Engineering topics

Diedrich, Andre

Publications and source records attributed to Diedrich, Andre.

11 records

NASA NTRS2007

Effects of Daily Centrifugation on Segmental Fluid Distribution in Bed-rested Subjects

The effect of daily centrifugation on segmental fluid distribution have been studied during 21 days of 6 degree head down bedrest. One group (N=7) underwent no countermeasure while the other (N=8) received a daily, one hour, dose (2.5 gz at the foot, decreasing to 1.0 gz at the heart) of artificial gravity (AG) training on the Johnson Space Center short radius centrifuge. Fluid shifts of thoracic(VTO), abdominal (VAB), thigh (VTH), and calf (VCA) regions were measured by the tetrapolar segmental body impedance technique. Untrained subjects reduced their total volume from 18.9 plus or minus 0.5L to 17.9 plus or minus 0.9L (MN plus or minus SE, P less than 0.05) while trained subjects maintained their total volume. In untrained, control, subjects after bed rest, there was a trend toward reduced volume in all segments, with significant reductions in thigh and calf (fig, P less than 0.05). Trained subjects maintained volume in all segments. Our data indicate that artificial gravity treatment counteracts bed rest-induced hypovolemia.

Diedrich, Andre↗

NASA NTRS2003

The Human Sympathetic Nervous System Response to Spaceflight

The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

Ertl, Andrew C.↗

NASA NTRS2002

Cardiovascular and sympathetic neural responses to handgrip and cold pressor stimuli in humans before, during and after spaceflight

Astronauts returning to Earth have reduced orthostatic tolerance and exercise capacity. Alterations in autonomic nervous system and neuromuscular function after spaceflight might contribute to this problem. In this study, we tested the hypothesis that exposure to microgravity impairs autonomic neural control of sympathetic outflow in response to peripheral afferent stimulation produced by handgrip and a cold pressor test in humans. We studied five astronauts approximately 72 and 23 days before, and on landing day after the 16 day Neurolab (STS-90) space shuttle mission, and four of the astronauts during flight (day 12 or 13). Heart rate, arterial pressure and peroneal muscle sympathetic nerve activity (MSNA) were recorded before and during static handgrip sustained to fatigue at 40 % of maximum voluntary contraction, followed by 2 min of circulatory arrest pre-, in- and post-flight. The cold pressor test was applied only before (five astronauts) and during flight (day 12 or 13, four astronauts). Mean (+/- S.E.M.) baseline heart rates and arterial pressures were similar among pre-, in- and post-flight measurements. At the same relative fatiguing force, the peak systolic pressure and mean arterial pressure during static handgrip were not different before, during and after spaceflight. The peak diastolic pressure tended to be higher post- than pre-flight (112 +/- 6 vs. 99 +/- 5 mmHg, P = 0.088). Contraction-induced rises in heart rate were similar pre-, in- and post-flight. MSNA was higher post-flight in all subjects before static handgrip (26 +/- 4 post- vs. 15 +/- 4 bursts min(-1) pre-flight, P = 0.017). Contraction-evoked peak MSNA responses were not different before, during, and after spaceflight (41 +/- 4, 38 +/- 5 and 46 +/- 6 bursts min(-1), all P > 0.05). MSNA during post-handgrip circulatory arrest was higher post- than pre- or in-flight (41 +/- 1 vs. 33 +/- 3 and 30 +/- 5 bursts min(-1), P = 0.038 and 0.036). Similarly, responses of MSNA and blood pressure to the cold pressor test were well maintained in-flight. We conclude that modulation of muscle sympathetic neural outflow by muscle metaboreceptors and skin nociceptors is preserved during short duration spaceflight.

