Acute fasting reduces tolerance to progressive central hypovolemia in humans.

Potential health benefits of an acute fast include reductions in blood pressure and increases in vagal cardiac control. These purported health benefits could put fasted humans at risk for cardiovascular collapse when exposed to central hypovolemia. The purpose of this study was to test the hypothesis that an acute 24-h fast (vs. 3-h postprandial) would reduce tolerance to central hypovolemia induced via lower body negative pressure (LBNP). We measured blood ketones (ß-OHB) to confirm a successful fast (n = 18). We recorded the electrocardiogram (ECG), beat-to-beat arterial pressure, muscle sympathetic nerve activity (MSNA; n = 7), middle cerebral artery blood velocity (MCAv), and forearm blood flow. Following a 5-min baseline, LBNP was increased by 15 mmHg until -60 mmHg and then increased by 10 mmHg in a stepwise manner until onset of presyncope. Each LBNP stage lasted 5-min. Data are expressed as means ± SE ß-OHB increased (ß-OHB; 0.12 ± 0.04 fed vs. 0.47 ± 0.11, P < 0.01 mmol/L fast). Tolerance to central hypovolemia was decreased by ∼10% in the fasted condition measured via total duration of negative pressure (1,370 [Formula: see text] 89 fed vs. 1,229 ± 94 s fast, P = 0.04), and was negatively associated with fasting blood ketones (R = -0.542, P = 0.02). During LBNP, heart rate and MSNA increased similarly, but in the fasted condition forearm vascular resistance was significantly reduced. Our results suggest that acute fasting reduces tolerance to central hypovolemia by blunting increases in peripheral resistance, indicating that prolonged fasting may hinder an individual's ability to compensate to a loss of blood volume.NEW & NOTEWORTHY An acute 24 h fasting reduces tolerance to central hypovolemia, and tolerance is negatively associated with blood ketone levels. Compared with a fed condition (3-h postprandial), fasted participants exhibited blunted peripheral vasoconstriction and greater reductions in stroke volume during stepwise lower body negative pressure. These findings suggest that a prolonged fast may lead to quicker decompensation during central hypovolemia.

Relationship Between Environmental Air Quality and Congenital Heart Defects.

BACKGROUND: Congenital heart defects (CHDs) affect 40,000 U.S. infants annually. One fourth of these infants have a critical CHD, requiring intervention within the first year of life for survival. Over 80% of CHDs have an unknown etiology. Fine particulate matter ≤2.5 (PM2.5) and ozone (O3) may be air pollutants associated with CHD. OBJECTIVES: The purpose of this study was to explore relationships between first-trimester maternal exposure to air pollutants PM2.5 and O3 and a critical CHD diagnosis. METHODS: A retrospective cohort study with nested case controls was conducted using data from January 1, 2014, to December 31, 2016, and consisted of 199 infants with a diagnosed critical CHD and 550 controls. Air pollution data were obtained from the U.S. Environmental Protection Agency air monitors. Geographic information system software was used to geocode monitoring stations and infant residential locations. Data analysis included frequencies, chi-square, independent t-test analysis, and binary logistic regression for two time periods: the entire first trimester (Weeks 1-12) and the critical exposure window (Weeks 3-8 gestation). RESULTS: Critical CHD odds were not significantly increased by exposure during the first trimester. However, weekly analyses revealed CHD odds were higher in Weeks 5 and 8 as PM2.5 increased and decreased in Week 11 with increased O3 exposure. DISCUSSION: Our study shows no evidence to support the overall association between air pollutants PM2.5 and O3 and a critical CHD diagnosis. However, analyses by week suggested vulnerability in certain weeks of gestation and warrant additional surveillance and study.

Beyond the Baroreflex: A New Measure of Autonomic Regulation Based on the Time-Frequency Assessment of Variability, Phase Coherence and Couplings.

