of PwKOA and HC. Additionally, significant relationships were found between joint motion, perceived pain and fear of movement. Since inertial sensors can be used outside the laboratory setting, these results are promising as they indicate the ability to evaluate movement deviations. Further research is required to enable measurements of small movement deviations in clinically relevant tasks.

Purpose  The aim of this retrospective, multicenter study was to investigate the correlation between a high degree of rotatory instability, posterolateral tibial slope (PLTS), and anterolateral ligament (ALL) injury. Methods  The study population consisted of 76 adults with isolated, complete noncontact anterior cruciate ligament (ACL) tear. The sample was divided into two groups according to the preoperative degree of rotator instability (group A: pivot-shift test grades 2 and 3; group B: pivot-shift test grade 1). Preoperative magnetic resonance imaging (MRI) assessment included angle of PLTS, posterior shift of the lateral femoral condyle (16 mm) on the tibial plateau, and the presence/absence of ALL injury. The two groups were compared for differences. Results  There was a statistically significant association between pivot-shift test grades 2 and 3 (group A), PLTS slope angle > 9 degrees, and ALL injury ( p  < 0.05). Group A also demonstrated a greater posterior shift of lateral femoral condyle (>11 mm), which was, however, not statistically significant when evaluated as an isolated variable. Conclusion  Our study indicates that an increased PLTS is associated with an increased incidence of ALL injury and an increased grade of pivot shift in patients with ACL tear. Assessment of posterolateral tibial slope on MRI can therefore play a key adjunct role in the surgical planning of ALL reconstruction, especially in cases when ALL damage is radiologically difficult to detect or doubtful. Level of Evidence  This is a retrospective comparative level III study., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Single-leg hop tests are commonly performed in the forward direction to evaluate functional performance. However, athletes move in multiple directions during pivoting sports. The first aim of this study was to examine test-retest reliability of single-leg hop tests in the forward, medial and rotational direction in non-injured athletes. Second, the discriminative ability to detect leg asymmetries with these hop tests in anterior cruciate ligament (ACL) reconstructed athletes was determined., Methods: Sixteen recreational non-injured participants (eight females, eight males; 22.4 ± 1.9 years) were tested twice (one-week interval) and performed the single hop for distance (SH), triple hop for distance (TH), medial side triple hop for distance (MSTH) and 90° medial rotation hop for distance (MRH). Intraclass correlation coefficients (ICCs), standard errors of measurement (SEM) and smallest detectable differences (SDD) were calculated. Discriminative ability was determined in 32 ACL-reconstructed participants (four females, 28 males; 24.4 ± 4.6 years; six months postoperative) who performed the same hop tests once., Results: The ICCs ranged between 0.93 and 0.98. The SEM and SDD were respectively 2.6-4.1% and 7.2-11.3% of the mean hop distance of the group. The proportion (%) of ACL-reconstructed participants passing the ≥90% limb symmetry cut-off was 62.5 (SH), 59.4 (TH), 40.6 (MSTH) and 46.9 (MRH)., Conclusion: Excellent test-retest reliability of forward, medial and rotational hop tests was found. This allows clinicians to make informed interpretations of changes in hop test distances when retesting athletes. Medial and rotational hop tests are more likely to show limb asymmetries in ACL-reconstructed participants compared to forward hop tests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Self-measurement of blood pressure (BP) is increasingly being used for the diagnosis of hypertension and to monitor BP at home. Whenever compared with ambulatory BP measurements, home BP values are frequently higher and less predictive for incident cardiovascular events. We hypothesized that this could be caused by a pressor response elicited by the self-measurement of BP., Methods: A total of 50 patients (mean age 62.0 ± 11.2 years, 44% women) were included, 25 with and 25 without at least 10/5 mmHg higher home BP compared with daytime ambulatory BP. All patients performed 10 consecutive oscillometric BP measurements after 10 min of rest, followed by another resting period of 10 min, while continuously monitoring BP and central hemodynamics using finger photoplethysmography. Baseline BP before the start of the self-measurements was compared with the average BP during the first 10 s of inflation of the cuff., Results: In both groups, we observed a significant increase in SBP and DBP during cuff inflation. The mean rise in average BP was 6.9 ± 6.3/4.5 ± 4.3 mmHg in the group with and 4.4 ± 9.4/2.7 ± 5.3 mmHg in the group without a BP difference between home and daytime ambulatory BP compared with baseline, whereas the maximum increase in average BP was 17.4/8.4 mmHg and 17.7/7.5 mmHg (P < 0 01). The increase in BP coincided with an increase in heart rate and cardiac output. BP differences attenuated after multiple readings, but did not disappear., Conclusion: Our results support the existence of a pressor response during self-BP measurement that remains present after multiple BP readings.

