D L Eckberg

Lancaster University, Lancaster, England, United Kingdom

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Publications (143)698.96 Total impact

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    ABSTRACT: We varied the timing of respiration as a means to modulate and better understand otherwise hidden human central neural and cardiovascular mechanisms. Time-frequency methods (wavelet transform, wavelet phase coherence, and directional coupling) were applied to analyze these time-varying signals. We found that respiration causally modulates both sympathetic (weakly) and vagal motoneuron (strongly) oscillations over a wide frequency range - one that extends well below the frequency of actual breaths. Breathing frequency does not affect phase coherence between diastolic pressure and muscle sympathetic oscillations, but it augments phase coherence between systolic pressure and R-R interval oscillations over a limited portion of the usual breathing frequency range.
    2014 8th Conference of the European Study Group on Cardiovascular Oscillations (ESGCO); 05/2014
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    ABSTRACT: We experimentally altered the timing of respiratory motoneuron activity, as a means to modulate and better understand otherwise hidden human central neural and hemodynamic oscillatory mechanisms. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations, and muscle sympathetic nerve activity in 13 healthy supine young men, who gradually increased or decreased their breathing frequencies between 0.05 and 0.25 Hz over 9 min periods. We analyzed results with traditional time- and frequency-domain methods, and also with time-frequency methods: wavelet transform, wavelet phase coherence, and directional coupling. We determined statistical significance and identified frequency boundaries by comparing measurements with randomly-generated surrogates. Our results support several major conclusions. First, respiration causally modulates both sympathetic (weakly) and vagal motoneuron (strongly) oscillations, over a wide frequency range - one that extends well below the frequency of actual breaths. Second, breathing frequency broadly modulates vagal baroreflex gain, with peak gains registered in the low-frequency range. Third, breathing frequency does not influence median levels of sympathetic or vagal activity over time. Fourth, phase relations between arterial pressure and sympathetic and vagal motoneurons are unaffected by breathing, and therefore likely secondary to intrinsic responsiveness of these motoneurons to other synaptic inputs. Finally, breathing frequency does not affect phase coherence between diastolic pressure and muscle sympathetic oscillations, but augments phase coherence between systolic pressure and R-R interval oscillations, over a limited portion of the usual breathing frequency range. These results refine understanding of autonomic oscillatory processes and those physiological mechanisms known as the human respiratory gate.
    Journal of Applied Physiology 10/2013; · 3.48 Impact Factor
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    ABSTRACT: To determine if physiological, rhythmic fluctuations of vagal baroreflex gain persist during exercise, post-exercise ischaemia, and recovery. We studied responses of six supine healthy men and one woman to a stereotyped protocol comprising rest, handgrip exercise at 40 % maximum capacity to exhaustion, post-exercise forearm ischaemia, and recovery. We measured electrocardiographic R-R intervals, photoplethysmographic finger arterial pressures, and peroneal nerve muscle sympathetic activity. We derived vagal baroreflex gains from a sliding (25 s window moved by 2 s steps) systolic pressure - R-R interval transfer function at 0.04 - 0.15 Hz. Vagal baroreflex gain oscillated at low, nearly constant frequencies throughout the protocol (at ~ 0.06 Hz - a period of about 18 s); however, during exercise, most oscillations were at low gain levels, and during ischaemia and recovery, most oscillations were at high gain levels. Vagal baroreflex rhythms are not abolished by exercise, and they are not overwhelmed after exercise during ischaemia and recovery. This article is protected by copyright. All rights reserved.