For decades the role of autonomic regulation and the baroreflex in the generation of the respiratory sinus arrhythmia (RSA) - modulation of heart rate by the frequency of breathing - has been under dispute. We hypothesized that by using autonomic blockers we can reveal which oscillations and their interactions are suppressed, elucidating their involvement in RSA as well as in cardiovascular regulation more generally. R-R intervals, end tidal CO2, finger arterial pressure, and muscle sympathetic nerve activity (MSNA) were measured simultaneously in 7 subjects during saline, atropine and propranolol infusion. The measurements were repeated during spontaneous and fixed-frequency breathing, and apnea. The power spectra, phase coherence and couplings were calculated to characterise the variability and interactions within the cardiovascular system. Atropine reduced R-R interval variability (p < 0.05) in all three breathing conditions, reduced MSNA power during apnea and removed much of the significant coherence and couplings. Propranolol had smaller effect on the power of oscillations and did not change the number of significant interactions. Most notably, atropine reduced R-R interval power in the 0.145-0.6 Hz interval during apnea, which supports the hypothesis that the RSA is modulated by a mechanism other than the baroreflex. Atropine also reduced or made negative the phase shift between the systolic and diastolic pressure, indicating the cessation of baroreflex-dependent blood pressure variability. This result suggests that coherent respiratory oscillations in the blood pressure can be used for the non-invasive assessment of autonomic regulation.

Controlled breathing and autonomic rhythms: Influence of auditory versus visual cues.

We compared standard metrics of autonomic control in 20 humans (10 female) during spontaneous and controlled breathing. Subjects controlled breathing at 0.25 Hz following a metronome (auditory) or scrolling waveforms (visual). Respiratory rates and heart rates were lower during spontaneous breathing compared with auditory and visual. One heart rate variability metric was higher during visual compared with spontaneous breathing, but baroreflex sensitivity and muscle sympathetic nerve activity were not affected by breathing cues. A majority of subjects (86%) perceived that breathing to auditory cues was more difficult compared with visual cues, but this elevated perceived stress did not manifest physiologically.

Acute effects of electronic cigarettes on arterial pressure and peripheral sympathetic activity in young nonsmokers.

Electronic cigarettes (e-cigarettes) are marketed as an alternative to smoking for those who want to decrease the health risks of tobacco. Tobacco cigarettes increase heart rate (HR) and arterial pressure, while reducing muscle sympathetic nerve activity (MSNA) through sympathetic baroreflex inhibition. The acute effects of e-cigarettes on arterial pressure and MSNA have not been reported: our purpose was to clarify this issue. Using a randomized crossover design, participants inhaled on a JUUL e-cigarette containing nicotine (59 mg/mL) and a similar placebo e-cigarette (0 mg/mL). Experiments were separated by ∼1 mo. We recorded baseline ECG, finger arterial pressure (n = 15), and MSNA (n = 10). Subjects rested for 10 min (BASE) and then inhaled once every 30 s on an e-cigarette that contained nicotine or placebo (VAPE) for 10 min followed by a 10-min recovery (REC). Data were expressed as Δ means ± SE from BASE. Heart rate increased in the nicotine condition during VAPE and returned to BASE values in REC (5.0 ± 1.3 beats/min nicotine vs. 0.1 ± 0.8 beats/min placebo, during VAPE; P < 0.01). Mean arterial pressure increased in the nicotine condition during VAPE and remained elevated during REC (6.5 ± 1.6 mmHg nicotine vs. 2.6 ± 1 mmHg placebo, during VAPE and 4.6.0 ± 1.7 mmHg nicotine vs. 1.4 ± 1.4 mmHg placebo, during REC; P < 0.05). MSNA decreased from BASE to VAPE and did not restore during REC (-7.1 ± 1.6 bursts/min nicotine vs. 2.6 ± 2 bursts/min placebo, during VAPE and -5.8 ± 1.7 bursts/min nicotine vs. 0.5 ± 1.4 bursts/min placebo, during REC; P < 0.05). Our results show that acute e-cigarette usage increases mean arterial pressure leading to a baroreflex-mediated inhibition of MSNA.NEW & NOTEWORTHY The JUUL e-cigarette is the most popular e-cigarette in the market. In the present study, inhaling on a JUUL e-cigarette increased mean arterial pressure and heart rate, and decreased muscle sympathetic nerve activity (MSNA). In contrast, inhaling on a placebo e-cigarette without nicotine elicited no sympathomimetic effects. Although previous tobacco cigarette studies have demonstrated increased mean arterial pressure and MSNA inhibition, ours is the first study to report similar responses while inhaling on an e-cigarette. Listen to this article's corresponding podcast at @ https://ajpheart.podbean.com/e/aerosolized-nicotine-and-cardiovascular-control/.

