Blood Volume Shifts Research Articles

An Optimal Control Approach to Modeling the Cardiovascular-Respiratory System: An Application to Orthostatic Stress

This paper introduces a model designed to study the cardiovascular-respiratory system and its control features. It has been previously applied to study several physiological situations and in this paper it will be applied to the simulation of the phenomenon of orthostatic stress. Orthostatic stress refers to stress placed on the cardiovascular system when the body is in the upright position as compared to the supine position. The model consists of cardiovascular and respiratory components and includes cardiovascular autoregulation, ventilation control, and the baroreflex loop. Instead of an explicit formula for calculating the control response from the pressures and blood gases, we use an optimal control. Steady state and dynamic model simulation is compared with experimental data we have collected using head up tilt (HUT) experiments. The simulations fit the measured data well and represent reasonable physiological values. This work also examines an important issue related to orthostatic stress experiments. The head up tilt experiment (where gravity creates extra pressure stress on the lower body) is to be distinguished from the lower body negative pressure (LBNP) experiment where the lower body is subject to reduced exterior air pressure. Both tests create blood volume shifts to the lower body but the two physiological conditions are not entirely equivalent. We discuss some of these issues and examine several aspects of implementation of orthostatically induced pressures.

Rate response of a closed-loop stimulation pacing system to changing preload and afterload conditions.

Closed-loop stimulation (CLS) is a new sensor concept for rate adaptive pacing measuring changes in the unipolar right ventricular impedance, which correlates to changes of the right ventricular contractility and reflects the autonomic nervous innervation of the heart. Some patients do not tolerate the CLS mode because of inappropriate tachycardia, mainly related to postural changes. This study tested if the rate response of the CLS sensor is influenced not only by myocardial contractility but also by rapid changes in right ventricular filling. In 12 patients (10 men, median age 77 years) with a Biotronik Inos(2)-CLS DDDR pacemaker and 14 controls (13 men, median age 59 years) head-up tilt and handgrip testing was performed to provoke rapid changes in pre- and afterload. Tilting the pacemaker patients resulted in a nonphysiological steep increase of the sensor rate (increase >20 beats/min, peak after 1 minute, return to baseline within 2-3 minutes), which was significantly different from the control group, showing only a slight rise in intrinsic heart rate immediately after tilting. Simultaneously to the rapid increase in sensor rate, the pacemaker patients showed a marked orthostatic decline of systolic blood pressure. During handgripping, heart rate and blood pressure curves were similar in both groups. In patients with this CLS pacemaker, rapid preload reduction during head-up tilting caused an overshooting sensor rate increase, reproducing the authors' clinical observation of postural pacemaker tachycardia in some patients. Consequently, they concluded that the rate response of the CLS pacing system can be inappropriately influenced by rapid shifts of blood volume, affecting right ventricular filling.

Orthostatic challenge reveals impaired vascular resistance control, but normal venous pooling and capillary filtration in familial dysautonomia

Patients with familial dysautonomia (FD) frequently have profound orthostatic hypotension without compensatory tachycardia. Although the aetiology is presumed to be sympathetic impairment, peripheral vascular responses to orthostasis have not been assessed. The aim of this study was to evaluate the control of vascular responses to postural stress in FD patients. Measurements of heart rate, blood pressure, cardiac stroke volume and cardiac output (CO), by impedance cardiography, and calf-volume changes, by impedance plethysmography, were taken from nine FD patients and 11 control subjects while supine and during head-up tilt. During leg lowering, we also assessed the venoarteriolar reflex by measuring skin red-cell flux. Head-up tilting for 10min induced sustained decreases in mean arterial pressure in the FD patients, but not in the controls. Total peripheral resistance (TPR, i.e. mean arterial pressure/CO) increased significantly in the controls (39.8±6.8%), but not in the FD patients. Calf-volume changes during tilting, when normalized for the initial calf volume, did not differ significantly between the patients (4.62±1.99ml·100ml-1) and the controls (3.18±0.74ml·100ml-1). The vasoconstrictor response to limb lowering was present in the patients (47.7±9.0% decrease in skin red-cell flux), but was impaired as compared with the controls (80.7±3.4%) (P<0.05). The impaired vasoconstriction during limb lowering and absent increase of TPR during tilting confirm that orthostatic hypotension in FD is due primarily to a lack of sympathetically mediated vasoconstriction without evidence of abnormally large shifts in blood volume towards the legs during orthostasis. This may be due, in part, to a preserved myogenic response to increased vascular pressure in the dependent vascular beds.

