Enhanced flow-dependent vasodilatation after bed rest, a possible mechanism for orthostatic intolerance in humans

We investigated the alteration in flow-dependent-dilatation in the orthostatic intolerance occurring after bed-rest deconditioning. Eight men [aged mean (SEM) 32 (2) years] underwent two consecutive periods of 7 days of head-down-tilt (HDT, –6°) during bed rest. A control age and sex matched group [n=8, 30 (2) years], maintained its usual physical activity. Blood flow velocity (BFV) and diameter (Doppler and echotracking systems) were measured in the brachial artery, under basal conditions and during the post ischaemic hyperaemia following occlusion. The increase in BFV post-ischaemia did not change before, during and after HDT but the relative increase in the diameter was greater on the 7th day of the HDT period than before HDT [+8.8 (1.6)% compared to +3.7 (1.0)%, P<0.001]. After HDT, 11 of 16 standing tests (comprising eight subjects in the two HDT periods) had to be stopped because of orthostatic intolerance. The flow-dependent-dilatation measured at the end of HDT was negatively correlated with the post-bed-rest duration of orthostatic tolerance (r=0.78, P<0.01). After the sublingual administration of glyceryl trinitrate, there was no change in the increase in diameter. No significant changes were observed in the control group. Bed-rest deconditioning enhances the flow-dependent vasodilatation of large arteries and might contribute to the orthostatic intolerance observed following bed-rest. Electronic Publication     

Femoral to cerebral arterial blood flow redistribution and femoral vein distension during orthostatic tests after 4 days in the head-down tilt position or confinement

The first objective of this study was to confirm that 4 days of head-down tilt (HDT) were sufficient to induce orthostatic intolerance, and to check if 4 days of physical confinement may also induce orthostatic intolerance. Evidence of orthostatic intolerance during tilt-up tests was obtained from blood pressure and clinical criteria. The second objective was to quantify the arterial and venous changes associated with orthostatic intolerance and to check whether abnormal responses to the tilt test and lower body negative pressure (LBNP) may occur in the absence of blood pressure or clinical signs of orthostatic intolerance. The cerebral and lower limb arterial blood flow and vascular resistance, the flow redistribution between these two areas, and the femoral vein distension were assessed during tilt-up and LBNP by ultrasound. Eight subjects were given 4 days of HDT and, 1 month later, 4 days of physical confinement. Tilt and LBNP test were performed pre- and post-HDT and confinement. Orthostatic intolerance was significantly more frequent after HDT (63%) than after confinement (25%, P<0.001). Cerebral haemodynamic responses to tilt-up and LBNP tests were similar pre- and post-HDT or confinement. Conversely, during both tilt and LBNP tests the femoral vascular resistances increased less (P<0.002), and the femoral blood flow reduced less (P<0.001) after HDT than before HDT or after confinement. The cerebral to femoral blood flow ratio increased less after HDT than before (P<0.002) but remained unchanged before and after confinement. This ratio was significantly more disturbed in the subjects who did not complete the tilt test. The femoral superficial vein was more distended during post-HDT LBNP than pre-HDT or after confinement (P<0.01). In conclusion, 4 days of HDT were enough to alter the lower limb arterial vasoconstriction and venous distensibility during tilt-up and LBNP, which reduced the flow redistribution in favour of the brain in all HDT subjects. Confinement did not alter significantly the haemodynamic responses to orthostatic tests. The cerebral to femoral blood flow ratio measured during LBNP was the best predictor of orthostatic intolerance.     

Evaluation of orthostatic regulation by saddle support test using thoracic impedance

We investigated 21 healthy volunteers (10 males and 11 females, mean age 23 +/- 4 years). All the subjects have undergone two 20 min head-up tilt tests using tilt table "TRI W.G. inc." (USA): the first with footplate support and the second with bicycle saddle. Thoracic electrical impedance was measured using impedance cardiography according to Kubicek et al. The protocols included an initial period of 20 min of supine rest while baseline thoracic impedance, blood pressure and heart rate were recorded and then followed by a tilt to 65 degrees. Changes of impedance were measured at min 1, 2, 3, 5, 7, 10, 15, 20 after the procedure. Women had higher values of thoracic impedance both at rest and during the tilt test than men. The value of impedance of the chest negatively correlated with the body mass index. We suppose that an increase of impedance more than 15% may be related with pathological venous pooling. Thoracic impedance may be used to monitor changes of thoracic fluid volumes with posture and possibly to assess orthostatic regulation. The contribution of leg muscles in orthostatic regulation does not reflect values of thoracic impedance.     

