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Plasma endothelin-1 and -3 in cirrhosis: relationship with systemic hemodynamics, renal function and neurohumoral systems.

BACKGROUND/AIMS: The postural change from upright to supine is a physiological maneuvre which increases central blood volume. This model was used to investigate the effects of changes in effective volemia on plasma endothelin-1 and -3 concentrations in cirrhosis. METHODS: Plasma endothelin concentrations, measured by radio-immunoassay, were determined in 20 patients with cirrhosis, 10 of whom has ascites, and nine healthy control subjects, in the upright posture and 30, 60 and 120 min after the assumption of the supine position. RESULTS: In the upright posture, endothelin-1 was 8.9 +/- 0.4 pg/ml and endothelin-3 3.7 +/- 0.6 (mean +/- SEM) pg/ml in control subjects. Endothelin-1 was increased only in patients with ascites (12.7 +/- 1.4 pg/ml, p < 0.05; patients without ascites: 9.7 +/- 0.7 pg/ml), while endothelin-3 was elevated in both patients with and without ascites (8.0 +/- 1.5 pg/ml, p < 0.01; 5.9 +/- 0.5 pg/ml, p = 0.01, respectively). In the supine position, no significant changes in endothelin-1 or -3 occurred either in patients with ascites or in controls throughout the observation period, while a reduction in endothelin-3 was found in compensated patients after 30 and 60 min. In patients, we found negative correlations between endothelin-3, but not endothelin-1, and mean arterial pressure, both in upright (r = -0.59; p < 0.01) and supine (r = -0.56; p = 0.01) positions, atrial natriuretic factor (r = 0.50; p < 0.05) and plasma renin activity (r = 0.67; p = 0.001) in the supine position alone. In patients with ascites, endothelin-1 was inversely correlated with both glomerular filtration rate (upright: r = -0.62; p = 0.06; supine: r = -0.71, p < 0.05) and renal sodium excretion (upright: r = -0.82; p < 0.01; supine: r = -0.88; p < 0.001). CONCLUSIONS: Plasma endothelin-1 and -3 were increased in cirrhosis with ascites, while, in pre-ascitic cirrhosis, only endothelin-3 was increased in the upright posture. Although increased endothelin-3 was associated with features suggesting a reduced effective volemia, it is likely that other mechanisms than hypovolemia were mainly responsible for high plasma endothelin levels. Increased endothelin production may play a role in circulatory and renal function abnormalities of advanced cirrhosis.

Adult↗

Optimal position for a cervical collar incision: a prospective study.

BACKGROUND: The descriptions of the optimal method for placing a cervical collar incision for thyroidectomy or parathyroidectomy are varied. It has been our impression that a collar incision marked in the neutral upright neck, migrates superiorly relative to the sternal notch when the patient is placed in the supine position. The aim of this study was to investigate the validity of this impression and to assess whether this is influenced by patient factors and/or pathology. METHODS: Fifty patients undergoing either thyroid or parathyroid surgery had a planned incision marked 1 finger-breadth (17 mm) above the sternal notch when sitting in the upright position. When placed in the supine position, with neck extended, the distance from the sternal notch to the marked incision was remeasured. Patient variables such as body mass index, height, weight and neck circumference were documented prospectively and data were recorded on operative details and tumour pathology. RESULTS: The collar incision marked in the neutral upright neck, migrated on average 21 mm superiorly once the patient was placed supine with the neck extended (P=0. 0001 ).The extent of migration was independent of all patient factors, type of operation and thyroid or parathyroid pathology. CONCLUSIONS: Migration of a proposed cervical collar incision does occur. An inappropriately placed incision may lead to excessive scarring if it is too low, or unusual prominence if it is too high. We believe a good position for marking such an incision is 1 fingerbreadth above the sternal notch with the patient in a neutral, upright position.

Cicatrix↗

Effects of "priming" exercise on pulmonary O2 uptake and muscle deoxygenation kinetics during heavy-intensity cycle exercise in the supine and upright positions.