Orthostatic challenge reveals impaired vascular resistance control, but normal venous pooling and capillary filtration in familial dysautonomia.

Patients with familial dysautonomia (FD) frequently have profound orthostatic hypotension without compensatory tachycardia. Although the aetiology is presumed to be sympathetic impairment, peripheral vascular responses to orthostasis have not been assessed. The aim of this study was to evaluate the control of vascular responses to postural stress in FD patients. Measurements of heart rate, blood pressure, cardiac stroke volume and cardiac output (CO), by impedance cardiography, and calf-volume changes, by impedance plethysmography, were taken from nine FD patients and 11 control subjects while supine and during head-up tilt. During leg lowering, we also assessed the venoarteriolar reflex by measuring skin red-cell flux. Head-up tilting for 10 min induced sustained decreases in mean arterial pressure in the FD patients, but not in the controls. Total peripheral resistance (TPR, i.e. mean arterial pressure/CO) increased significantly in the controls (39.8+/-6.8%), but not in the FD patients. Calf-volume changes during tilting, when normalized for the initial calf volume, did not differ significantly between the patients (4.62+/-1.99 ml.100 ml(-1)) and the controls (3.18+/-0.74 ml.100 ml(-1)). The vasoconstrictor response to limb lowering was present in the patients (47.7+/-9.0% decrease in skin red-cell flux), but was impaired as compared with the controls (80.7+/-3.4%) ( P <0.05). The impaired vasoconstriction during limb lowering and absent increase of TPR during tilting confirm that orthostatic hypotension in FD is due primarily to a lack of sympathetically mediated vasoconstriction without evidence of abnormally large shifts in blood volume towards the legs during orthostasis. This may be due, in part, to a preserved myogenic response to increased vascular pressure in the dependent vascular beds.

Effects of induction of anaesthesia with sufentanil and positive-pressure ventilation on the intra- to extrathoracic volume distribution

Background and objective: Induction of general anaesthesia in combination with positive-pressure ventilation is often associated with a significant decrease of arterial pressure. A decreased preload may contribute to this phenomenon. The aim was to investigate whether a change in cardiac filling occurs following the induction of general anaesthesia with sufentanil under typical clinical conditions. Methods: Fifteen patients scheduled for elective coronary bypass grafting were studied immediately before surgery. In addition to standard monitors, a transpulmonary double-indicator dilution technique measured in vivo intrathoracic blood volume, global end-diastolic volume and total circulating blood volume. For induction of anaesthesia 2 μg kg−1 sufentanil was given. Measurements were performed awake and after the induction of anaesthesia, intubation and mechanical ventilation of the lungs. Results: To maintain arterial pressure during the induction period within −20% of baseline pressure, on average 22 ± 6 mL kg−1 crystalloids and 8 ± 6 mL kg−1 colloids were given. Despite these amounts of fluid, cardiac filling was decreased, whereas circulating blood volume increased significantly. Both central venous pressure and pulmonary capillary wedge pressure increased. Conclusions: Induction of general anaesthesia with positive-pressure ventilation is regularly associated with a blood volume shift from intra- to extrathoracic compartments. Even in low-dose opioid monoanaesthesia with sufentanil - often regarded as relatively inert in haemodynamic terms - the phenomenon could be demonstrated as the primary cause of the often-observed decrease of arterial pressure. It seems, therefore, rationally justified to restore cardiac filling by generous administration of intravenous fluids, at least in patients with unaffected cardiac pump function. During induction of anaesthesia, central venous pressure and pulmonary capillary wedge pressure do not reliably indicate cardiac filling.