NASA Discipline Neuroscience↗

NASA NTRS2002

The nature of the autonomic dysfunction in multiple system atrophy

The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

NASA Discipline Regulatory Physiology↗

NASA NTRS2002

Water drinking as a treatment for orthostatic syndromes

PURPOSE: Water drinking increases blood pressure in a substantial proportion of patients who have severe orthostatic hypotension due to autonomic failure. We tested the hypothesis that water drinking can be used as a practical treatment for patients with orthostatic and postprandial hypotension, as well as those with orthostatic tachycardia. SUBJECTS AND METHODS: We studied the effect of drinking water on seated and standing blood pressure and heart rate in 11 patients who had severe orthostatic hypotension due to autonomic failure and in 9 patients who had orthostatic tachycardia due to idiopathic orthostatic intolerance. We also tested the effect of water drinking on postprandial hypotension in 7 patients who had autonomic failure. Patients drank 480 mL of tap water at room temperature in less than 5 minutes. RESULTS: In patients with autonomic failure, mean (+/- SD) blood pressure after 1 minute of standing was 83 +/- 6/53 +/- 3.4 mm Hg at baseline, which increased to 114 +/- 30/66 +/- 18 mm Hg (P <0.01) 35 minutes after drinking. After a meal, blood pressure decreased by 43 +/- 36/20 +/- 13 mm Hg without water drinking, compared with 22 +/- 10/12 +/- 5 mm Hg with drinking (P <0.001). In patients with idiopathic orthostatic intolerance, water drinking attenuated orthostatic tachycardia (123 +/- 23 beats per minute) at baseline to 108 +/- 21 beats per minute after water drinking ( P <0.001). CONCLUSION: Water drinking elicits a rapid pressor response in patients with autonomic failure and can be used to treat orthostatic and postprandial hypotension. Water drinking moderately reduces orthostatic tachycardia in patients with idiopathic orthostatic intolerance. Thus, water drinking may serve as an adjunctive treatment in patients with impaired orthostatic tolerance.

Non-NASA Center↗

NASA NTRS2002

Baroreflex buffering and susceptibility to vasoactive drugs

BACKGROUND: The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known. METHODS AND RESULTS: We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects. We used phenylephrine sensitivity during ganglionic blockade as a measure of baroreflex buffering. Phenylephrine (25 microg) increased systolic blood pressure 6+/-1.6 mm Hg in control subjects, 6+/-1.1 mm Hg in orthostatic intolerance patients, 18+/-3.9 mm Hg in patients with essential hypertension, 31+/-3.4 mm Hg in patients with monogenic hypertension, and 25+/-3.4 mm Hg in patients with multiple system atrophy. Similar differences in sensitivities between groups were observed with nitroprusside. The sensitivity to vasoactive drugs was highly correlated with baroreflex buffering function and to a lesser degree with baroreflex control of heart rate. In control subjects, sensitivities to nitroprusside and phenylephrine infusions were correlated with baroreflex heart rate control and sympathetic nerve traffic. CONCLUSIONS: Our findings are consistent with an important effect of baroreflex blood pressure buffering on the sensitivity to vasoactive drugs. They suggest that even moderate changes in baroreflex function may have a substantial effect on the sensitivity to vasoactive medications.

NASA Discipline Regulatory Physiology↗

NASA NTRS2002

Selective norepinephrine reuptake inhibition as a human model of orthostatic intolerance

BACKGROUND: Observations in patients with functional mutations of the norepinephrine transporter (NET) gene suggest that impaired norepinephrine uptake may contribute to idiopathic orthostatic intolerance. METHODS AND RESULTS: We studied the effect of the selective NET blocker reboxetine and placebo in a randomized, double-blind, crossover fashion on cardiovascular responses to cold pressor testing, handgrip testing, and a graded head-up tilt test (HUT) in 18 healthy subjects. In a subset, we determined isoproterenol and phenylephrine sensitivities. Subjects ingested 8 mg reboxetine or placebo 12 hours and 1 hour before testing. In the supine position, heart rate was 65+/-2 bpm with placebo and 71+/-3 bpm with reboxetine. At 75 degrees HUT, heart rate was 84+/-3 and 119+/-4 bpm with placebo and with reboxetine (P<0.0001). Mean arterial pressure was 85+/-2 with placebo and 91+/-2 mm Hg with reboxetine while supine (P<0.01) and 88+/-2 mm Hg and 90+/-3 mm Hg at 75 degrees HUT. Blood pressure responses to cold pressor and handgrip testing were attenuated with reboxetine. Reboxetine increased the sensitivity to the chronotropic effect of isoproterenol and the pressor effect of phenylephrine. Vasovagal reactions occurred in 9 subjects on placebo and in 1 subject on reboxetine. CONCLUSIONS: Selective NET blockade creates a phenotype that resembles idiopathic orthostatic intolerance. This observation supports the hypothesis that disordered norepinephrine uptake mechanisms can contribute to human cardiovascular disease. Our study also suggests that NET inhibition might be useful in preventing vasovagal reactions.