    Acta Physiologica 06/2013; · 4.38 Impact Factor
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    ABSTRACT: Since it is likely that in healthy human subjects, baroreflex mechanisms operate continuously, independent of experimental interventions, we asked the question, In what ways might study of unprovoked, very infrequent muscle sympathetic bursts inform baroreflex physiology? We closely examined arterial pressure and R-R interval responses of 11 supine healthy young subjects to arterial pressure ramps triggered by large isolated muscle sympathetic bursts. We triggered data collection sweeps on the beginnings of sympathetic bursts, and plotted changes of arterial pressure (finger volume clamp or intraarterial) and R-R intervals occurring before, as well as after the sympathetic triggers. We estimated baroreflex gain from regression of R-R intervals on systolic pressures after sympathetic bursts, and from the transfer function between cross-spectra of systolic pressure and R-R intervals at low frequencies. Isolated muscle sympathetic bursts were preceded by arterial pressure reductions. Baroreflex gain, calculated with linear regression of R-R intervals on systolic pressures after bursts, was virtually identical to baroreflex gain, calculated with the cross-spectral modulus [mean and (range): 24 (7 to 43) vs. 24 (8 to 45) ms/mmHg], and highly significant, according to linear regression (r(2) = 0.91, P = 0.001). Our results indicate that 1) since infrequent human muscle sympathetic bursts are almost deterministically preceded by arterial pressure reductions, their occurrence likely reflects simple baroreflex physiology, and 2) the noninvasive low-frequency modulus reliably reproduces gains derived from R-R interval responses to arterial pressure ramps triggered by infrequent muscle sympathetic bursts.
    Journal of Applied Physiology 11/2012; · 3.48 Impact Factor
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    ABSTRACT: Frequency-domain analyses of simultaneously recorded skin and muscle sympathetic nerve activities may yield unique information on otherwise obscure central processes governing human neural outflows. We used wavelet transform and wavelet phase coherence methods to analyse integrated skin and muscle sympathetic nerve activities and haemodynamic fluctuations, recorded from nine healthy supine young men. We tested two null hypotheses: (1) that human skin and muscle sympathetic nerve activities oscillate congruently; and (2) that whole-body heating affects these neural outflows and their haemodynamic consequences in similar ways. Measurements included peroneal nerve skin and tibial nerve muscle sympathetic activities; the electrocardiogram; finger photoplethysmographic arterial pressure; respiration (controlled at 0.25 Hz, and registered with a nasal thermistor); and skin temperature, sweating, and laser-Doppler skin blood flow. We made recordings at ∼27°C, for ∼20 min, and then during room temperature increases to ∼38°C, over 35 min. We analysed data with a wavelet transform, using the Morlet mother wavelet and wavelet phase coherence, to determine the frequencies and coherences of oscillations over time. At 27°C, skin and muscle nerve activities oscillated coherently, at ever-changing frequencies between 0.01 and the cardiac frequency (∼1 Hz). Heating significantly augmented oscillations of skin sympathetic nerve activity and skin blood flow, arterial pressure, and R-R intervals, over a wide range of low frequencies, and modestly reduced coordination between skin and muscle sympathetic oscillations. These results suggest that human skin and muscle sympathetic motoneurones are similarly entrained by external influences, including those of arterial baroreceptors, respiration, and other less well-defined brainstem oscillators. Our study provides strong support for the existence of multiple, time-varying central sympathetic neural oscillators in human subjects.
    The Journal of Physiology 11/2011; 590(Pt 2):363-75. · 4.38 Impact Factor
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    ABSTRACT: Although astronauts' cardiovascular function is normal while they are in space, many have altered haemodynamic responses to standing after they return to Earth, including inordinate tachycardia, orthostatic hypotension, and uncommonly, syncope. Simulated microgravity impairs vagal baroreceptor-cardiac reflex function and causes orthostatic hypotension. Actual microgravity, however, has been shown to either increase, or not change vagal baroreflex gain. In this study, we tested the null hypothesis that spaceflight does not impair human baroreflex mechanisms. We studied 11 American and two German astronauts before, during (flight days 2-8), and after two, 9- and 10-day space shuttle missions, with graded neck pressure and suction, to elicit sigmoid, vagally mediated carotid baroreflex R-R interval responses. Baseline systolic pressures tended to be higher in space than on Earth (P = 0.015, repeated measures analysis of variance), and baseline R-R intervals tended to be lower (P = 0.049). Baroreceptor-cardiac reflex relations were displaced downward on the R-R interval axis in space. The average range of R-R interval responses to neck pressure changes declined from preflight levels by 37% on flight day 8 (P = 0.051), maximum R-R intervals declined by 14% (P = 0.003), and vagal baroreflex gain by 9% (P = 0.009). These measures returned to preflight levels by 7-10 days after astronauts returned to Earth. This study documents significant increases of arterial pressure and impairment of vagal baroreflex function in space. These results and results published earlier indicate that microgravity exposure augments sympathetic, and diminishes vagal cardiovascular influences.