Association of serum levels of p,p'- Dichlorodiphenyldichloroethylene (DDE) with type 2 diabetes in African American and Caucasian adult men from agricultural (Delta) and non-agricultural (non-Delta) regions of Mississippi.

Epidemiological associations were reported in several studies between persistent organochlorine organic pollutants and type 2 diabetes mellitus (T2D). Mississippi is a highly agricultural state in the USA, particularly the Delta region, with previous high usage of organochlorine (OC) insecticides such as p,p'- dichlorodiphenyltrichloroethane (DDT). In addition, there is a high proportion of African Americans who display elevated prevalence of T2D. Therefore, this State provides an important dataset for further investigating any relationship between OC compounds and metabolic diseases. The aim of this study was to assess whether soil and serum levels of OC compounds, such as p,p'- dichlorodiphenyldichloroethylene (DDE), arising from the heavy historical use of legacy OC insecticides, might serve as an environmental public health indicator for T2D occurrence. Soil samples from 60 Delta and 60 non-Delta sites randomly selected were analyzed for the presence of OC compounds. A retrospective cohort study of adult men (150 from each region) was recruited to provide a blood sample for OC compound quantitation and select demographic and clinical information including T2D. Using multivariable logistic regression, an association was found between increasing serum DDE levels and T2D occurrence in non-Delta participants (those subjects with lower serum DDE levels), as opposed to Delta participants (individuals with higher serum DDE levels). Thus, while there was a relationship between serum DDE levels and T2D in those with lower burdens of DDE, the lack of association in those with higher levels of DDE indicates a complex non-monotonic correlation between serum DDE levels and T2D occurrence complicating the goal of finding a public health marker for T2D. Abbreviations: BMI, body mass index; CVD, cardiovascular disease; CDC, Center for Disease Control, United States of America; DDE, p,p'- dichlorodiphenyldichloroethylene; DDT, p,p'- dichlorodiphenyltrichloroethane; GC/MS, gas chromatography/mass spectrometry; GIS, geographic information system; GPS, global positioning system; HDL, high-density lipoprotein; HTN, hypertension; IDW, inverse distance weighting; IRB, Institutional Review Board; LDL, low-density lipoprotein; LOQ, limit of quantitation; NHANES, National Health and Nutrition Examination Surveys; POPs, persistent organic pollutants; OC, organochlorine; PCB, polychlorinated biphenyl; SIM, single-ion monitoring; T2D, type 2 diabetes mellitus; USA, United States of America.

Effects of Acute Vaporized Nicotine in Non-Tobacco Users at Rest and during Exercise.

Smokers, and even non-smokers, may utilize vaporized nicotine delivered by electronic cigarette (EC) due to the perception that EC are "healthier" than traditional tobacco cigarettes. The effects of vaporized nicotine delivered by EC on resting blood pressure (BP) and resting metabolic rate (RMR), or BP and aerobic power during exercise have not been studied. This investigation tested the effects of acute vaporized nicotine inhalation by EC on resting BP and RMR and cycle exercise BP, metabolic responses, and aerobic power in young, normotensive non-smokers. Using a double-blind design, 20 subjects (10 female) participated in two randomized trials: placebo (0 mg nicotine) or nicotine (18 mg nicotine). Participants inhaled from EC once every 30 s for 10 min (20 inhalations total). RMR was assessed 40 min later by indirect calorimetry followed by an incremental cycle test. RMR was not different between trials (p=0.79). Compared to the placebo, resting diastolic pressure (DBP) was 3 mmHg higher with nicotine (p=0.04). VO2peak was not different between the nicotine trial (2.3±0.8 L•min-1) and placebo (2.3±0.7 L•min-1) trials (p=0.77), and Wmax was also similar between nicotine (201.0±53.8 W) and the placebo (204.8±57.8 W) (p=0.29). During the cycle exercise test, average DBP was higher following nicotine use compared with placebo trial (p=0.05), and exercise DBPpeak after nicotine (79.4±7.6) was significantly higher than placebo (74.9±8.3 mmHg) (p=0.02). Resting systolic blood pressure (SBP) was 3.7 mmHg lower for nicotine trial (p=0.04) but no SBP treatment effect was observed during exercise (p=0.14). Our results show that acute vaporized nicotine inhalation via EC increases resting and exercise DBP but does not affect RMR or cycle aerobic power in young, normotensive non-smokers.