Shifts in blood volume alter the perception of posture: further evidence for somatic graviception

This article examines the relation between the perception of one's own body position and the distribution of fluid along the subject's spinal ( z-) axis. Two experiments are reported. The first one is a replication of the Vaitl et al. study [J. Psychophysiol. 27 (1997) 99] which has shown that changes in shifts of blood volume into or out of the thoracic cavity induced by lower body positive pressure (LBPP: +30 mmHg) or lower body negative pressure (LBNP: −30 mmHg) exerted on the lower body led subjects to feel tilted head-up or head-down, respectively. The second experiment was designed to differentiate between the influence of the otoliths and of the changes in fluid distribution on the perception of body position by means of a sled centrifuge in combination with LBPP and LBNP. In both experiments, changes in blood distribution within the thoracic cavity were measured by impedance plethysmography. Forty healthy volunteers (17 females) participated in experiment 1. They were positioned on the side (right-ear-down head position) on a tiltable board which the subject and the experimenter could tilt via remote control around the subjects' z-axis. Subjects were asked to rotate the board until they felt they were in a horizontal posture. The results clearly show that the perception of posture is influenced by the shift in blood distribution. During LBNP subjects perceived being tilted head-up, whereas LBPP led them feel tilted head-down. Thus, the results obtained in the 1997 study were replicated. Fourteen males volunteered in experiment 2. They were positioned on the sled on a centrifuge in the same manner as in experiment 1. The sled could be moved via remote control by both the subject and the experimenter. While the centrifuge rotated (ω=2 π times 0.6 rotations per second) the subjects were asked to move the sled until they felt they were in a horizontal position. As in experiment 1, shifts in blood volume were induced by LBPP and LBNP. The distance between the binaural axis (position of the otoliths) and the centrifuge axis served as dependent measure indicating the subjective horizontal position. Due to the additional centrifugal forces exerted on the body the shifts in blood volume were more pronounced than in experiment 1 where only gravitational forces were produced. The changes in the perception of posture were influenced by both the otoliths and the fluid distribution in such a way that both interact in a compensatory manner. These results again corroborate the evidence that afferent inputs from the cardiovascular system play a major role in the perception of the body posture. This phenomenon of graviception needs to be further elucidated with respect to the origins of the afferent inputs and the site and type of graviceptors (mechanoreceptors) involved.

Effect of continuous infusion of prostaglandin E1 on hepatic blood flow

Study Objective: To evaluate the effects of an intravenous infusion of prostaglandin E1 (PGE1) on hepatic blood flow. Design: Prospective clinical study. Setting: University-affiliated hospital. Patients: 16 ASA physical status I and II surgical patients who were scheduled for abdominal surgery. Interventions: Patients were anesthetized with 1% sevoflurane and 66% nitrous oxide. PGE1 0.05 mg/kg/min or PGE1 0.10 mg/kg/min was continuously infused, followed by an infusion of 1000 mL Ringer’s acetate solution. Measurements: The hemodynamic effect of PGE1 was examined using pulse dye densitometry (PDD). A nose probe for PDD was used, and 10 mg indocyanine green (ICG) in 2 mL distilled water was bolus-infused into a central venous catheter for each measurement. Cardiac output (CO), circulating blood volume (CBV), and plasma dye clearance rate (K) were monitored from the dye-densitogram. Hepatic blood flow was estimated using the K and CBV values. Main Results: PGE1 did not increase CBV or CO. Even adding a 1000 mL crystalloid infusion did not expand CBV, whereas mean arterial pressure (MAP) significantly decreased from 91.1 ± 16.5 mmHg to 84.8 ± 13.5 mmHg (PGE1 0.05 μg/kg/min) and 80.6 ± 14.4 mmHg (PGE1 0.10 μg/kg/min ) (p < 0.01 compared with control value), then to 72.0 ± 6.5 mmHg (PGE1 0.10 μg/kg/min + 1000 mL Ringer’s acetate) (p < 0.01 compared with control value). Hepatic blood flow changes were 1.46 ± 0.60 L/min (control), 1.48 ± 0.45 L/min (PGE1 0.05 μg/kg/min), 1.14 ± 0.35 L/min (PGE1 0.10 μg/kg/min), and 1.15 ± 0.19 L/min (PGE1 0.10 μg/kg/min + 1000 mL Ringer’s acetate) (no significant difference, p < 0.05). Hepatic blood flow and K values did not statistically significantly differ at each condition. Conclusions: PGE1 does not affect blood volume shift, CO, or hepatic blood flow.

