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Dwain L Eckberg

Publications and source records attributed to Dwain L Eckberg.

15 recordsLinked to original sources
PubMed2006

Human cerebral autoregulation before, during and after spaceflight.

Exposure to microgravity alters the distribution of body fluids and the degree of distension of cranial blood vessels, and these changes in turn may provoke structural remodelling and altered cerebral autoregulation. Impaired cerebral autoregulation has been documented following weightlessness simulated by head-down bed rest in humans, and is proposed as a mechanism responsible for postspaceflight orthostatic intolerance. In this study, we tested the hypothesis that spaceflight impairs cerebral autoregulation. We studied six astronauts approximately 72 and 23 days before, after 1 and 2 weeks in space (n = 4), on landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat-by-beat changes of photoplethysmographic mean arterial pressure and transcranial Doppler middle cerebral artery blood flow velocity were measured during 5 min of spontaneous breathing, 30 mmHg lower body suction to simulate standing in space, and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral autoregulation was quantified by analysis of the transfer function between spontaneous changes of mean arterial pressure and cerebral artery blood flow velocity, in the very low- (0.02-0.07 Hz), low- (0.07-0.20 Hz) and high-frequency (0.20-0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not change significantly from preflight values during or after spaceflight. Reductions of cerebral blood flow velocity during lower body suction were significant before spaceflight (P < 0.05, repeated measures ANOVA), but not during or after spaceflight. Absolute and percentage reductions of mean (+/- s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after than before spaceflight (absolute, -4 +/- 3 cm s(-1) after versus -14 +/- 3 cm s(-1) before, P = 0.001; and percentage, -8.0 +/- 4.8% after versus -24.8 +/- 4.4% before, P < 0.05), consistent with improved rather than impaired cerebral blood flow regulation. Low-frequency gain decreased significantly (P < 0.05) by 26, 23 and 27% after 1 and 2 weeks in space and on landing day, respectively, compared with preflight values, which is also consistent with improved autoregulation. We conclude that human cerebral autoregulation is preserved, and possibly even improved, by short-duration spaceflight.

Adaptation, Physiological↗
PubMed2005

Human vagal baroreflex sensitivity fluctuates widely and rhythmically at very low frequencies.

Arterial pressure fluctuates rhythmically in healthy supine resting humans, who, from all outward appearances, are in a 'steady-state'. Others have asked, If baroreflex mechanisms are functioning normally, how can arterial pressure be so variable? We reanalysed data from nine healthy young adult men and women and tested the hypotheses that during brief periods of observation, human baroreflex sensitivity fluctuates widely and rhythmically. We estimated vagal baroreflex sensitivity with systolic pressure and R-R interval cross-spectra measured over 15 s segments, moved by 2 s steps through 20-min periods of frequency- and tidal volume-controlled breathing. We studied each subject at the same time on three separate days, with fixed protocols that included two physiological states, supine and passive 40 deg upright tilt, before and after beta-adrenergic, cholinergic, and angiotensin converting enzyme blockade. Minimum, mean and maximum (+/-s.d.) supine control baroreflex sensitivities averaged 5 +/- 3, 18 +/- 6, and 55 +/- 22 ms mmHg(-1). In most subjects, moderate ongoing fluctuations of baroreflex sensitivity were punctuated by brief major peaks, yielding frequency distributions that were skewed positively. Fast Fourier transforms indicated that baroreflex sensitivity fluctuations (expressed as percentages of total power) concentrated more in very low, 0.003-0.04 Hz, than ultra low, 0.0-0.003 Hz, frequencies (77 +/- 7 versus 11 +/- 8%, P < or = 0.001, rank sum test). Autoregressive centre frequencies averaged 0.012 +/- 0.003 Hz. The periodicity of very low frequency baroreflex sensitivity fluctuations was not influenced significantly by upright tilt, or by variations of autonomic drive or angiotensin activity. Our analysis indicates that during ostensibly 'steady-state' conditions, human vagal baroreflex sensitivity fluctuates in a major way, at very low frequencies.

Adrenergic beta-Agonists↗
PubMed2003

The human respiratory gate.

Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

Autonomic Nervous System↗
PubMed2003

A prognostic index to predict long-term mortality in patients with mild to moderate chronic heart failure stabilised on angiotensin converting enzyme inhibitors.