We hypothesized that the performance of prior heavy exercise would speed the phase 2 oxygen consumption (VO2) kinetics during subsequent heavy exercise in the supine position (where perfusion pressure might limit muscle O2 supply) but not in the upright position. Eight healthy men (mean +/- SD age 24 +/- 7 yr; body mass 75.0 +/- 5.8 kg) completed a double-step test protocol involving two bouts of 6 min of heavy cycle exercise, separated by a 10-min recovery period, on two occasions in each of the upright and supine positions. Pulmonary O2 uptake was measured breath by breath and muscle oxygenation was assessed using near-infrared spectroscopy (NIRS). The NIRS data indicated that the performance of prior exercise resulted in hyperemia in both body positions. In the upright position, prior exercise had no significant effect on the time constant tau of the VO2 response in phase 2 (bout 1: 29 +/- 10 vs. bout 2: 28 +/- 4 s; P = 0.91) but reduced the amplitude of the VO2 slow component (bout 1: 0.45 +/- 0.16 vs. bout 2: 0.22 +/- 0.14 l/min; P = 0.006) during subsequent heavy exercise. In contrast, in the supine position, prior exercise resulted in a significant reduction in the phase 2 tau (bout 1: 38 +/- 18 vs. bout 2: 24 +/- 9 s; P = 0.03) but did not alter the amplitude of the VO2 slow component (bout 1: 0.40 +/- 0.29 vs. bout 2: 0.41 +/- 0.20 l/min; P = 0.86). These results suggest that the performance of prior heavy exercise enables a speeding of phase 2 VO2 kinetics during heavy exercise in the supine position, presumably by negating an O2 delivery limitation that was extant in the control condition, but not during upright exercise, where muscle O2 supply was probably not limiting.

Adaptation, Physiological↗

2000 Volvo Award winner in biomechanical studies: Monitoring in vivo implant loads with a telemeterized internal spinal fixation device.

STUDY DESIGN: Implant loads were measured in 10 patients using telemeterized internal spinal fixation devices. OBJECTIVE: To determine the postoperative temporal course of implant loads. SUMMARY OF BACKGROUND DATA: Little information exists regarding the temporal course of loads on internal spinal fixation devices. METHODS: The telemeterized internal spinal fixator allows the measurement of three force components and three moments acting in the fixator. Implant loads were determined in up to 20 measuring sessions for different activities, including walking, standing, sitting, lying in the supine position, and lifting an extended leg while in the supine position. RESULTS: Implant loads often increased shortly after anterior interbody fusion was performed. Several patients retained the same high level even after fusion had taken place. This explains the reason why screw breakage sometimes occurs more than half a year after implantation. The time of fusion could not be pinpointed from the loading curves. CONCLUSIONS: The results show that fixators may be highly loaded even after fusion has occurred. A flexion bending moment acts on the implant even with the body in a relaxed lying position. This means that already shortly after the anterior procedure, the shape of the spine is not neutral and unloaded, but slightly deformed, which loads the fixators. Pedicle screw breakage more than half a year after insertion does not prove that anterior interbody fusion has not occurred.

Adult↗

Nocturnal low back pain in pregnancy: polysomnographic correlates.

Thirteen women in late stages of pregnancy underwent a polysomnographic study. Eight women (61%) complained of mild nocturnal back pain or back discomfort. Five women (39%) did not complain of nocturnal back pain. The two groups did not differ in total bed time, total sleep time, sleep latency, and wake after sleep onset (WASO). A significant decrease in rapid eye movement (REM) sleep and an increase in stage 2 were observed in the pain group. The same group had a statistically significant decrease in the basal O2 saturation level. The pain group also spent a longer time sleeping in the supine position. We hypothesize that a prolonged stay in the supine position leads to obstruction of the vena cava. In the presence of inadequate collateral circulation, increased pressure and venostasis in combination with a decrease in basal oxygen saturation may lead to hypoxemia, compromise the metabolic supply of the neural structures, and result in pain. It appears, therefore, that the vascular system plays an important role in the pathogenesis of pain. The role played by the disturbed sleep architecture in the production of pain remains to be established. It is possible that the changes observed in sleep architecture result from pain rather than contribute to pain production.

Adult↗

Effect of heliox breathing on dynamic hyperinflation in COPD patients.

BACKGROUND: and objective: Patients with COPD exhibit increased inspiratory work and dyspnea due to dynamic hyperinflation caused by expiratory flow limitation. Helium-oxygen mixtures (ie, heliox) have been used in treating these patients on the assumption that, by lowering airway resistance, they might be beneficial. METHODS: In 22 patients with COPD, the presence of expiratory flow limitation was assessed with patients in the sitting and supine positions using the negative expiratory pressure technique, and the effects of heliox (80% He, 20% O2) on breathing pattern, expiratory flow limitation, and dynamic hyperinflation, evaluated from the change in inspiratory capacity (IC), were measured at rest and were compared with those due to inhaled salbutamol. RESULTS: During air breathing, 13 patients experienced flow limitation while in the sitting position and 18 experienced flow limitation while in the supine position. Neither heliox nor salbutamol therapy changed the breathing pattern in any of the patients, regardless of posture and the presence or absence of expiratory flow limitation. However, in both positions IC increased significantly in most flow-limited patients after bronchodilator administration, but not after heliox administration. CONCLUSIONS: Since heliox had no effect on dynamic hyperinflation, the use of this gas mixture, which is costly and cumbersome, does not appear to be beneficial in stable patients with COPD breathing at rest.