Blood pressure (BP) decreases in the first weeks after Roux-and-Y gastric bypass surgery. Yet the pathophysiology of the BP-lowering effects observed after gastric bypass surgery is incompletely understood. We evaluated BP, systemic hemodynamics, and baroreflex sensitivity in 15 obese women[mean age 42 ± 7 standard deviation (SD) yr, body mass index 45 ± 6 kg/m 2 ] 2 wk before and 6 wk following Roux-and-Y gastric bypass surgery. Six weeks after gastric bypass surgery, mean body weight decreased by 13 ± 5 kg (10%, P < 0.001). Office BP decreased from 137 ± 10/86 ± 6 to 128 ± 12/81 ± 9 mmHg (P < 0.001, P < 0.01), while daytime ambulatory BP decreased from 128 ± 14/80 ± 9 to 114 ± 10/73 ± 6 mmHg (P = 0.01, P = 0.05), whereas nighttime BP decreased from 111 ± 13/66 ± 7 to 102 ± 9/62 ± 7 mmHg (P = 0.04, P < 0.01). The decrease in BP was associated with a 1.6 ± 1.2 l/min (20%, P < 0.01) decrease in cardiac output (CO), while systemic vascular resistance increased (153 ± 189 dyn·s·cm -5 , 15%, P < 0.01). The maximal ascending slope in systolic blood pressure decreased (192 mmHg/s, 19%, P = 0.01), suggesting a reduction in left ventricular contractility. Baroreflex sensitivity increased from 9.0 [6.4-14.3] to 13.8 [8.5-19.0] ms/mmHg (median [interquartile range]; P < 0.01) and was inversely correlated with the reductions in heart rate (R = -0.64, P = 0.02) and CO (R = -0.61, P = 0.03). In contrast, changes in body weight were not correlated with changes in either BP or CO. The BP reduction following Roux-and-Y gastric bypass surgery is correlated with a decrease in CO independent of changes in body weight. The contribution of heart rate to the reduction in CO together with enhanced baroreflex sensitivity suggests a shift toward increased parasympathetic cardiovascular control., New & Noteworthy: The reason for the decrease in blood pressure (BP) in the first weeks after gastric bypass surgery remains to be elucidated. We show that the reduction in BP following surgery is caused by a decrease in cardiac output. In addition, the maximal ascending slope in systolic blood pressure decreased suggesting a reduction in left ventricular contractility and cardiac workload. These findings help to understand the physiological changes following gastric bypass surgery and are relevant in light of the increased risk of heart failure in these patients., (Copyright © 2017 the American Physiological Society.)