Orthostatic stress is necessary to maintain the dynamic range of cardiovascular control in space

In the upright position, gravity fills the low-pressure systems of human circulation with blood and interstitial fluid in the sections below the diaphragm. Without gravity one pressure component in the vessels disappears and the relationship between hydrostatic pressure and oncotic pressure, which regulates fluid passage across the capillary endothelium in the terminal vascular bed, shifts constantly. The visible consequences of this are a puffy face and "bird" legs. The plasma volume shrinks in space and the range of cardiovascular control is reduced. When they stand up for the first time after landing, 30-50% of astronauts suffer from orthostatic intolerance. It remains unclear whether microgravity impairs cardiovascular reflexes, or whether it is the altered volume status that causes the cardiovascular instability following space flight. Lower body negative pressure was used in several space missions to stimulate the cardiovascular reflexes before, during and after a space flight. The results show that cardiovascular reflexes are maintained in microgravity. However, the astronauts' volume status changed in space, towards a volume-retracted state, as measurements of fluid-regulating hormones have shown. It can be hypothesized that the control of circulation and body fluid homeostasis in humans is adapted to their upright posture in the Earth's gravitational field. Autonomic control regulates fluid distribution to maintain the blood pressure in that posture, which most of us have to cope with for two-thirds of the day. A determined amount of interstitial volume is necessary to maintain the dynamic range of cardiovascular control in the upright posture; otherwise orthostatic intolerance may occur more often.     

Proposed role of the paraventricular nucleus in cardiovascular deconditioning

AIM: Cardiovascular deconditioning occurs in individuals exposed to prolonged spaceflight or bedrest and is associated with the development of orthostatic intolerance. Although the precise mechanisms remain to be fully elucidated, astronauts returning from space or bedrest patients returning to normal upright posture present with decreases in plasma volume and alterations in autonomic function. The hindlimb unloaded (HU) rat has been a useful model to study the effects of cardiovascular deconditioning as it mimics many of the changes that occur after spaceflight and bedrest. RESULTS: Experiments performed in HU rats suggest that cardiovascular deconditioning attenuates baroreflex mediated sympathoexcitation and enhances cardiopulmonary receptor mediated sympathoinhibition. These alterations appear to be due to changes in the central nervous system and may contribute to the pre disposition towards orthostatic intolerance associated with cardiovascular deconditioning. The paraventricular nucleus (PVN) of the hypothalamus is important in basal and reflex control of sympathetic outflow. Recent evidence suggests that nitric oxide (NO) is an important inhibitory neurotransmitter in the PVN and that alterations in nitroxidergic transmission in the PVN may be involved in elevated sympathetic tone in certain disease states. CONCLUSION: Based on evidence from other laboratories and published and preliminary data from our own laboratories, this review proposes a role for the PVN in cardiovascular deconditioning. In particular, we discuss the hypothesis that increased NO in the PVN contributes to the altered cardiovascular reflexes observed following deconditioning and how these reflexes may be related to the orthostatic intolerance observed after prolonged spaceflight or bedrest.     

Hemodynamic and neurohumoral responses to the restriction of femoral blood flow by KAATSU in healthy subjects