Aged↗

[Echocardiographic parameters in normal pregnant women].

The authors report the results of a transverse prospective study of 80 normal women, divided into 4 groups of 20: control group, 1st trimester of pregnancy, 2nd trimester of pregnancy, 3rd trimester of pregnancy. These groups were comparable in terms of age, height and haemoglobin level. No significant difference was observed in terms of obstetric profile between the various groups of women. The results did not reveal any difference concerning the morphology of cardiac structures, the parameters of left ventricular diastolic filling and the frequency of valvular regurgitation. On the other hand, diameters and cavity volumes, left ventricular mass, left ventricular ejection fraction, and maximal antegrade aortic and pulmonary blood flow rates were higher during pregnancy; these increases were less marked when the measurements were performed in the dorsal supine position compared to those observed in the left lateral supine position.

Adult↗

Significant reduction of the large-vessel blood volume by food intake during hemodialysis.

Postprandial hypotension during hemodialysis is a serious problem. The reduction of the blood volume (BV) by ultrafiltration and the redistribution of the blood from the large vessels to the splanchnic organs are regarded to be the principle mechanisms of postprandial hypotension during hemodialysis. The hematocrit (Ht) of the large vessels is expected to increase by ultrafiltration and also by peripheral shift of the blood, because Ht of the peripheral vessels is much less than Ht of the large vessels. To analyze the effects of food intake during hemodialysis on BV of the large vessels quantitatively, we monitored Ht of the arteriovenous shunt blood continuously in the patients treated with hemodialysis regularly and estimated BV using the following equation, i.e., BV/initial BV = initial Ht/Ht. The rate of ultrafiltration was kept constant during the study. The reduction rate of BV was expressed as percentage of the initial BV per hour (delta BV). Ultrafiltration rate was expressed as percentage of the dry weight per hour (delta BV), delta BV was 3.24 +/- 0.57%/h (mean +/- SE) before the meal and increased to 13.99 +/- 0.91%/h almost instantaneously when the meal started in the supine position. The minimum value of BV was less than that estimated from the ultrafiltration rate by 2.65 +/- 0.26% of the initial BV. The effects of food intake disappeared in 43 +/- 3 minutes. When the meal was taken in the sitting position, delta BV was 28.21 +/- 2.14%/h, and the minimum value of BV was less than that estimated from the ultrafiltration rate by 4.69 +/- 0.70% of the initial BV. We conclude that food intake during hemodialysis decreases BV of the large vessels transiently but significantly. The effects of food intake on BV were more severe when the meal was taken in sitting position than those when the meal was taken in supine position.

Adult↗

Arterial oxygen saturation in infants at risk of sudden death: influence of sleeping position.

To study the possible influence of sleeping position on arterial oxygen saturation, measured by pulse oximetry (SpO2), 7-h overnight recordings of breathing movements and ECG were performed in 43 infants (median age 2.4 months, range 0.2-11 months) at increased risk of sudden infant death syndrome (SIDS). Infants were randomly allocated to start sleeping either in their usual sleeping position or in the opposite position. After 3.5 h, all infants were gently turned over. Thus, each infant served as their own control. Recordings were analysed for sleep time, baseline SpO2 (only during regular breathing), and the number and duration of desaturations (a decrease in SpO2 to < or = 80%). In the prone position, a significantly higher proportion of time was spent asleep (median 79% versus 70%; p < 0.05). Median baseline SpO2 was 98.8% (91.7-100%) in the prone and 99.0% (92.0-100%) in the supine position (ns). A total of 191 desaturations were found in 29 recordings; 96 in the prone and 95 in the supine position (ns). One infant subsequently died of SIDS while sleeping in the prone position. He had a relatively high number of desaturations (n = 12) which all occurred in the prone position. These results confirm earlier studies which could not find a significant influence of sleeping position on baseline oxygenation. The occurrence of desaturations in the prone position only in the infant who subsequently died requires further investigation.