Background: The objective of this study was to describe changes in cerebral tissue oxygen saturation (SctO2) due to changes in body position in healthy volunteers and in patients undergoing surgery under general anesthesia in the beach chair position (BCP) and lateral decubitus position (LDP)., Methods: In this prospective observational study, SctO2 was measured in 85 awake volunteers serially positioned every 15 min, beginning with the supine position (SP) and followed by the beach chair, supine, and lateral decubitus positions. Cerebral tissue oxygen saturation was also measured supine and in either the BCP or the LDP in 195 patients (according to surgical preference) undergoing elective arthroscopic shoulder surgery. We measured the lowest stable SctO2 values in each position as well as changes in blood pressure and heart rate., Results: In healthy volunteers, the median (interquartile range [IQR]) lowest stable SctO2 value in the SP was 69 [66-71] %. A change in position to the BCP caused a small but statistically significant decrease in the median [IQR] lowest SctO2 value to 67 [65-70] % (P = 0.028 compared with baseline). This decrease was associated with an increase in median [IQR] arterial pressure from 83 [78-88] mmHg in the SP to 85 [81-93] mmHg in the BCP (P < 0.001 compared with baseline). In patients undergoing surgery in the BCP, the median [IQR] lowest stable SctO2 value was 55 [51-59] %, which was significantly lower (P < 0.001) than the median [IQR] lowest SctO2 value in patients in the LDP (66 [62-69] %). More patients in the BCP group (57%) showed SctO2 values ≤ 55% and/or a decrease of ≥ 20% from baseline (57%) compared with the LDP group (5% and 6%, respectively; P < 0.001 for each comparison)., Conclusions: More than 55% of patients undergoing arthroscopic shoulder surgery in the BCP experience cerebral desaturation events. In volunteers without anesthesia, no desaturation events were observed. The clinical importance of these findings needs further investigation.

Type 2 diabetes mellitus is associated with microvascular complications, hypertension, and impaired dynamic cerebral autoregulation. Intensive blood pressure (BP) control in hypertensive type 2 diabetic patients reduces their risk of stroke but may affect cerebral perfusion. Systemic hemodynamic variables and transcranial Doppler-determined cerebral blood flow velocity (CBFV), cerebral CO2 responsiveness, and cognitive function were determined after 3 and 6 months of intensive BP control in 17 type 2 diabetic patients with microvascular complications (T2DM+), in 18 diabetic patients without (T2DM-) microvascular complications, and in 16 nondiabetic hypertensive patients. Cerebrovascular reserve capacity was lower in T2DM+ versus T2DM- and nondiabetic hypertensive patients (4.6±1.1 versus 6.0±1.6 [P<0.05] and 6.6±1.7 [P<0.01], Δ%mean CBFV/mm Hg). After 6 months, the attained BP was comparable among the 3 groups. However, in contrast to nondiabetic hypertensive patients, intensive BP control reduced CBFV in T2DM- (58±9 to 54±12 cm·s(-1)) and T2DM+ (57±13 to 52±11 cm·s(-1)) at 3 months, but CBFV returned to baseline at 6 months only in T2DM-, whereas the reduction in CBFV progressed in T2DM+ (to 48±8 cm·s(-1)). Cognitive function did not change during the 6 months. Static cerebrovascular autoregulation appears to be impaired in type 2 diabetes mellitus, with a transient reduction in CBFV in uncomplicated diabetic patients on tight BP control, but with a progressive reduction in CBFV in diabetic patients with microvascular complications, indicating that maintenance of cerebral perfusion during BP treatment depends on the progression of microvascular disease. We suggest that BP treatment should be individualized, aiming at a balance between BP reduction and maintenance of CBFV.

Although a relation between diminished human immunity and stress is well recognized both within the general public and the scientific literature, the molecular mechanisms by which stress alters immunity remain poorly understood. We explored a novel model for acute human stress involving volunteers performing a first-time bungee jump from an altitude of 60 m and exploited this model to characterize the effects of acute stress in the peripheral blood compartment. Twenty volunteers were included in the study; half of this group was pretreated for 3 d with the β-receptor blocking agent propranolol. Blood was drawn 2 h before, right before, immediately after and 2 h after the jump. Plasma catecholamine and cortisol levels increased significantly during jumping, which was accompanied by significantly reduced ex vivo inducibility of proinflammatory cytokines as well as activation of coagulation and vascular endothelium. Kinome profiles obtained from the peripheral blood leukocyte fraction contained a strong noncanonical glucocorticoid receptor signal transduction signature after jumping. In apparent agreement, jumping down-regulated Lck/Fyn and cellular innate immune effector function (phagocytosis). Pretreatment of volunteers with propranolol abolished the effects of jumping on coagulation and endothelial activation but left the inhibitory effects on innate immune function intact. Taken together, these results indicate that bungee jumping leads to a catecholamine-independent immune suppressive phenotype and implicate noncanonical glucocorticoid receptor signal transduction as a major pathway linking human stress to impaired functioning of the human innate immune system.