The application of an orthostatic stress such as lower body negative pressure (LBNP) has been proposed to minimize the effects of weightlessness on the cardiovascular system and subsequently to reduce the cardiovascular deconditioning. The KAATSU training is a novel method to induce muscle strength and hypertrophy with blood pooling in capacitance vessels by restricting venous return. Here, we studied the hemodynamic, autonomic nervous and hormonal responses to the restriction of femoral blood flow by KAATSU in healthy male subjects, using the ultrasonography and impedance cardiography. The pressurization on both thighs induced pooling of blood into the legs with pressure-dependent reduction of femoral arterial blood flow. The application of 200 mmHg KAATSU significantly decreased left ventricular diastolic dimension (LVDd), cardiac output (CO) and diameter of inferior vena cava (IVC). Similarly, 200 mmHg KAATSU also decreased stroke volume (SV), which was almost equal to the value in standing. Heart rate (HR) and total peripheral resistance (TPR) increased in a similar manner to standing with slight change of mean blood pressure (mBP). High-frequency power (HF_RR) decreased during both 200 mmHg KAATSU and standing, while low-frequency/high-frequency power (LF_RR/HF_RR) increased significantly. During KAATSU and standing, the concentration of noradrenaline (NA) and vasopressin (ADH) and plasma renin activity (PRA) increased. These results indicate that KAATSU in supine subjects reproduces the effects of standing on HR, SV, TPR, etc., thus stimulating an orthostatic stimulus. And, KAATSU training appears to be a useful method for potential countermeasure like LBNP against orthostatic intolerance after spaceflight.     

Aortic,cerebral and lower limb arterial and venous response to orthostatic stress after a 60-day bedrest

The objective of this study is to assess by echography and Doppler the Cerebral (Vmca), Aortic (Vao) and Femoral (Vfem) arterial flow velocity and calf vein (Tibial, Gastrocnemius) section (Tib, Gast) during orthostatic intolerance (OI) test after a 60-day, head down tilt bed rest (HDBR). Twenty-four women (25–40 years) underwent a 60-day HDBR at −6°: eight as control (Con), eight with exercise against lower body negative pressure (Ex-Lb) and eight with nutrition supplement (Nut). Before and after (R0) HDBR, all subjects underwent a 10-min, 80° tilt followed by progressive LBNP until presyncope. After the post-HDBR Tilt + LBNP test, two groups were identified: finishers (F, n = 11) who completed the Tilt and non-finishers (NF, n = 13). A higher percentage decrease in Vao flow, higher percentage distension of Tib vein and a lack of increase in Vmca/Vfem ratio during the post-HDBR Tilt + LBNP compared to pre-HDBR were correlated to OI, but not all of these abnormal responses were present in each of the NF subjects. Abnormal responses were more frequent in Con and Nut than in Ex-Lb subjects. (1) HDBR did not affect the cardiac, arterial and venous responses to the orthostatic test to the same extent in each subject. (2) Exercise within LBNP partially preserved the cardiovascular response to Tilt, while Nutrition supplementation had no efficacy. (3) Cerebral/femoral flow ratio and aortic flow were the parameters most closely related to OI. (4) Reduction in aortic flow was not the major hemodynamic change preceding syncope.     

Body volume changes during simulated microgravity: Auditory changes,segmental fluid redistribution,and regional hemodynamics

Space adaptation syndrome (SAS), manifested by cephalad fluid shifts, spacial disorientation, nausea, and vomiting, is of varied expression and uncertain etiology. One theory is that fluid shift to the upper body alters the function of the vestibular apparatus to create an entity similar to Meniere's disease. Since clinical vestibular dysfunction syndromes are mirored by altered cochlear function, this experiment was undertaken to study the relation between fluid redistribution and the auditory effects of initial antiorthostatic bed rest. Manual and bone audiometry, impedance tympanometry, and brain-stem evoked potentials were used to monitor auditory changes prior to, during, and following short term exposure to−6° head down tilt. Impedance plethysmography was performed to assess the segmental and intracranial fluid redistribution and hemodynamic changes during short-term head down tilt simulated microgravity. Even though significant cephalad fluid shift produced marked intracranial congestion and the subjects exhibited SAS symptoms, no clinically significant changes in the auditory system could be detected.     

Marked exacerbation of orthostatic intolerance after long- vs. short-duration spaceflight in veteran astronauts.

OBJECTIVE: The incidence of postflight orthostatic intolerance after short-duration spaceflight is about 20%. However, the incidence after long-duration spaceflight was unknown. The purpose of this study was to test the hypothesis that orthostatic intolerance is more severe after long-duration than after short-duration flight. METHODS: We performed tilt tests on six astronauts before and after long-duration (129-190 days) spaceflights and compared these data with data obtained during stand tests before and after previous short-duration missions. RESULTS: Five of the six astronauts studied became presyncopal during tilt testing after long-duration flights. Only one had become presyncopal during stand testing after short-duration flights. We also compared the long-duration flight tilt test data to tilt test data from 20 different astronauts who flew on the short-duration Shuttle missions that delivered and recovered the astronauts to and from the Mir Space Station. Five of these 20 astronauts became presyncopal on landing day. Heart rate responses to tilt were no different between astronauts on long-duration flights and astronauts on short-duration flights, but long-duration subjects had lower stroke volumes and cardiac outputs than short-duration presyncopal subjects, suggesting a possible decrease in cardiac contractile function. One subject had subnormal norepinephrine release with upright posture after the long flight but not after the short flight. Plasma volume losses were not greater after long flights. CONCLUSION: Long-duration spaceflight markedly increases orthostatic intolerance, probably with multiple contributing factors.     