Electrocardiography↗

Cyclotorsion: a possible cause of residual astigmatism in refractive surgery.

PURPOSE: To determine whether cyclotorsion occurs when a subject changes from binocular to monocular fixation and to assess positionally induced cyclotorsion. SETTING: Clinics of the Rotterdam Eye Hospital, Rotterdam, The Netherlands. METHODS: The axis of astigmatism was measured with the Nidek handheld keratometer in 15 normal subjects under monocular and binocular fixation and in seated and supine positions. The limits of agreement for the repeatability of measurements with the Nidek keratometer were used to identify subjects with statistically significant cyclotorsion. RESULTS: Two subjects (13%) showed statistically significant excyclotorsion when changing from binocular to monocular fixation in a seated position. In a supine position, 3 subjects (20%) showed excyclotorsion when the fixation changed. Body position itself had no influence on ocular torsion. CONCLUSIONS: Significant cyclotorsion may occur under monocular viewing conditions. If monocular photorefractive keratectomy procedures are based on binocular keratometry readings, an undercorrection of myopic astigmatism may result. Individuals at risk should be identified before refractive keratectomy is performed.

Astigmatism↗

Analysis of downbeat nystagmus. Otolithic vs semicircular canal influences.

The relative strengths of vertical canal and otolithic factors influencing downbeat nystagmus (DBN) were investigated in a patient whose nystagmus was of maximum intensity with the head in the upright position and abolished with the head in the supine position. The vestibuloocular reflex (VOR) was assessed by oscillating the patient about both the supine and upright positions. During oscillation about the supine position both the upward and downward VORs had equal gains in the dark (0.6) and unity gain in the light. In contrast, during oscillation about the upright, the upward VOR became hyperactive with a gain of 1.8 in the dark and 1.2 in the light, whereas the downward VOR became hypoactive with a maximum gain of 0.86 in the light. This degree of asymmetry of the VOR is greater than would be expected from a summation of spontaneous nystagmus with normal canal reflexes. We concluded that the DBN arose from an asymmetry of vertical canal function, which became manifest when the otoliths were tilted with respect to gravity. Contrasting findings are presented in a patient whose DBN was insensitive to tilt. It would seem that other cases of DBN lie on a continuum between these extreme examples.

Adult↗

Active standing and passive tilting similarly reduce the slope of spontaneous baroreflex in healthy subjects.

Non-invasive assessment of the sensitivity of cardiac baroreflex was performed by recording each RR-interval and each blood pressure cycle (Finapres). In sequences of at least three cardiac cycles in which systolic blood pressure and RR-interval had changed in the same direction, the slope of linear regression of RR duration as a function of the change in systolic arterial pressure was taken for estimating the sensitivity of the spontaneous cardiac baroreflex. This technique was used in healthy humans to examine how a postural change from supine to upright by either active standing up or 60 degrees head-up tilting modified the sensitivity of the spontaneous baroreflex. We observed that the slope of the spontaneous baroreflex averaged 14.6 +/- 2 ms.mm Hg-1 during rest in the supine position, and decreased to 7.8 +/- 1.2 ms.mm Hg-1 (p < 0.05) after active standing, while the number of sequences was significantly increased in the upright as compared to the supine position. Head-up tilting by 60 degrees led to values similar to those following active standing. The adjustment of baroreflex slope to either postural change occurred in a few seconds, so that posture-characteristic values were obtained from five-minute records. We conclude that non-invasive recording of spontaneous sequences of related changes in blood pressure and RR-interval during several minutes provides reproducible values of the slope of cardiac baroreflex in the supine and upright position. This easy and reliable determination of the sensitivity of the cardiac baroreflex might prove to be useful when assessment of baroreflex function is needed.

Adult↗

Modulation of esophageal peristalsis by alterations of body position. Effect of bolus viscosity.

Previous studies have demonstrated that nonviscous liquids traverse the esophagus more rapidly with the subject in the upright rather than the supine position. Conversely, similar studies have shown that viscous liquids traverse the esophagus at similar rates for both upright and supine positions. Our purpose was to define the motor correlates of these differing responses. Six normal volunteers were studied with an infused catheter system incorporating a Dent sleeve for monitoring lower esophageal sphincter pressure. The subjects were given a series of swallows of a water and a viscous (52 centipoise) bolus in both the supine and upright positions. In the upright position, the water bolus caused an increased velocity of propagation in the proximal esophageal segment that was associated with a shortening of lower esophageal sphincter relaxation time and reductions in amplitude and duration of contraction. No significant changes in the peristaltic wave were noted with the viscous bolus during alterations of body position. We conclude that the more rapid transit of a nonviscous water bolus through the esophagus in the upright position is reflected in specific alterations of esophageal peristaltic parameters. The possible mechanisms for these differing responses are discussed.