Efficacy of a Single Oral Dose of Isosorbide 5‐Mononitrate in Normal Dogs and in Dogs with Congestive Heart Failure

Isosorbide 5‐mononitrate (5‐ISMN) was evaluated in normal dogs and dogs with congestive heart failure (CHF) in a randomized, blinded, and placebo‐controlled study. Equilibrium blood pool imaging was used to detect changes in regional blood volume distribution. Six normal dogs were administered placebo, 2, 3, and 4 mg/kg 5‐ISMN PO on separate days with a 1‐week washout period between randomized dosings. Six dogs with CHF were administered placebo or 4 mg/kg 5‐ISMN on separate days with a 1‐week washout period between randomized dosings. Data were collected at baseline and at 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 minutes after dosing. Measured variables included indirect arterial blood pressure (BP), heart rate (HR), packed cell volume (PCV), scintigraphic count rates for normal dogs, and scintigraphic count rates for CHF dogs. Blood for plasma 5‐ISMN concentration determination was collected at 60 minutes. Scintigraphic counts were corrected for decay and expressed as a percentage of the whole. No differences were detected in BP, HR, PCV, thoracic blood volume percentage (TBVP), or abdominal blood volume percentage (ABVP) between placebo and 5‐ISMN in normal dogs at any dose. No differences were detected in TBVP or ABVP between placebo and 5‐ISMN in dogs with CHF. Plasma 5‐ISMN concentration exceeded the minimum therapeutic concentration in all dogs and at all doses 60 minutes after drug administration. Equilibrium blood pool imaging failed to detect a shift in blood volume with oral 5‐ISMN administration at any dose tested in normal dogs and dogs with CHF, despite adequate drug absorption. On the basis of the results of this study, 5‐ISMN may not be beneficial in the treatment of dogs with CHF.

Efficacy of a single oral dose of isorsorbide 5-mononitrate in normal dogs and in dogs with congestive heart failure.

Isosorbide 5-mononitrate (5-ISMN) was evaluated in normal dogs and dogs with congestive heart failure (CHF) in a randomized, blinded, and placebo-controlled study. Equilibrium blood pool imaging was used to detect changes in regional blood volume distribution. Six normal dogs were administered placebo, 2, 3, and 4 mg/kg 5-ISMN PO on separate days with a 1-week washout period between randomized dosings. Six dogs with CHF were administered placebo or 4 mg/kg 5-ISMN on separate days with a 1-week washout period between randomized dosings. Data were collected at baseline and at 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 minutes after dosing. Measured variables included indirect arterial blood pressure (BP), heart rate (HR), packed cell volume (PCV), scintigraphic count rates for normal dogs, and scintigraphic count rates for CHF dogs. Blood for plasma 5-ISMN concentration determination was collected at 60 minutes. Scintigraphic counts were corrected for decay and expressed as a percentage of the whole. No differences were detected in BP, HR, PCV, thoracic blood volume percentage (TBVP), or abdominal blood volume percentage (ABVP) between placebo and 5-ISMN in normal dogs at any dose. No differences were detected in TBVP or ABVP between placebo and 5-ISMN in dogs with CHF Plasma 5-ISMN concentration exceeded the minimum therapeutic concentration in all dogs and at all doses 60 minutes after drug administration. Equilibrium blood pool imaging failed to detect a shift in blood volume with oral 5-ISMN administration at any dose tested in normal dogs and dogs with CHF, despite adequate drug absorption. On the basis of the results of this study, 5-ISMN may not be beneficial in the treatment of dogs with CHF.