Respiratory modulation of human autonomic function on Earth.

KEY POINTS: We studied healthy supine astronauts on Earth with electrocardiogram, non-invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings. The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs. R-R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea. The subjects' responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity. ABSTRACT: We studied eight healthy, supine astronauts on Earth, who followed a simple protocol: they breathed at fixed or random frequencies, hyperventilated and then stopped breathing, as a means to modulate and expose to view important, but obscure central neurophysiological mechanisms. Our recordings included the electrocardiogram, finger photoplethysmographic arterial pressure, tidal volume, respiratory carbon dioxide concentrations and peroneal nerve muscle sympathetic activity. Arterial pressure, vagal tone and muscle sympathetic outflow were comparable during spontaneous and controlled-frequency breathing. Compared with spontaneous, 0.1 and 0.05 Hz breathing, however, breathing at usual frequencies (∼0.25 Hz) lowered arterial baroreflex gain, and provoked smaller arterial pressure and R-R interval fluctuations, which were separated by intervals that were likely to be too short and variable to be attributed to baroreflex physiology. R-R interval fluctuations at usual breathing frequencies disappear during apnoea, and thus cannot provide evidence for the existence of a central respiratory oscillation. Apnoea sets in motion a continuous and ever changing reorganization of the relations among stimulatory and inhibitory inputs and autonomic outputs, which, in our study, could not be attributed to altered chemoreceptor, baroreceptor, or pulmonary stretch receptor activity. We suggest that responses of healthy subjects to apnoea are driven importantly, and possibly prepotently, by changes of central respiratory motoneurone activity. The companion article extends these observations and asks the question, Might terrestrial responses to our 20 min breathing protocol find expression as long-term neuroplasticity in serial measurements made over 20 days during and following space travel?

Respiratory modulation of human autonomic function: long-term neuroplasticity in space.

KEY POINTS: We studied healthy astronauts before, during and after the Neurolab Space Shuttle mission with controlled breathing and apnoea, to identify autonomic changes that might contribute to postflight orthostatic intolerance. Measurements included the electrocardiogram, finger photoplethysmographic arterial pressure, respiratory carbon dioxide levels, tidal volume and peroneal nerve muscle sympathetic activity. Arterial pressure fell and then rose in space, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations rose and then fell in space, and descended to preflight levels upon return to Earth. Sympathetic burst frequencies (but not areas) were greater than preflight in space and on landing day, and astronauts' abilities to modulate both burst areas and frequencies during apnoea were sharply diminished. Spaceflight triggers long-term neuroplastic changes reflected by reciptocal sympathetic and vagal motoneurone responsiveness to breathing changes. ABSTRACT: We studied six healthy astronauts five times, on Earth, in space on the first and 12th or 13th day of the 16 day Neurolab Space Shuttle mission, on landing day, and 5-6 days later. Astronauts followed a fixed protocol comprising controlled and random frequency breathing and apnoea, conceived to perturb their autonomic function and identify changes, if any, provoked by microgravity exposure. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations and volumes, and peroneal nerve muscle sympathetic activity on Earth (in the supine position) and in space. (Sympathetic nerve recordings were made during three sessions: preflight, late mission and landing day.) Arterial pressure changed systematically from preflight levels: pressure fell during early microgravity exposure, rose as microgravity exposure continued, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations (root mean square of successive normal R-R intervals; and proportion of successive normal R-R intervals greater than 50 ms, divided by the total number of normal R-R intervals) rose significantly during early microgravity exposure, fell as microgravity exposure continued, and descended to preflight levels upon return to Earth. Sympathetic mechanisms also changed. Burst frequencies (but not areas) during fixed frequency breathing were greater than preflight in space and on landing day, but their control during apnoea was sharply altered: astronauts increased their burst frequencies from already high levels, but they could not modulate either burst areas or frequencies appropriately. Space travel provokes long-lasting sympathetic and vagal neuroplastic changes in healthy humans.

Cerebral Blood Flow Velocity During Combined Lower Body Negative Pressure and Cognitive Stress.