    The Journal of Physiology 02/2010; 588(Pt 7):1129-38. · 4.38 Impact Factor
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    ABSTRACT: Fractal frequency scaling of heart period variability is used as a concise index of overall cardiac control. However, no prior study has assessed within-individual reproducibility of fractal indices of heart period, or reported how the estimated indices respond to autonomic blockade. Therefore, we examined fractal properties of the heart period from ten young, healthy individuals during three separate experimental sessions under control (saline) conditions and twice under combined autonomic blockade (atenolol and atropine sulfate) conditions. Under each condition, R-R intervals were recorded with the subject in the supine and the 40 deg upright tilt positions during 20 min of controlled breathing in each position. We calculated the fractal scaling exponent using detrended fluctuation analysis and estimated confidence intervals of the scaling exponents for each R-R interval time series within each individual. In the control condition, upright tilt significantly increased the scaling exponents (from 0.73 +/- 0.11 (+/-S.D., session 1), 0.72 +/- 0.10 (session 2) and 0.75 +/- 0.13 (session 3) to 0.82 +/- 0.12, 0.82 +/- 0.11 and 0.84 +/- 0.10; Student's paired t-test, t = 2.79, P = 0.02; t = 2.80, P = 0.02; and t = 2.07, P = 0.07). However, neither the absolute scaling exponents nor their change in response to upright tilt were reproducible (Lin's concordance coefficient less than 0.9, P > 0.1 for all comparisons). Following autonomic blockade, the scaling exponents were significantly increased (supine: 1.08 +/- 0.13 and 1.08 +/- 0.14; tilt: 1.07 +/- 0.21 and 1.08 +/- 0.14) for both experimental sessions (two-way repeated-measures ANOVA; F(17,1) = 40.89, P < 0.001 and F(17,1) = 42.72, P < 0.001) regardless of position. However, within individuals, the scaling exponents failed to distinguish between control and blockade for half of the subjects in at least one experimental session. Thus, fractal scaling exponents are not reproducible within individuals and do not reliably reflect the autonomic mechanisms responsible for heart period variability. In fact, data from combined blockade suggest that physiological effects of autonomic outflow may mask intrinsic fractal behaviour of the sinoatrial node.
    The Journal of Physiology 07/2009; 587(Pt 15):3929-41. · 4.38 Impact Factor
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    ABSTRACT: A paradox regarding the classic power spectral analysis of heart rate variability (HRV) is whether the characteristic high- (HF) and low-frequency (LF) spectral peaks represent stochastic or chaotic phenomena. Resolution of this fundamental issue is key to unraveling the mechanisms of HRV, which is critical to its proper use as a noninvasive marker for cardiac mortality risk assessment and stratification in congestive heart failure (CHF) and other cardiac dysfunctions. However, conventional techniques of nonlinear time series analysis generally lack sufficient sensitivity, specificity and robustness to discriminate chaos from random noise, much less quantify the chaos level. Here, we apply a 'litmus test' for heartbeat chaos based on a novel noise titration assay which affords a robust, specific, time-resolved and quantitative measure of the relative chaos level. Noise titration of running short-segment Holter tachograms from healthy subjects revealed circadian-dependent (or sleep/wake-dependent) heartbeat chaos that was linked to the HF component (respiratory sinus arrhythmia). The relative 'HF chaos' levels were similar in young and elderly subjects despite proportional age-related decreases in HF and LF power. In contrast, the near-regular heartbeat in CHF patients was primarily nonchaotic except punctuated by undetected ectopic beats and other abnormal beats, causing transient chaos. Such profound circadian-, age- and CHF-dependent changes in the chaotic and spectral characteristics of HRV were accompanied by little changes in approximate entropy, a measure of signal irregularity. The salient chaotic signatures of HRV in these subject groups reveal distinct autonomic, cardiac, respiratory and circadian/sleep-wake mechanisms that distinguish health and aging from CHF.