Effects of the Sitting Position on the Distribution of Blood Volume in Patients Undergoing Neurosurgical Procedures

The use of the sitting position in neurosurgery is often associated with decreased arterial pressure (MAP) and stroke volume index (SVI). A shift in blood from the intra- to the extrathoracic compartment may be responsible for this cardiovascular response. However, little is known of the amount of shift in blood volume after transfer from the supine to the sitting position. Therefore, we measured simultaneously changes in intrathoracic blood volume (ITBV) caused by a change in body position in anaesthetized patients. Measurements of cardiac index (CI), ITBV, pulmonary (PBV) and total circulating (TBVcirc) blood volumes were performed in the supine and sitting position. CI, ITBV, PBV and TBVcirc were measured using a thermodye dilution technique. Fluid input was restricted to 14 ml kg-1 before induction of anaesthesia. Change in body position caused a significant decrease in ITBV and was accompanied by a significant decrease in CI, SVI and MAP. Changes in ITBV correlated (r = 0.78) with changes in SVI. Thus a change in blood volume distribution between the intra- and extrathoracic compartment occurred after a change from the supine to the sitting position. Indicator dilution enables quantification of this shift and may be helpful in guiding fluid therapy in selected patients.

Body fluid regulation in micro-gravity differs from that on Earth: an overview.

Similar to the response to central hypervolemic conditions on Earth, the shift of blood volume from the legs to the upper part of the body in astronauts entering micro-gravity should, in accordance with the Henry-Gauer mechanism, mediate diuresis and natriuresis. However, fluid balance and kidney function experiments during various space missions resulted in the surprising observation that the responses qualitatively differ from those observed during simulations of hypervolemia on Earth. There is some evidence that the attenuated responses of the kidney while entering weightlessness, and also later during space flight, may be caused by augmented fluid distribution to extravascular compartments compared to conditions on Earth. A functional decoupling of the kidney may also contribute to the observation that renal responses during exposure to micro-gravity are consistently weaker than those during simulation experiments before space flight. Deficits in body mass after landing have always been interpreted as an indication of absolute fluid loss early during space missions. However, recent data suggest that body mass changes during space flight are rather the consequences of hypocaloric nutrition and can be overcome by improved nutrition schemes. Finally, sodium-retaining humoral systems are activated during space flight and may contribute to a new steady-state of metabolic balances with a pronounced increase in body sodium compared to respective conditions on Earth. A revision of the classical "micro-gravity fluid shift" scheme is required.

Effects of the sitting position on the distribution of blood volume in patients undergoing neurosurgical procedures

The use of the sitting position in neurosurgery is often associated with decreased arterial pressure (MAP) and stroke volume index (SVI). A shift in blood from the intra- to the extrathoracic compartment may be responsible for this cardiovascular response. However, little is known of the amount of shift in blood volume after transfer from the supine to the sitting position. Therefore, we measured simultaneously changes in intrathoracic blood volume (ITBV) caused by a change in body position in anaesthetized patients. Measurements of cardiac index (CI), ITBV, pulmonary (PBV) and total circulating (TBVcirc) blood volumes were performed in the supine and sitting position. CI, ITBV, PBV and TBVcirc were measured using a thermodye dilution technique. Fluid input was restricted to 14 ml kg-1 before induction of anaesthesia. Change in body position caused a significant decrease in ITBV and was accompanied by a significant decrease in CI, SVI and MAP. Changes in ITBV correlated (r = 0.78) with changes in SVI. Thus a change in blood volume distribution between the intra- and extrathoracic compartment occurred after a change from the supine to the sitting position. Indicator dilution enables quantification of this shift and may be helpful in guiding fluid therapy in selected patients.

1998 Distinguished Lecture: biomechanics of the microcirculation, an integrative and therapeutic perspective.

The microcirculation, integratively speaking, is distensible and contains 40%-50% of the total blood volume. Other than the mission of mass transport, the microcirculation and its endothelial cells have the role of regulation, signal transduction, proliferation, and repair. In this article, the emphasis is on the integrative role of the microcirculation on circulatory control and its therapeutic role on blood volume compensation. To introduce this topic, I first summarize the morphometry data on the blood volume distribution in the coronary, pulmonary, and mesentery circulation and then review the methodology developed in my laboratory to assess the microvascular volume change or shift of blood volume from microcirculation to macrocirculation. Evidence obtained through these studies indicates that the microcirculation can play a more important role as a reservoir to compensate for blood volume loss than the venous system. Reanalysis of published data also indicates that microvascular pooling, not hypovolemia, is the likely factor causing endotoxin shock or hypotension for hemodialysis patients. Understanding of the role of the microcirculation could lead to more effective diagnosis of cardiovascular deficiency and therapy for hypotension or low cardiac output with intervention through the microcirculation.