BACKGROUND: Lower body negative pressure (LBNP) decreases middle cerebral artery blood velocity (MCAv) and can induce hypotension. Mental stress increases MCAv, but the MCAv response to combined LBNP and mental stress (COMBO) is unknown. We hypothesized that performing a stressful cognitive challenge (i.e., mental stress) concurrently with LBNP would prevent LBNP-induced reductions of MCAv. METHODS: There were 18 subjects (9 men, 9 women; ages 20.1±0.3 yr) who completed 3 randomized 3-min trials: 1) LBNP (-40 mmHg); 2) mental stress (serial subtraction); and 3) COMBO (LBNP+mental stress). All reported values are mean±SE. Mean arterial pressure (MAP), heart rate (HR), forearm blood flow (FBF), and MCAv were measured continuously. Subjects also reported perceived stress following the mental stress and COMBO trials. RESULTS: LBNP decreased MAP (Δ-1.4±0.5 mmHg), MCAv (Δ-2.6±1.1 cm s(-1)) and FBF (Δ-0.8±0.1 units), and increased HR (Δ2.7±1.2 bpm). Mental stress increased MAP (Δ10.1±1.3 mmHg), HR (Δ17.4±2.2 bpm), and FBF (Δ2.4±0.4 units), while MCAv (Δ2.8±1.3 cm s(-1)) tended to increase. COMBO increased MAP (Δ5.3±2.3 mmHg) and HR (Δ21.3±2.6 bpm), and tended to increase FBF (Δ0.5±0.3 units). However, MCAv (Δ-4.6±2.0 cm s(-1)) decreased during COMBO. Decreases in MCAv during COMBO were not statistically different from LBNP-induced decreases (Δ-4.6±2.0 vs. Δ-2.6±1.1 cm s(-1)). Subjective ratings of perceived stress (standard 0 to 4 scale) tended to be higher during COMBO than mental stress (2.9±0.1 vs. 2.5±0.1 units). CONCLUSION: Our results suggest that mental stress does not effectively preserve MCAv when combined with central hypovolemia (i.e., LBNP).

Acute inhalation of vaporized nicotine increases arterial pressure in young non-smokers: a pilot study.

PURPOSE: Electronic cigarettes are growing in popularity, but the physiological consequences of vaporized nicotine are unknown. METHODS: Twenty healthy non-smokers inhaled vaporized nicotine and placebo (randomized). RESULTS: Nicotine inhalation was associated with higher arterial pressures in the seated position, and increased arterial pressures in the head-up positions with no other effects on autonomic control. CONCLUSIONS: Our results show that vaporized nicotine inhalation is not innocuous. Longitudinal studies in otherwise healthy non-smokers should be conducted.

Cardiovascular and cerebrovascular responses to progressive central hypovolemia in young smokers: a preliminary study.

The purpose of this study was to describe cardiovascular and cerebrovascular responses of smokers and nonsmokers to progressive central hypovolemia. Twenty subjects participated (equal male and female). We recorded the electrocardiogram, beat-to-beat arterial pressure (Finometer), cerebral blood velocity of the middle cerebral artery (transcranial Doppler), and end-tidal CO2. Lower body negative pressure (LBNP) was applied at 3 mm Hg · min(-1) for 20 minutes to an ending pressure of -60 mm Hg, and data were averaged in 2-minute bins. Arterial pressures were similar between groups at baseline, but heart rates tended to be higher, and stroke volumes and cerebral velocities tended to be lower in smokers at baseline and during LBNP (all p ≥ 0.17). Heart rates increased, and arterial pressures, stroke volumes, and cerebral velocities decreased during LBNP (all p ≤ 0.05), but responses were not different between smokers and nonsmokers. During the final stage of LBNP, systolic pressures and mean middle cerebral artery velocities were substantially lower in smokers than nonsmokers: these preliminary data may suggest clinical relevance of smoking status, but the magnitude of differences between groups were not distinguishable statistically. We therefore conclude that smokers and nonsmokers respond similarly to progressive central hypovolemia.

Determination of Anaerobic Threshold by Heart Rate or Heart Rate Variability using Discontinuous Cycle Ergometry.