Does resistance exercise prevent body fluid changes after a 90-day bed rest?

Although various exercise regimens are commonly used as countermeasures to reduce the cardiovascular deconditioning induced by microgravity, the underlying mechanisms are not well understood. In this study we aimed to test whether lower limb resistance exercise with flywheel technology can prevent the fluid homeostasis alterations induced by 90-day head-down tilt bed-rest (HDT), and thus improve orthostatic tolerance. Total body water (TBW, measured by isotope dilution) and plasma volume (PV, calculated from the haemoglobin and the haematocrit) were measured in a control group (Co, n=9) and a countermeasure group (CM, n=9). Simultaneously, plasma atrial natriuretic peptide (ANP), renin (AR), and aldosterone (Aldo), as well as urinary anti-diuretic hormone (ADH), were measured. Orthostatic tolerance was evaluated with a 10 min +80° tilt-test the first day of recovery. After HDT, both groups showed a comparable decrease in orthostatic tolerance [8.2 (0.9) min, Co; 8.0 (0.7) min, CM], PV [–4.7 (1.8)%, Co; –6.2 (2.5)%, CM, P<0.05] and TBW [–6.3 (5.4)%, Co; –3.7 (2.1)%, CM, P<0.05]. AR [97.4 (22.0)%, Co; 117.3 (26.4)%, CM] and Aldo [111.3 (58.4)%, Co; 100.6 (52.0)%, CM] increased significantly in both groups but the countermeasures produced no noticeable effects [data are expressed as mean (SE)]. The drop in ANP was also similar in both groups [–42.0 (15.2)%, Co; –51.1 (27.7)% for the CM]. Surprisingly, urinary ADH declined similarly in both groups during the basal data control period [–25.3 (5.2)%, Co; –26.1 (9.6)%, CM) and was sustained at this level during the 90-day HDT. These results show that, under the conditions described, the flywheel exercise device failed to improve characteristic manifestations of cardiovascular deconditioning and suggest that more frequent and powerful exercise, associated with another device (e.g. LBNP) might be a better countermeasure.     

On the edema-preventing effect of the calf muscle pump

Summary During motionless standing an increased hydrostatic pressure leads to increased transcapillary fluid filtration into the interstitial space of the tissues of the lower extremities. The resulting changes in calf volume were measured using a mercury-in-silastic strain gauge. Following a change in body posture from lying to standing or sitting a two-stage change in calf volume was observed. A fast initial filling of the capacitance vessels was followed by a slow but continuous increase in calf volume during motionless standing and sitting with the legs dependent passively. The mean rates of this slow increase were about 0.17%·min⁻¹ during standing and 0.12%·min⁻¹ during sitting, respectively. During cycle ergometer exercise the plethysmographic recordings were highly influenced by movement artifacts. These artifacts, however, were removed from the recordings by low-pass filtering. As a result the slow volume changes, i.e. changes of the extravascular fluid were selected from the recorded signal. Contrary to the increases during standing and sitting the calf volumes of all 30 subjects decreased during cycle ergometer exercise. The mean decrease during 18 min of cycling (2–20 min) was −1.6% at 50 W work load and −1.9% at 100 W, respectively. This difference was statistically significant (p≤0.01). The factors which may counteract the development of an interstitial edema, even during quiet standing and sitting, are discussed in detail. During cycling, however, three factors are most likely to contribute to the observed reduction in calf volume: (1) The decrease in venous pressure, which in turn reduces the effective filtration pressure. (2) An increased lymph flow, which removes fluid and osmotically active colloid proteins from the interstitial space. (3) An increase in muscle tissue pressure, which counteracts the intravascular pressure during the muscle contraction thus playing an important role as an edema-preventing factor, which has not been considered to date.     