Adult↗

Vertical instability in spondylolisthesis: a traction radiographic assessment technique and the principle of management.

STUDY DESIGN: Lateral radiographs of the lumbar spine were taken of 40 patients with lumbar spondylolisthesis. These radiographs were taken in the neutral, flexion, and extension positions for both erect and recumbent postures, and also in the prone and supine positions with traction applied via a traction table. OBJECTIVES: To define and demonstrate the presence of "vertical instability" in spondylolisthesis, and to determine the most useful radiographic views for clinical purposes and analysis of the surgical principle. SUMMARY OF BACKGROUND DATA: Lateral radiographs of patients in flexion and extension are widely used to obtain quantitative and qualitative data on lumbar spondylolisthesis. Changes in lumbar disc height and segmental translation in a group of patients with spondylolisthesis have been demonstrated with the addition of traction and compression. METHODS: Lateral and flexion extension radiographs of the lumbosacral spine in 37 patients with spondylolisthesis taken in standing and recumbent positions and under pelvic traction in the prone or supine positions were suitable for analysis. The changes in disc area, intervertebral kyphotic slip angle, and amount of anteroposterior shift (olisthesis) were measured from the radiographs using a computer digitizer. The disc area was normalized against the area of the superior vertebra, and the amount of anteroposterior shift was normalized against the anteroposterior width of the superior vertebra. Inter- and intraobserver error was found to be negligible, and results were analyzed by paired t test. RESULTS: Maximum slip angle, maximum olisthesis, and minimum normalized disc area were found with the subject under erect flexion. Conversely, prone traction and recumbent extension produced minimum slip angle, whereas the lowest anteroposterior shifts were seen with the subject under prone and supine traction. Prone traction also resulted in a significantly larger normalized disc area than any other posture. The change in kyphotic slip angle between erect flexion and prone traction is correlated with the change in normalized olisthesis and disc area. CONCLUSIONS: Erect flexion and prone traction radiographs represent the extremes of subluxation and reduction of the olisthesis, respectively, and the change in olisthesis seen between these extremes is correlated with the change in disc area and the intervertebral slip angle. Vertical laxity of the affected functional spinal unit resulting from disc degeneration produces laxity in the ligaments and disc anulus, allowing olisthetic motion. Restoration of disc height in turn restores tension to the soft tissues around the disc and results in a spontaneous reduction of the subluxation. Restoration and maintenance of disc height with a spacer or interbody fusion therefore is recommended as a goal in the treatment of spondylolisthesis. When spondylolytic spondylolisthesis involves a posterior column deficiency, additional reconstruction of this column with posterior instrumentation is recommended. Application of the traction radiographic technique in planning for spondylolisthesis reduction is discussed along with the technique of stabilization.

Adolescent↗

Additive effect of nitric oxide inhalation on the oxygenation benefit of the prone position in the adult respiratory distress syndrome.

BACKGROUND: The response to inhaled nitric oxide and prone positioning was investigated in 47 patients with adult respiratory distress syndrome to test the hypothesis that inhalation of nitric oxide when in the prone position would result in additive improvement in oxygenation. METHODS: The authors prospectively studied patients of both genders who were 15 to 75 yr old and had adult respiratory distress syndrome confirmed by computed tomography (lung injury score, 3.1+/-1). RESULTS: Compared with baseline values in the supine position (T1), inhalation of 10 ppm nitric oxide for 1 h (T2) decreased the mean pulmonary artery pressure from 33+/-9 mmHg to 28+/-6 mmHg (P < 0.05; T2 vs. T1) and increased the ratio of the partial pressure of oxygen in arterial blood (PaO2) to inspired oxygen concentration (FiO2) from 115 (median first quartile [Q1] 97, median third quartile [Q3] 137) to 148 (Q1 132, Q3 196) (P < 0.05; T2 vs. T1). Cessation of nitric oxide brought the values back to baseline (T3). Two hours of prone positioning (T4) significantly increased the PaO2:FiO2 ratio (T4 vs. T3). However, after an additional hour of nitric oxide inhalation in the prone position (T5), a significant decrease of the venous admixture (from 33+/-6% to 25+/-6%; P < 0.05) and an increase of the PaO2:FiO2 ratio (from 165 [Q1 129, Q3 216] to 199 [Q1 178, Q3 316] [P < 0.05; T5 vs. T4]) were observed. CONCLUSIONS: In patients with isolated severe adult respiratory distress syndrome, inhalation of nitric oxide in the prone position significantly improved oxygenation compared with nitric oxide inhalation in the supine position or in the prone position without nitric oxide. The combination of the prone position with nitric oxide inhalation in the treatment of severe adult respiratory distress syndrome should be considered.