The purpose was to determine if heart rate (HR) and heart rate variability (HRV) responses would reflect anaerobic threshold (AT) using a discontinuous, incremental, cycle test. AT was determined by ventilatory threshold (VT). Cyclists (30.6±5.9y; 7 males, 8 females) completed a discontinuous cycle test consisting of 7 stages (6 min each with 3 min of rest between). Three stages were performed at power outputs (W) below those corresponding to a previously established AT, one at W corresponding to AT, and 3 at W above those corresponding to AT. The W at the intersection of the trend lines was considered each metric's "threshold". The averaged stage data for Ve, HR, and time- and frequency-domain HRV metrics were plotted versus W. The W at the "threshold" for the metrics of interest were compared using correlation analysis and paired-sample t-test. In all, several heart rate-related parameters accurately reflected AT with significant correlations (p≤0.05) were observed between AT W and HR, mean RR interval (MRR), low and high frequency spectral energy (LF and HR, respectively), high frequency peak (fHF), and HFxfHF metrics' threshold W (i.e., MRRTW, etc.). Differences in HR or HRV metric threshold W and AT for all subjects were less than 14 W. The steady state data from discontinuous protocols may allow for a true indication of steady-state physiologic stress responses and corresponding W at AT, compared to continuous protocols using 1-2 min exercise stages.

Time-frequency methods and voluntary ramped-frequency breathing: a powerful combination for exploration of human neurophysiological mechanisms.

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 are 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 it 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.

Sympathetic responses to central hypovolemia: new insights from microneurographic recordings.

Hemorrhage remains a major cause of mortality following traumatic injury in both military and civilian settings. Lower body negative pressure (LBNP) has been used as an experimental model to study the compensatory phase of hemorrhage in conscious humans, as it elicits central hypovolemia like that induced by hemorrhage. One physiological compensatory mechanism that changes during the course of central hypovolemia induced by both LBNP and hemorrhage is a baroreflex-mediated increase in muscle sympathetic nerve activity (MSNA), as assessed with microneurography. The purpose of this review is to describe recent results obtained using microneurography in our laboratory as well as those of others that have revealed new insights into mechanisms underlying compensatory increases in MSNA during progressive reductions in central blood volume and how MSNA is altered at the point of hemodynamic decompensation. We will also review recent work that has compared direct MSNA recordings with non-invasive surrogates of MSNA to determine the appropriateness of using such surrogates in assessing the clinical status of hemorrhaging patients.

Sex differences in hemodynamic and sympathetic neural firing patterns during orthostatic challenge in humans.

Recent evidence suggests that young men and women may have different strategies for regulating arterial blood pressure, and the purpose of the present study was to determine if sex differences exist in diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA) relations during simulated orthostatic stress. We hypothesized that young men would demonstrate stronger DAP-MSNA coherence and a greater percentage of "consecutive integrated bursts" during orthostatic stress. Fourteen men and 14 women (age 23 ± 1 yr) were examined at rest and during progressive lower body negative pressure (LBNP; -5 to -40 mmHg). Progressive LBNP did not alter mean arterial pressure (MAP) in either sex. Heart rate increased and stroke volume decreased to a greater extent during LBNP in women (interactions, P < 0.05). DAP-MSNA coherence was strong (i.e., r ≥ 0.5) at rest and increased throughout all LBNP stages in men. In contrast, DAP-MSNA coherence was lower in women, and responses to progressive LBNP were attenuated compared with men (time × sex, P = 0.029). Men demonstrated a higher percentage of consecutive bursts during all stages of LBNP (sex, P < 0.05), although the percentage of consecutive bursts increased similarly during progressive LBNP between sexes. In conclusion, men and women demonstrate different firing patterns of integrated MSNA during LBNP that appear to be related to differences in DAP oscillatory patterns. Men tend to have more consecutive bursts, which likely contribute to a stronger DAP-MSNA coherence. These findings may help explain why young women are more prone to orthostatic intolerance.

Effects of dehydration on cerebrovascular control during standing after heavy resistance exercise.