Cardiovascular deconditioning in microgravity: some possible countermeasures

Microgravity is an extreme environment inducing relevant adaptive changes in the human body, especially after prolonged periods of exposure. Since the early sixties, numerous studies on the effects of microgravity, during manned Space flights, have produced an increasing amount of information concerning its physiological effects, globally defined "deconditioning". Microgravity deconditioning of the cardiovascular system (CVD) is briefly reviewed. It consists of: (1) a decrease of circulating blood and interstitial fluid volumes, (2) a decrease of arterial blood diastolic pressure, (3) a decrease of ventricular stroke volume, (4) a decrease of the estimated left ventricular mass and (5) resetting of the carotid baroreceptors. The negative effects of microgravity deconditioning manifest themselves mostly upon the reentry to Earth. They consist mainly of: (1) dizziness, (2) increased heart rate and heart palpitations, (3) an inability to assume the standing position (orthostatic intolerance), (4) pre-syncopal feelings due to postural stress and (5) reduced exercise capacity. To avoid these drawbacks several countermeasures have been proposed; they will be briefly mentioned with emphasis on the "Twin Bikes System" (TBS). This consists of two coupled bicycles operated by astronauts and counter-rotating along the inner wall of a cylindrical Space module, thus generating a centrifugal force vector, mimicking gravity.     

Cardiovascular control and stabilization via inclination and mobilization during bed rest

Cardiovascular deconditioning has long been recognized as a characteristic of the physiological adaptation to long-term bed rest in patients. The process is thought to contribute to orthostatic intolerance and enhance secondary complications in a significant way. Mobilization is a cost-effective and simple method to maintain the cardiovascular parameters (i.e., blood pressure, heart rate) stable, counter orthostatic intolerance and reduce the risk of secondary problems in patients during long-term immobilization. The aim of this project is to control the cardiovascular parameters such as heart rate and blood pressure of bed rest patients via automated leg mobilization and body tilting. In a first step, a nonlinear model predictive control strategy was designed and evaluated on five healthy subjects and 11 bed rest patients. In a next step, a clinically feasible study was conducted on two patients. The mean values differed on average less than 1 bpm from the predetermined heart rate and less than 2.5 mmHg from the desired blood pressure values. These results of the feasibility study are promising, although heterogeneous disease etiologies and individual medication strongly influence the mechanically induced reactions. The long-term goal is an automation of the control of physiological signals and the mobilization of bed rest patients in an early phase of the rehabilitation process. Therefore, this new approach could help to strengthen the cardiovascular system and prevent secondary health problems arising from long-term bed rest.     

An indifference point for electrical impedance in humans

Regional electrical impedance was used over eight sections of the human body (two thoracic; one abdominal; two thigh; two around the knee; and one lower leg) to determine the volume indifference point during passive head-up tilt in eight subjects. Head-up tilt was performed in 10± increments from 0± to 60± over 6 min. Electrical impedance increased over the thorax in proportion to the head-up tilt angle, while abdominal impedance did not change significantly, and over the thigh and the lower leg it decreased with increasing head-up tilt angle. No change in electrical impedance was noted just above the knee, and electrical impedance just below the knee decreased only marginally. Results demonstrate minimal fluid accumulation around the knee during head-up tilt. Furthermore, in humans the electrical impedance and therefore probably the volume indifference point is positioned between the umbilicus and crista iliaca.     

Body fluid distribution in man in space and effect of lower body negative pressure treatment