BACKGROUND: Mortality in patients with mild to moderate chronic heart failure remains high. At present there is no easy way of identifying patients within this population at increased risk of death in the medium to long term. AIMS: To develop a prognostic index to identify outpatients with mild to moderate chronic heart failure at increased risk of death. METHODS AND RESULTS: Five hundred and fifty-three outpatients mean (S.D.) age 63(+/-10) years with symptoms of chronic heart failure (mean New York Heart Association functional class, 2.3(+/-0.5)), were recruited between December 1993 and April 1995. By April 2000, 201 patients had died. Using data from non-invasive measurements of cardiac size, electrical and autonomic function, renal function and plasma biochemistry we identified eight independent predictors of mortality (all P<0.01). To develop a prognostic index, predictors were dichotomised by group median and awarded 0 or 1 point accordingly. Serum sodium </=140 mmol/l (1 point), creatinine >/=111 micromol/l (1 point), cardiothoracic ratio >/=0.52 (1 point), SDNN </=112 ms (1 point), maximum corrected QT interval >/=487 ms (1 point), QRS dispersion>/=42.7 ms (1 point), the presence of non-sustained ventricular tachycardia (1 point) and voltage criteria for left ventricular hypertrophy on 12-lead ECG (1 point). We calculated risk scores for patients by adding the points of each independent risk factor. In the low-risk group (0-3 points) mortality at 5 years was 20% and in the high-risk group (4-8 points) 53%. The area under the receiver-operator characteristic curve using dichotomised variables was 0.74 and for continuous model 0.78. CONCLUSIONS: Our prognostic index which uses eight non-invasive measurements and a straightforward additive points system, has good discrimination and stratifies outpatients with chronic heart failure into high and low risk. This index may be useful in clinical care and risk stratification.

Adolescent↗
PubMed2003

Spontaneous 'baroreflex sequences' occur as deterministic functions of breathing phase.

Parallel increases or decreases of systolic pressures and R-R intervals occur spontaneously in healthy resting humans, and are thought to be expressions of vagal baroreflex physiology. We studied ten healthy supine young adults, and tested the null hypothesis that spontaneous baroreflex sequences are distributed uniformly throughout the breathing cycle. We recorded the electrocardiogram, photoplethysmographic arterial pressure, respiration (pneumobelt), and peroneal nerve muscle sympathetic activity in supine subjects who breathed spontaneously, or held their breaths in inspiration after 2 min of hyperventilation with 100% oxygen. We analysed pairs of three or more increasing or decreasing systolic pressures and R-R intervals with linear regression, and related the gain and timing of the onset of such sequences to the phase of respiration, and to preceding muscle sympathetic nerve activity. We found that baroreflex sequences occur erratically, at a frequency about one-third that of breathing. However, when baroreflex sequences do occur, the timing of their onset is dictated by the phase of respiration. Parallel increases of systolic pressures and R-R intervals ('up' sequences) begin just before and after the beginning of expiration, and parallel decreases of systolic pressures and R-R intervals ('down' sequences) begin during late expiration and inspiration. Average gains of up and down baroreflex sequences triggered by muscle sympathetic bursts are comparable during breathing and apnoea. However, the latencies between sympathetic bursts and baroreflex sequences are less during breathing than during apnoea. We propose that parallel systolic pressure--R-R interval sequences are expressions of arterial baroreflex physiology, and that the nearly fixed timing of such sequences within breaths reflects simply respiratory gating of muscle sympathetic bursts.

Adult↗
PubMed2003

Cardiac size, autonomic function, and 5-year follow-up of chronic heart failure patients with severe prolongation of ventricular activation.

BACKGROUND: Chronic heart failure is characterized by left ventricular dilation and abnormalities of cardiac autonomic function. Up to 20% of patients with chronic heart failure have QRS prolongation, which can lead to asynchronous left ventricular contraction. We tested the hypotheses that in patients with chronic heart failure, QRS > 150 ms is a risk factor for additional abnormalities of ventricular morphology, heart rate variability, and increased mortality. METHODS AND RESULTS: In 184 patients with left ventricular ejection fraction < 35%, QRS duration was > 150 ms in 53, and </= 150 ms in 131. We evaluated patients with baseline chest radiographs, echocardiograms, and Holter recordings. Patients with QRS duration above and below 150 ms were similar in age, sex, functional class, renal function, serum sodium, and ejection fraction. In patients with QRS > 150 ms, left ventricular end-diastolic and end-systolic diameters were greater than patients with QRS duration </=150 ms (P <.01). Patients with QRS > 150 ms had less low frequency R-R interval spectral power (P <.04). At 5 years 60% of patients with QRS > 150 ms had died compared with 35% of patients with QRS </=150 ms (P <.001). This increase in mortality was predominantly the result of an increase in progressive heart failure. CONCLUSIONS: Chronic heart failure patients with QRS duration > 150 ms have exaggerated disturbance of cardiac autonomic function, and left ventricular remodeling and significantly higher mortality than patients with QRS duration </= 150 ms.

Autonomic Nervous System↗
PubMed2002

Predicting death due to progressive heart failure in patients with mild-to-moderate chronic heart failure.