We tested the hypothesis that dehydration exacerbates reductions of middle cerebral artery blood velocity (MCAv) and alters cerebrovascular control during standing after heavy resistance exercise. Ten males participated in two trials under 1) euhydration (EUH) and 2) dehydration (DEH; fluid restriction + 40 mg furosemide). We recorded finger photoplethysmographic arterial pressure and MCAv (transcranial Doppler) during 10 min of standing immediately after high-intensity leg press exercise. Symptoms (e.g., lightheadedness) were ranked by subjects during standing (1-5 scale). Low-frequency (LF) oscillations of mean arterial pressure (MAP) and mean MCAv were calculated as indicators of cerebrovascular control. DEH reduced plasma volume by 11% (P = 0.002; calculated from hemoglobin and hematocrit). During the first 30 s of standing after exercise, subjects reported greater symptoms during DEH vs. EUH (P = 0.05), but these were mild and resolved at 60 s. While MAP decreased similarly between conditions immediately after standing, MCAv decreased more with DEH than EUH (P = 0.02). With prolonged standing under DEH, mean MCAv remained below baseline (P ≤ 0.01), and below EUH values (P ≤ 0.05). LF oscillations of MAP were higher for DEH at baseline and during the entire 10 min of stand after exercise (P ≤ 0.057), while LF oscillations in mean MCAv were distinguishable only at baseline and 5 min following stand (P = 0.05). Our results suggest that mean MCAv falls below a "symptomatic threshold" in the acute phase of standing after exercise during DEH, although symptoms were mild and transient. During the prolonged phase of standing, increases in LF MAP and mean MCAv oscillations with DEH may help to maintain cerebral perfusion despite absolute MCAv remaining below the symptomatic threshold.

Linear mixed-effects modeling of the relationship between heart rate variability and fatigue arising from sleep deprivation.

INTRODUCTION: Fatigue degrades cognitive performance, yet there is no universally accepted objective measure of fatigue. We tested whether fatigue arising from sleep deprivation can be quantified objectively using heart rate variability (HRV). METHODS: There were 35 male subjects (mean +/- SD; age = 21.4 +/- 2.6 yr) who were assigned to one of two experimental groups: (1) control (N = 16), or (2) 48-h sleep-deprived (N=19). Using 3-h sampling intervals, we simultaneously tracked fatigue level, cognitive performance, and HRV. Linear mixed-effects (LME) models were used to evaluate linear relationships between fatigue level and cognitive performance, as well as between fatigue level and HRV. RESULTS: Significant negative slopes were observed in LME models of cognitive performance and fatigue level. Of the several HRV parameters examined during standing and supine rest, the ratio of low-frequency to high-frequency R-R interval in the supine position had the clearest significant relationship when modeled against fatigue level. DISCUSSION: In summary, our results suggest that HRV tracks fatigue arising from sleep deprivation. This noninvasive, objective tool can quantify fatigue in real time.

Arterial pressure oscillations are not associated with muscle sympathetic nerve activity in individuals exposed to central hypovolaemia.

The spectral power of low frequency oscillations of systolic arterial pressure (SAP(LF)) has been used as a non-invasive surrogate of muscle sympathetic nerve activity (MSNA) in both experimental and clinical situations. For SAP(LF) to be used in this way, a relationship must exist between SAP(LF) and MSNA within individuals during sympathetic activation. Using progressive central hypovolaemia to induce sympathetic activation, we hypothesised that SAP(LF) would correlate with MSNA in all subjects. ECG, beat-by-beat arterial pressure and MSNA were recorded in humans (n = 20) during a progressive lower body negative pressure (LBNP) protocol designed to cause presyncope in all subjects. Arterial pressure oscillations were assessed in the low frequency (LF; 0.04-0.15 Hz) domain using a Fourier transform. For the entire group, SAP(LF), MSNA burst frequency, and total MSNA increased during LBNP. Values for coefficients of determination (r(2)) describing the linear associations of SAP(LF) with MSNA burst frequency and total MSNA were 0.73 and 0.84, but rose to 0.89 and 0.98 when curvilinear fits were used, indicating that the relationship is curvilinear rather than linear. Associations between SAP(LF) and MSNA within each individual subject, however, varied widely for both MSNA burst frequency and total MSNA, whether derived by linear (r(2) range, 1.7 × 10(-6) to 0.99) or polynomial (r(2) range, 0.09 to 1.0) regression analysis. Similar results were obtained when relationships between low frequency oscillations in diastolic arterial pressure and MSNA were evaluated. These results do not support the use of low frequency oscillations in arterial pressure as a non-invasive measure of sympathetic outflow for individual subjects during sympathetic activation.