    PLoS ONE 02/2009; 4(2):e4323. · 3.53 Impact Factor
  • Dwain L Eckberg
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    ABSTRACT: Many cardiovascular models involve prediction of changes that occur when a subject is perturbed in some way, to move from one state to another. A successful, predictive model should involve at least two elements: First, the model should include some index of the intensity of the perturbation that elicits the response; effective responses should, in some fashion, be linearly or nonlinearity related to perturbations. Second, the model should factor in subjects' abilities to meet the challenges posed by the perturbations. This review indicates that these two basic components of a successful model may be difficult to incorporate. In the simple case of passive upright tilt, blood pressure measurements may not accurately indicate the stimulus, because blood pressure reductions are reversed by rapidly occurring reflex blood pressure increases. Since not all subject populations respond identically to hemodynamic challenges, it also may be important to characterize baroreflex responsiveness, and include such a term in a model. Although vagal and sympathetic baroreflex responses to stereotyped challenges can be measured accurately, recent research points to extraordinary variability of baroreflex responsiveness. The complexities discussed in this review should be considered, whether they are, or even can be incorporated into cardiovascular models.
    Cardiovascular Engineering 04/2008; 8(1):5-13. · 0.81 Impact Factor
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    ABSTRACT: 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.
    The Journal of Physiology 03/2007; 579(Pt 3):799-810. · 4.38 Impact Factor
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    ABSTRACT: Linear and nonlinear indices of heart rate variability (HRV) have been shown to predict mortality in congestive heart failure (CHF). However, most nonlinear indices describe only the fractality or complexity of HRV but not the intrinsic chaotic properties. In the present study, we performed linear (time- and frequency-domain), complexity (sample entropy), fractal (detrended fluctuation analysis) and chaos (numerical titration) analyses on the HRV of 50 CHF patients from the United Kingdom heart failure evaluation and assessment of risk trial database. Receiver operating characteristic and survival analysis yielded the chaos level to be the best predictor of mortality (followed by low/high frequency power ratio, LF/HF), such that these indices were significant in both univariate and multivariate models. These results indicate the power of heart rate chaos analysis as a potential prognostic tool for CHF.
    Annual International Conference of the IEEE Engineering in Medicine and Biology Society; 01/2007
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    ABSTRACT: To present additional analysis of data from a previously published study showing that biofeedback training to increase heart rate variability (HRV) can be an effective component in asthma treatment. HRV and intervention-related changes in HRV are negatively correlated with age. Here we assess the effects of age on biofeedback effects for asthma. Ten sessions of HRV biofeedback were administered to 45 adults with asthma. Medication was prescribed by blinded physicians according to National Heart, Lung, and Blood Institute criteria. Medication needs were reassessed biweekly. Decreases in need for controller medication were independent of age. There were larger acute decreases in forced oscillation frequency dependence in the older group but larger increases in HRV variables in the younger group. Differences between age groups were smaller among subjects trained in pursed-lips abdominal breathing as well as biofeedback, than among those receiving only biofeedback. Age-related attenuation of biofeedback effects on cardiovascular variability does not diminish the usefulness of the method for treating asthma among older patients. Additional training in pursed-lips abdominal breathing obliterates the effects of age on HRV changes during biofeedback.
    Chest 03/2006; 129(2):278-84. · 7.13 Impact Factor
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    Dwain L Eckberg, Tom A Kuusela
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    ABSTRACT: 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.