Summary The lack of hydrostatic forces in space eventually produces a fluid deficit within the circulatory system. This deficit may alter the circulatory regulation patterns. The aim of the present study was to determine how much of this fluid deficit is attributable to interstitial fluid losses and to determine the effects of lower body negative pressure (LBNP) treatment on fluid distribution. The body fluid distribution of one subject was assessed before, during, and after weightlessness using two electrical impedance methods: (a) standard quadripole impedance for the segments of upper torso, lower torso, thigh, and calf and (b) an electrical impedance tomography technique (applied potential tomography) for a thigh cross-section. To assess the content of interstitial free fluid a thigh cuff overlying the electrodes for applied potential tomography was inflated to suprasystolic values to ascertain how much fluid can be squeezed out of blood vessels and tissue of skin and muscle. After the first thigh cuff maneuver (CUFF I) the subject performed a cardiovascular stress test with LBNP to mimic the gravity-induced blood shift to the lower part of the body. Then the compression maneuver was repeated (CUFF II). (a) This experimental sequence demonstrated a reduction in interstitial fluid in weightlessness of roughly 40% at the thigh. (b) The CUFF I and LBNP experiment demonstrated a reduced ability to cope with blood pooling in microgravity. (c) The CUFF II experiment suggests that LBNP in microgravity can refill the interstitial spaces and counteract the associated cardiovascular deterioration. The impedance measurements provided estimates of the contribution of different body sections to the observed body weight loss of more than 6 kg. The chest contributed nothing of significance, the lower torso more than 0.5 1, and both calves roughly 1.5 1. The thigh segments of both legs contributed between 1.51 and 2.01 with an interstitial free fluid reduction in muscle and skin by 40%.Abbreviations APT applied potential tomography - AU arbitrary units - LBNP lower-body negative pressure     

No effect of venoconstrictive thigh cuffs on orthostatic hypotension induced by head‐down bed rest

Orthostatic intolerance (OI) is the most serious symptom of cardiovascular deconditioning induced by head‐down bed rest or weightlessness. Wearing venoconstrictive thigh cuffs is an empirical countermeasure used by Russian cosmonauts to limit the shift of fluid from the lower part of the body to the cardio‐cephalic region. Our aim was to determine whether or not thigh cuffs help to prevent orthostatic hypotension induced by head‐down bed rest. We studied the effect of thigh cuffs on eight healthy men. The cuffs were worn during the day for 7 days of head‐down bed rest. We measured: orthostatic tolerance (stand tests and lower body negative pressure tests), plasma volume (Evans blue dilution), autonomic influences (plasma noradrenaline) and baroreflex sensitivity (spontaneous baroreflex slope). Thigh cuffs limited the loss of plasma volume (thigh cuffs: ?201 ± 37 mL vs. control: ?345 ± 42 mL, P < 0.05), the degree of tachycardia and reduction in the spontaneous baroreflex sensitivity induced by head‐down bed rest. However, the impact of thigh cuffs was not sufficient to prevent OI (thigh cuffs: 7.0 min of standing time vs. control: 7.1 min). Decrease in absolute plasma volume and in baroreflex sensitivity are known to be important factors in the aetiology of OI induced by head‐down bed rest. However, dealing with these factors, using thigh cuffs for example, is not sufficient to prevent OI. Other factors such as venous compliance, microcirculatory changes, peripheral arterial vasoconstriction and vestibular afferents must also be considered.     

Simulated Stand Tests and Centrifuge Training to Prevent Orthostatic Intolerance on Earth,Moon, and Mars

One proposed method to overcome postflight orthostatic intolerance is for astronauts to undergo inflight centrifugation. Cardiovascular responses were compared between centrifuge and gravitational conditions using a seven-compartment cardiovascular model. Vascular resistance, heart rate, and stroke volume values were adopted from literature, while compartmental volumes and compliances were derived from impedance plethysmography of subjects (n = 8) riding on a centrifuge. Three different models were developed to represent the typical male subject who completed a 10-min postflight stand test (“male finisher”), “non-finishing male” and “female” (all non-finishers). A sensitivity analysis found that both cardiac output and arterial pressure were most sensitive to total blood volume. Simulated stand tests showed that female astronauts were more susceptible to orthostatic intolerance due to lower initial blood pressure and higher pressure threshold for presyncope. Rates of blood volume loss by capillary filtration were found to be equivalent in female and male non-finishers, but four times smaller in male finishers. For equivalent times to presyncope during centrifugation as those during constant gravity, lower G forces at the level of the heart were required. Centrifuge G levels to match other cardiovascular parameters varied depending on the parameter, centrifuge arm length, and the gravity level being matched.     