OBJECTIVES: The aim of this study was to explore the value of noninvasive predictors of death/mode of death in ambulant outpatients with chronic heart failure (HF). BACKGROUND: Mortality in chronic HF remains high, with a significant number of patients dying of progressive disease. Identification of these patients is important. METHODS: We recruited 553 ambulant outpatients age 63 +/- 10 years with symptoms of chronic HF (New York Heart Association functional class, 2.3 +/- 0.5) and objective evidence of left ventricular dysfunction (ejection fraction <45%, cardiothoracic ratio >0.55, or pulmonary edema on chest radiograph). After 2,365 patient-years of follow-up, 201 patients had died, with 76 events due to progressive HF. RESULTS: Independent predictors of all-cause mortality assessed with the Cox proportional hazards model were as follows: a low standard deviation of all normal-to-normal RR intervals (SDNN); lower serum sodium and higher creatinine levels; higher cardiothoracic ratio; nonsustained ventricular tachycardia; higher left ventricular end-systolic diameter; left ventricular hypertrophy; and increasing age. Independent predictors of death specific to progressive HF were SDNN, serum sodium and creatinine levels. The hazard ratio of progressive HF death for a 10% decrease in SDNN was 1.06 (95% confidence interval [CI], 1.01 to 1.12); for a 2 mmol/l decrease in serum sodium, 1.22 (95% CI, 1.08 to 1.38); and for a 10 micromol/l increase in serum creatinine, 1.14 (95% CI, 1.09 to 1.19) (all p < 0.01). CONCLUSIONS: In ambulant outpatients with chronic HF, low serum sodium and SDNN and high serum creatinine identify patients at increased risk of death due to progressive HF.

Adolescent↗
PubMed2002

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.

Adult↗
PubMed2002

Cerebral blood flow velocity declines before arterial pressure in patients with orthostatic vasovagal presyncope.

OBJECTIVES: We studied hemodynamic changes leading to orthostatic vasovagal presyncope to determine whether changes of cerebral artery blood flow velocity precede or follow reductions of arterial pressure. BACKGROUND: Some evidence suggests that disordered cerebral autoregulation contributes to the occurrence of orthostatic vasovagal syncope. We studied cerebral hemodynamics with transcranial Doppler recordings, and we closely examined the temporal sequence of changes of cerebral artery blood flow velocity and systemic arterial pressure in 15 patients who did or did not faint during passive 70 degrees head-up tilt. METHODS: We recorded photoplethysmographic arterial pressure, RR intervals (electrocardiogram) and middle cerebral artery blood flow velocities (mean, total, mean/RR interval; Gosling's pulsatility index; and cerebrovascular resistance [mean cerebral velocity/mean arterial pressure, MAP]). RESULTS: Eight men developed presyncope, and six men and one woman did not. Presyncopal patients reported light-headedness, diaphoresis, or a sensation of fatigue 155 s (range: 25 to 414 s) before any cerebral or systemic hemodynamic change. Average cerebral blood flow velocity (CBFV) changes (defined by an iterative linear regression algorithm) began 67 s (range: 9 to 198 s) before reductions of MAP. Cerebral and systemic hemodynamic measurements remained constant in nonsyncopal patients. CONCLUSIONS: Presyncopal symptoms and CBFV changes precede arterial pressure reductions in patients with orthostatic vasovagal syncope. Therefore, changes of cerebrovascular regulation may contribute to the occurrence of vasovagal reactions.

Blood Flow Velocity↗
PubMed2002

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.

Adult↗
PubMed2002

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.

Adult↗
PubMed2002

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.

Adult↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMedDate not supplied

Heart rate variability biofeedback increases baroreflex gain and peak expiratory flow.

OBJECTIVE: We evaluated heart rate variability biofeedback as a method for increasing vagal baroreflex gain and improving pulmonary function among 54 healthy adults. METHODS: We compared 10 sessions of biofeedback training with an uninstructed control. Cognitive and physiological effects were measured in four of the sessions. RESULTS: We found acute increases in low-frequency and total spectrum heart rate variability, and in vagal baroreflex gain, correlated with slow breathing during biofeedback periods. Increased baseline baroreflex gain also occurred across sessions in the biofeedback group, independent of respiratory changes, and peak expiratory flow increased in this group, independently of cardiovascular changes. Biofeedback was accompanied by fewer adverse relaxation side effects than the control condition. CONCLUSIONS: Heart rate variability biofeedback had strong long-term influences on resting baroreflex gain and pulmonary function. It should be examined as a method for treating cardiovascular and pulmonary diseases. Also, this study demonstrates neuroplasticity of the baroreflex.

Adult↗