Adolescent↗

The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome.

Prone positioning improves gas exchange in some patients with adult respiratory distress syndrome (ARDS), but the effects of repeated, long-term prone positioning (20 h duration) have never been evaluated systemically. We therefore investigated 20 patients with ARDS after multiple trauma (Injury Severity Score [ISS] 27.3 +/- 10, ARDS score 2.84 +/- 0.42). Patients who fulfilled the entry criteria (bilateral diffuse infiltrates, severe hypoxemia, pulmonary artery occlusion pressure [PAOP] < 18 mm Hg, and PaO2/fraction of inspired oxygen [FIO2] < 200 mm Hg at inverse ratio ventilation with positive end-expiratory pressure [PEEP] > 8 mm Hg for more than 24 h) were turned to the prone position at noon and were turned back to the supine position at 8:00 AM on the next day. Thus only two turns per day were necessary, and the risk of disconnecting airways or medical lines was minimized. Prone positioning was repeated for another 20 h if the patients fulfilled the entry criteria. Except for FIO2, the ventilator settings remained unchanged during the study period. All patients were sedated and, if needed paralyzed to minimize patient discomfort. One hour before and after each position change, ventilator settings and pulmonary and systemic hemodynamics were recorded and blood was obtained for blood gas analysis. Derived cardiopulmonary and ventilatory variables were calculated using standard formulas. Overall mortality was 10%. Oxygenation variables improved significantly each time the patients were placed prone. Immediately after the first turn from the supine to the prone position the following changes were observed: PaO2 increased from 97 +/- 4 to 152 +/- 15 mm Hg, intrapulmonary shunt (Qva/Qt) decreased from 30.3 +/- 2.3 to 25.5 +/- 1.8, and the alveolar-arterial oxygen difference decreased from 424 +/- 24 to 339 +/- 25 mm Hg. All these changes were statistically significant. Most of these improvements were lost when the patients were turned supine, but could be reproduced when prone positioning was repeated after a short period (4 h) in the supine position. Short periods in the supine position were necessary to allow for nursing care, medical evaluation, and interventions such as placement of central lines. No position-dependent changes of systemic hemodynamic variables were observed. We conclude that, in trauma patients with ARDS undergoing long-term positioning treatment, lung function improves significantly during prone position compared to short phases of conventional supine position during which the beneficial effects are partly lost.

Adult↗

Regional blood flow in the calf and plasma endothelin during prolonged orthostasis in humans.

This study tested the hypothesis that circulating plasma levels of the vasoconstrictor endothelin increase during prolonged orthostasis in association with changes in both calf regional blood flow, systemic arterial blood pressure and heart rate, and that the 133Xenon wash-out method can be used for prolonged registration of skeletal muscle blood flow. The simultaneous effects of prolonged orthostasis on plasma endothelin, calf skeletal muscle and subcutaneous blood flow, heart rate and arterial blood pressure were investigated in 13 healthy subjects before, during and after 30 min of 50 degree head-up tilt. Blood flow rate was measured by the local 133Xenon wash-out method in the supine position and during 50 degree head-up tilt. The method was evaluated for skeletal muscle for prolonged observation in the supine position in five subjects and compared with blood flow rates measured with plethysmography. Plasma endothelin was unchanged during head-up tilt, despite a maximal reduction in skeletal muscle blood flow rate of 47% (p<0.001) and subcutaneous blood flow rate of 80% (p<0.01) and a maximal increase in heart rate of 15% (p<0.001) and diastolic (12%, p<0.01) blood pressure. The skeletal muscle wash-out curves for 133Xenon were monoexponential from 30 min after injection and at least during the next hour and correlated with total limb blood flow rate assessed simultaneously with plethysmography (r=0.76, p<0.0001). Circulating endothelin does not appear to be in the first line of regulation of calf microcirculation, systemic arterial blood pressure or heart rate during prolonged orthostasis. The 133Xenon wash-out method can be used for prolonged measurement of skeletal muscle blood flow.

Adult↗