Transcapillary fluid movement in human calf after drinking hypertonic saline

1. Transcapillary absorption of interstitial fluid was demonstrated with a pressure plethysmograph applied to the human calf after the ingestion of 200 ml. hypertonic (5.1%) saline. Capillary absorption began within 15 min after ingestion and lasted for about 2 hr. The maximum rate of absorption (0.019 ml./min. 100 ml. tissue) was attained 30-75 min after ingestion.2. The total amount of fluid absorbed into capillary blood vessels in the calf was 1.11 ml./100 ml. tissue. The amount of fluid thus absorbed in the whole body was estimated to be 677 ml.3. The capillary filtration coefficient (CFC) of the calf was also measured by the pressure plethysmograph. This was 0.0038 ml./min. mm Hg. 100 ml. tissue.4. The peak value of capillary absorption pressure was 5.2 mm Hg.5. The total osmotic pressure of the plasma rose by 12.6 m-osmole/kg H(2)O after ingestion. This rise was accompanied by transcapillary fluid absorption.6. The plasma protein concentration and packed cell volume were almost unchanged by ingestion, indicating that the plasma volume was unaltered.7. It was estimated that the net shift of fluid between intracellular and interstitial compartments during the period of transcapillary fluid absorption was very small.8. It is concluded that the volume of fluid moving from plasma into intestinal lumen is the same as that flowing from interstitial fluid into plasma, and that the transcapillary absorption is caused by a difference in osmotic pressure between the plasma and the interstitial fluid.     

Cardiovascular response during head-up tilt in chronic fatigue syndrome.

This study examined the cardiovascular response to orthostatic challenge, and incidence and mechanisms of neurally mediated hypotension in chronic fatigue syndrome (CFS) during a head-up tilt test. Stoke volume was obtained by a thoracic impedance cardiograph, and continuous heart rate and blood pressure were recorded during a 45-min 70 degrees head-up tilt test. Thirty-nine CFS patients and 31 healthy physically inactive control subjects were studied. A positive tilt, i.e. a drop in systolic blood pressure of > 25 mmHg, no concurrent increase in heart rate and/or development of presyncopal symptoms, was seen in 11 CFS patients and 12 control subjects (P > 0.05). During baseline and the first 5 min of head-up tilt, CFS patients had higher heart rate and smaller pulsatile-systolic area than control subjects (P < 0.05). Among subjects who completed the test, those with CFS had higher heart rate and smaller stroke volume (P < 0.05) than corresponding control subjects. When comparing those who had a positive test outcome in each group, CFS patients had higher heart rates and lower pulse pressure and pulsatile-systolic areas during the last 4 min before being returned to supine (P < 0.05). These data show that there are baseline differences in the cardiovascular profiles of CFS patients when compared with control subjects and that this profile is maintained during head-up tilt. However, the frequency of positive tilts and the haemodynamic adjustments made to this orthostatic challenge are not different between groups.     

No effect of venoconstrictive thigh cuffs on orthostatic hypotension induced by head-down bed rest

Orthostatic intolerance (OI) is the most serious symptom of cardiovascular deconditioning induced by head-down bed rest or weightlessness. Wearing venoconstrictive thigh cuffs is an empirical countermeasure used by Russian cosmonauts to limit the shift of fluid from the lower part of the body to the cardio-cephalic region. Our aim was to determine whether or not thigh cuffs help to prevent orthostatic hypotension induced by head-down bed rest. We studied the effect of thigh cuffs on eight healthy men. The cuffs were worn during the day for 7 days of head-down bed rest. We measured: orthostatic tolerance (stand tests and lower body negative pressure tests), plasma volume (Evans blue dilution), autonomic influences (plasma noradrenaline) and baroreflex sensitivity (spontaneous baroreflex slope). Thigh cuffs limited the loss of plasma volume (thigh cuffs: -201 +/- 37 mL vs. control: -345 +/- 42 mL, P < 0.05), the degree of tachycardia and reduction in the spontaneous baroreflex sensitivity induced by head-down bed rest. However, the impact of thigh cuffs was not sufficient to prevent OI (thigh cuffs: 7.0 min of standing time vs. control: 7.1 min). Decrease in absolute plasma volume and in baroreflex sensitivity are known to be important factors in the aetiology of OI induced by head-down bed rest. However, dealing with these factors, using thigh cuffs for example, is not sufficient to prevent OI. Other factors such as venous compliance, microcirculatory changes, peripheral arterial vasoconstriction and vestibular afferents must also be considered.