Non-NASA Center↗

NASA NTRS2002

Increased sympathetic activation in idiopathic orthostatic intolerance: role of systemic adrenoreceptor sensitivity

Idiopathic orthostatic intolerance (OI) is characterized by adrenergic symptoms with standing. Changes in central sympathetic tone or in adrenoreceptor sensitivity could contribute to this syndrome. In OI patients and control subjects, we determined heart rate (HR) and systolic blood pressure (SBP) changes after incremental bolus doses of isoproterenol and phenylephrine before and during ganglionic blockade with trimethaphan. SBP decreased by 17+/-1.6 mm Hg in patients and 3.9+/-3.8 mm Hg in control subjects (P<0.01) with trimethaphan. Patients with a larger decrease (28+/-3.8 mm Hg, n=7) in SBP with trimethaphan had greater supine SBP and supine and upright plasma norepinephrine levels than did patients with a lesser decrease (3.0+/-3.0 mm Hg, n=7) in SBP. Supine and orthostatic HRs were similar for the groups. The majority of patients had a normal HR response to isoproterenol before and during ganglionic blockade. Phenylephrine increased SBP similarly in patients and control subjects before and during blockade. Sympathetic support is increased in a subgroup of OI patients. Hyperadrenergic and nonhyperadrenergic subgroups have similar degrees of orthostatic tachycardia. Our findings suggest that the hyperadrenergic features of OI cannot be completely explained by systemic hypersensitivity of postsynaptic alpha(1)- and beta-adrenoreceptors but rather originates in enhanced sympathetic activation.

Non-NASA Center↗

NASA NTRS2002

Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

Non-NASA Center↗

NASA NTRS2002

Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space

Astronauts returning from space have reduced red blood cell masses, hypovolaemia and orthostatic intolerance, marked by greater cardio-acceleration during standing than before spaceflight, and in some, orthostatic hypotension and presyncope. Adaptation of the sympathetic nervous system occurring during spaceflight may be responsible for these postflight alterations. We tested the hypotheses that exposure to microgravity reduces sympathetic neural outflow and impairs sympathetic neural responses to orthostatic stress. We measured heart rate, photoplethysmographic finger arterial pressure, peroneal nerve muscle sympathetic activity and plasma noradrenaline spillover and clearance, in male astronauts before, during (flight day 12 or 13) and after the 16 day Neurolab space shuttle mission. Measurements were made during supine rest and orthostatic stress, as simulated on Earth and in space by 7 min periods of 15 and 30 mmHg lower body suction. Mean (+/- S.E.M.) heart rates before lower body suction were similar pre-flight and in flight. Heart rate responses to -30 mmHg were greater in flight (from 56 +/- 4 to 72 +/- 4 beats min(-1)) than pre-flight (from 56 +/- 4 at rest to 62 +/- 4 beats min(-1), P < 0.05). Noradrenaline spillover and clearance were increased from pre-flight levels during baseline periods and during lower body suction, both in flight (n = 3) and on post-flight days 1 or 2 (n = 5, P < 0.05). In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33 %) in the same three subjects in whom noradrenaline spillover and clearance were increased. The sympathetic response to 30 mmHg lower body suction was at pre-flight levels or higher in each subject (35 pre-flight vs. 40 bursts min(-1) in flight). No astronaut experienced presyncope during lower body suction in space (or during upright tilt following the Neurolab mission). We conclude that in space, baseline sympathetic neural outflow is increased moderately and sympathetic responses to lower body suction are exaggerated. Therefore, notwithstanding hypovolaemia, astronauts respond normally to simulated orthostatic stress and are able to maintain their arterial pressures at normal levels.

STS-90 Shuttle Project↗

NASA NTRS2002

Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre

When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38-44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre-flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445% during 30 mmHg straining on earth and 792% in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain.

Non-NASA Center↗