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.

Shifts in blood volume alter the perception of posture

Recent experiments have shown that somatic graviceptors exist in humans. Traditionally, extravestibular gravity information has been thought to originate from mechanoreceptors in the joints, muscles and skin. Experiments with normal, paraplegic and nephrectomized subjects revealed that the kidneys and the cardiovascular system are involved in providing truncal gravity information. The present study intends to determine the influence of shifts in body fluid, especially of the distribution of blood along the subjects' spinal (Z-) axis, on the perception of posture. To this end, the distribution of body fluids was altered by means of the technique of lower body negative and positive pressure (LBNP and LBPP). LBNP leads to venous pooling of blood in the legs, whereas LBPP prevents venous blood from pooling, increasing central volume. Changes in blood distribution were measured by segmental impedance cardiography for four body segments: the upper torso (thoracic cavity), lower torso (abdominal and pelvic region), thigh and calf. Seventeen healthy subjects (mean age: 27.3 years) participated in the experiment. They were positioned on the side (right-ear-down head position) on a tilt table which the subjects and the experimenter could tilt via remote control around an axis parallel to the subjects' visual (X-) axis. The experimenter set the initial tilt in total darkness to arbitrary angles, while strictly alternating between head-up and head-down tilts. Subjects were then asked to rotate the board until they felt they were in a horizontal posture. Means and variances of eight pairs of settings were taken as a measure of the subjective horizontal posture (SHP). During LBNP (−30 mmHg), subjects perceived being tilted head-up, whereas LBPP (+30 mmHg) led them to feel tilted head-down. The results corroborate the hypothesis of an effect of the blood's mass on graviception and also indicate supplementary contributions of other visceral afferences. © 1997 Elsevier Science B.V.

Haemodynamic changes during vasodepressor syncope in children and autonomic function.

We investigated postural haemodynamic changes in 24 boys and 30 girls, aged 8-16 years, with orthostatic intolerance. During the orthostatic test, nine boys and seven girls (30%) developed a vasodepressor attack (orthostatic-positive group). The orthostatic-positive group had a more marked increase in heart rate (HR) with slightly lower systolic blood pressure than the orthostatic-negative group during standing, with no significant difference in cardiac output (CO). The shift of blood volume from the intrathoracic region to the lower part of the body determined by electrical impedance and plasma catecholamines on rising were identical in the two groups. At the onset of the vasodepressor attack, CO did not change significantly, indicating that sudden arterial vasodilatation was the cause. In a pharmacological study on autonomic function, higher sensitivity of alpha-adrenoceptor in the resistance vessels was found in the orthostatic-positive group, but there was no significant difference in the basal level of cardiac vagal and sympathetic activity and in cardiac beta-adrenoceptor sensitivity between the two groups. The stepwise regression analysis showed that the magnitude of HR increment during standing was the most useful indicator in predicting the occurrence of a vasodepressor attack. These results suggest that low sympathetic activity in the resistance vessels together with an exaggerated rise in HR during upright posture is strongly associated with vasovagal and vasodepressor attacks in children.

Clinical aspects of the control of plasma volume at microgravity and during return to one gravity.