    The Journal of Physiology 09/2005; 567(Pt 3):1011-9. · 4.38 Impact Factor
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    ABSTRACT: To explore the relation between non-invasive measures of cardiac function and sudden cardiac death, as well as the development and utility of an index integrating these variables to identify patients at increased risk of this mode of death. UK-HEART (United Kingdom-heart failure evaluation and assessment of risk trial) was a prospective study conducted between December 1993 and April 2000. The study was specifically designed to identify non-invasive markers of death and mode of death among patients with chronic heart failure. 8 UK general hospitals. Death and mode of death. 553 patients aged a mean (SD) of 63 (10) years, in New York Heart Association functional class 2.3 (0.02), recruited prospectively. After 2365 patient-years' follow up, 201 patients had died (67 suddenly). Predictors of sudden death were greater cardiothoracic ratio, QRS dispersion, QT dispersion corrected for rate (QTc) across leads V1-V6 on the 12 lead ECG, and the presence of non-sustained ventricular tachycardia. The hazard ratio and 95% confidence intervals (CI) of sudden death for a 10% increase in cardiothoracic ratio was 1.43 (95% CI 1.20 to 1.71), for a 10% increase in QRS dispersion 1.11 (95% CI 1.04 to 1.19), for the presence of non-sustained ventricular tachycardia 2.03 (95% CI 1.27 to 3.25), and for a 10% increase in QTc dispersion across leads V1-V6 1.03 (95% CI 1.00 to 1.07) (all p < 0.04). An index derived from these four factors performed well in identifying patients specifically at increased risk of sudden death. Results show that an index derived from three widely available non-invasive investigations has the potential to identify ambulant patients with chronic heart failure at increased risk of sudden death. This predictive tool could be used to target more sophisticated investigations or interventions aimed at preventing sudden death.
    Heart (British Cardiac Society) 10/2004; 90(10):1137-43. · 5.01 Impact Factor
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    ABSTRACT: 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.
    The Journal of Physiology 07/2004; 538(1):309 - 320. · 4.38 Impact Factor
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    ABSTRACT: 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 ≈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.
    The Journal of Physiology 07/2004; 544(2):653 - 664. · 4.38 Impact Factor
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    ABSTRACT: 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.
    Clinical physiology and functional imaging 12/2003; 23(6):307-13. · 1.20 Impact Factor
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    ABSTRACT: 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. To develop a prognostic index to identify outpatients with mild to moderate chronic heart failure at increased risk of death. 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. 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.
    European Journal of Heart Failure 08/2003; 5(4):489-97. · 5.25 Impact Factor
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    Dwain L Eckberg
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    ABSTRACT: 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.
    The Journal of Physiology 05/2003; 548(Pt 2):339-52. · 4.38 Impact Factor
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    ABSTRACT: 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. 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. 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.
    Journal of Cardiac Failure 05/2003; 9(2):93-9. · 3.32 Impact Factor

Publication Stats

6k Citations
698.96 Total Impact Points


  • 2013
    • Lancaster University
      • Department of Physics
      Lancaster, England, United Kingdom
  • 1989–2013
    • Virginia Commonwealth University
      • • School of Medicine
      • • Department of Internal Medicine
      Richmond, Virginia, United States
  • 2001
    • Unfallkrankenhaus Hamburg
      Hamburg, Hamburg, Germany
    • Brigham and Women's Hospital
      • Division of Renal Medicine
      Boston, MA, United States
    • Brown University
      • Department of Obstetrics and Gynecology
      Providence, RI, United States
  • 1997–2001
    • University of Turku
      • Department of Physiatrics
      Turku, Province of Western Finland, Finland
    • Technische Universität Berlin
      Berlín, Berlin, Germany
    • University of Oulu
      • Department of Internal Medicine
      Oulu, Oulu, Finland
  • 1990–2001
    • Richmond VA Medical Center
      Richmond, Virginia, United States
  • 2000
    • Michigan Technological University
      • Department of Biomedical Engineering
      Houghton, MI, United States
  • 1998
    • The Ohio State University
      • Department of Physiology and Cell Biology
      Columbus, OH, United States
  • 1996
    • Mayo Clinic - Rochester
      • Department of Anesthesiology
      Rochester, Minnesota, United States
    • Mayo Foundation for Medical Education and Research
      • Department of Anesthesiology
      Scottsdale, AZ, United States
  • 1994
    • Texas Biomedical Research Institute
      San Antonio, Texas, United States
  • 1992
    • Case Western Reserve University
      Cleveland, Ohio, United States
  • 1988–1990
    • Virginia Hospital Center
      Arlington, Virginia, United States