Acute psychological stress challenges the cardiovascular system with an increase in BP (blood pressure), HR (heart rate) and reduced BRS (baroreflex sensitivity). β-adrenergic blockade enhances BRS during rest, but its effect on BRS during acute psychological stress is unknown. This study tested the hypothesis that BRS is higher during acute psychological stress in healthy subjects under β-adrenergic blockade. Twenty healthy novice male bungee jumpers were randomized and studied with (PROP, n=10) or without (CTRL, n=10) propranolol. BP and HR responses and BRS [cross-correlation time-domain (BRSTD) and cross-spectral frequency-domain (BRSFD) analysis] were evaluated from 30 min prior up to 2 h after the jump. HR, cardiac output and pulse pressure were lower in the PROP group throughout the study. Prior to the bungee jump, BRS was higher in the PROP group compared with the CTRL group [BRSTD: 28 (24-42) compared with 17 (16-28) ms·mmHg-1, P<0.05; BRSFD: 27 (20-34) compared with 14 (9-19) ms·mmHg-1, P<0.05; values are medians (interquartile range)]. BP declined after the jump in both groups, and post-jump BRS did not differ between the groups. In conclusion, during acute psychological stress, BRS is higher in healthy subjects treated with non-selective β-adrenergic blockade with significantly lower HR but comparable BP.

The Frank-Starling mechanism describes the relationship between stroke volume and preload to the heart, or the volume of blood that is available to the heart--the central blood volume. Understanding the role of the central blood volume for cardiovascular control has been complicated by the fact that a given central blood volume may be associated with markedly different central vascular pressures. The central blood volume varies with posture and, consequently, stroke volume and cardiac output (Q) are affected, but with the increased central blood volume during head-down tilt, stroke volume and Q do not increase further indicating that in the supine resting position the heart operates on the plateau of the Frank-Starling curve which, therefore, may be taken as a functional definition of normovolaemia. Since the capacity of the vascular system surpasses the blood volume, orthostatic and environmental stress including bed rest/microgravity, exercise and training, thermal loading, illness, and trauma/haemorrhage is likely to restrict venous return and Q. Consequently the cardiovascular responses are determined primarily by their effect on the central blood volume. Thus during environmental stress, flow redistribution becomes dependent on sympathetic activation affecting not only skin and splanchnic blood flow, but also flow to skeletal muscles and the brain. This review addresses the hypothesis that deviations from normovolaemia significantly influence these cardiovascular responses.

Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxide-bioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO2 responsiveness is nitric oxide dependent and has been related to an increased stroke risk in microvascular diseases. We questioned whether cerebrovascular CO2 responsiveness is impaired in SCD and related to hemolytic anemia. Transcranial Doppler-determined mean cerebral blood flow velocity (V(mean)), near-infrared spectroscopy-determined cerebral oxygenation, and end-tidal CO2 tension were monitored during normocapnia and hypercapnia in 23 patients and 16 control subjects. Cerebrovascular CO2 responsiveness was quantified as Delta% V(mean) and Deltamicromol/L cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin per mm Hg change in end-tidal CO2 tension. Both ways of measurements revealed lower cerebrovascular CO2 responsiveness in SCD patients versus controls (V(mean), 3.7, 3.1-4.7 vs 5.9, 4.6-6.7 Delta% V(mean) per mm Hg, P < .001; oxyhemoglobin, 0.36, 0.14-0.82 vs 0.78, 0.61-1.22 Deltamicromol/L per mm Hg, P = .025; deoxyhemoglobin, 0.35, 0.14-0.67 vs 0.58, 0.41-0.86 Deltamicromol/L per mm Hg, P = .033; total-hemoglobin, 0.13, 0.02-0.18 vs 0.23, 0.13-0.38 Deltamicromol/L per mm Hg, P = .038). Cerebrovascular CO2 responsiveness was not related to markers of hemolytic anemia. In SCD patients, impaired cerebrovascular CO2 responsiveness reflects reduced cerebrovascular reserve capacity, which may play a role in pathophysiology of stroke.