Plasma volume is reduced by 10-20% within 24-48 h of exposure to simulated or actual microgravity. The clinical importance of microgravity induced hypovolemia is manifested by its relationship with orthostatic intolerance and reduced maximal oxygen uptake (VO2max) after return to one gravity (1G). Since there is no evidence to suggest that plasma volume reduction during microgravity is associated with thirst or renal dysfunctions, a diuresis induced by an immediate blood volume shift to the central circulation appears responsible for microgravity-induced hypovolemia. Since most astronauts choose to restrict their fluid intake before a space mission, absence of increased urine output during actual space flight may be explained by low central venous pressure (CVP) which accompanies dehydration. Compelling evidence suggests that prolonged reduction in CVP during exposure to microgravity reflects a "resetting" to a lower operating point, which acts to limit plasma volume expansion during attempts to increase fluid intake. In ground based and space flight experiments, successful restoration and maintenance of plasma volume prior to returning to an upright posture may depend upon development of treatments that can return CVP to its baseline IG operating point. Fluid-loading and lower body negative pressure (LBNP) have not proved completely effective in restoring plasma volume, suggesting that they may not provide the stimulus to elevate the CVP operating point. On the other hand, exercise, which can chronically increase CVP, has been effective in expanding plasma volume when combined with adequate dietary intake of fluid and electrolytes. The success of designing experiments to understand the physiological mechanisms of and development of effective counter measures for the control of plasma volume in microgravity and during return to IG will depend upon testing that can be conducted under standardized controlled baseline conditions during both ground-based and space flight investigations.

Metabolic responses and mechanisms during water immersion running and exercise.

The low impact nature of exercise in the water has increased interest in this form of exercise and specifically in water running as a cross-training modality. It is used as a possible preventative and therapeutic modality for rehabilitation. The high impact nature of land running predisposes the runner to stress of the lower limbs and overuse injuries. The need to reduce impact, as well as provide a low impact or non-weight-bearing condition for rehabilitation, has led runners and their coaches to the water. This increased interest by coaches and their athletes, attending sports medicine physicians and rehabilitative professionals has stimulated research into water immersion to the neck (WI) running. Exercise in the water has long been used by rehabilitative professionals with patients who have physically debilitating conditions (i.e. arthritis, musculoskeletal disorders) as it provides a medium for even those with limited mobility to exercise and relax their muscles. Numerous comparative studies into WI running from a metabolic as well as a training perspective have been published. WI has also long been used to simulate weightlessness for the comparative study of cardiorespiratory function and thermoregulation. WI and the associated cephalad shift in blood volume has implications on exercise responses during WI running exercise. In addition, the non-weight-bearing nature of WI running also raises issues of the cross-training benefits of WI running. WI running style and prior familiarity with the activity have been found to have a direct relationship with the comparability of WI to land running. This review presents current research into WI running, training specificity and comparative physiology.

Central venous pressure during exercise: role of muscle pump

Central venous pressure (CVP) gives the integral result of changes in cardiac and peripheral factors. Thus, the sudden increase in CVP observed at the onset of dynamic exercise has been attributed to the action of the muscle pump but is also affected by reflex changes in cardiac response. To determine which predominates at the onset of exercise, we compared the change in CVP from rest to onset of upright exercise and after 3 min of exercise in four healthy normal subjects (N) and six patients following heart transplantation (HT), who thus had a delayed cardiac response. CVP immediately increased to a similar extent in both groups at exercise onset (by 4.6 +/- 0.6 mmHg (1 mmHg = 133.3 Pa) in HT and 4.0 +/- 0.4 mmHg in N) (mean +/- SE). After 3 min of exercise, CVP remained constant in N (2.0 +/- 1.1 vs. 2.6 +/- 1.8 at onset) but increased further in HT (7.0 +/- 0.8 vs. 3.5 +/- 1.1 at onset, p < 0.05). The immediate increase in CVP with leg movement in both groups supports an initial central shift in blood volume because of muscle contractions. During the first minute of exercise, muscle blood flow most likely continues to increase and CVP increased further in HT but not in N, which had adequate reflex cardiac adjustment. We conclude that the muscle pump increases CVP at exercise onset, but the interaction between cardiac response and circuit function determines CVP as exercise continues.

General Anesthesia in a Child with a Dynamic, Vascular Anterior Mediastinal Mass

THE patient with an anterior mediastinal mass presents the anesthesiologist with a formidable challenge. Severe respiratory and cardiovascular complications, including the inability to resuscitate, can ensue on induction of general anesthesia. We describe the anesthetic management of a child with a large dynamic vascular malformation located in the neck and mediastinum who underwent percutaneous sclerotherapy.