Reduced baroreflex control of heart period after bed rest is normalized by acute plasma volume restoration

Adaptation to spaceflight or head-down-tilt bed rest leads to hypovolemia and an apparent abnormality of baroreflex regulation of cardiac period. In a previous study, we demonstrated that both chronic (2 wk) head-down-tilt bed rest and acute induced hypovolemia led to similar impairments in spontaneous baroreflex control of cardiac period, suggesting that a reduction in plasma volume may be responsible for this abnormality after bed rest. Therefore we hypothesized that this reduced "baroreflex function" could be restored by intravenous volume infusion equivalent to the reduction in plasma volume after bed rest. Six healthy subjects underwent 2 wk of -6 degrees head-down bed rest. Beat-by-beat arterial blood pressure and ECG were recorded during 6 min of spontaneous respiration and fixed-rate breathing (0.2 Hz), and transfer function analysis between systolic blood pressure and R-R interval was performed. Plasma volume was measured with Evans blue dye, and cardiac filling pressures were directly measured (Swan-Ganz catheter). After bed rest, studies were repeated before and after plasma volume restoration, with which both plasma volume and left ventricular end-diastolic pressure were restored to pre-bed rest levels by intravenous dextran40 infusion (288 +/- 31 ml). Transfer function gain in the high-frequency range, used as an index of vagally mediated arterial-cardiac baroreflex function, decreased significantly (13.4 +/- 3.1 to 8.1 +/- 2.9 ms/mmHg, P < 0.05) after bed rest. However, reduced transfer function gain was normalized to the pre-bed rest level (12.2 +/- 3.6 ms/mmHg) after precise plasma volume restoration. This result confirms that reductions in plasma volume, rather than a unique autonomic nervous system adaptation to bed rest, are largely responsible for the observed changes in spontaneous arterial-cardiac baroreflex function after bed rest.     

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.     

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.     

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity

Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation on arterial baroreceptor sensitivity, determined as the alpha index between oscillations in systolic BP (SBP) generated by respiration and oscillations present in R-R intervals (RR) and in peripheral sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal volume increased from 478 +/- 24 to 1,499 +/- 84 ml and raised SBP from 118 +/- 2 to 125 +/- 3 mmHg, whereas RR decreased from 947 +/- 18 to 855 +/- 11 ms (all P < 0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex sensitivity to oscillations in SBP at both cardiac (from 13 +/- 1 to 9 +/- 1 ms/mmHg, P < 0.001) and MSNA levels (by -37 +/- 5%, P < 0.0001). Thus increased BP during hyperventilation does not elicit any reduction in either heart rate or MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation-induced BP oscillations is attenuated. Blunted baroreflex gain during hyperventilation may be a mechanism that facilitates simultaneous increases in BP, heart rate, and sympathetic activity during dynamic exercise and chemoreceptor activation.     

Neuropeptide Y reverses chronic stress-induced baroreflex hypersensitivity in rats

Chronic stress, as a risk factor for cardiovascular diseases, has been reported to result in elevated plasma neuropeptide Y (NPY) and be highly associated with abnormal cardiac autonomic function. This study aimed to explore the effect of NPY on the chronic stress-induced abnormal baroreceptor reflex sensitivity (BRS). Seven types of recognized stressors were used to develop chronic stress rat model. Subcutaneously implanting ALZET mini-osmotic pumps containing NPY were used to evaluate the action of NPY on the stressed male rats. We found that chronic stress showed no influence on baseline systolic blood pressure (SBP) and heart rate (HR), whereas NPY (85 μg for 30 days) could elevate baseline SBP and induce bradycardia in rats intervened by various stimuli. NPY pretreatment could preserve chronic stress-induced decreases in left ventricular systolic pressure (LVSP) and the maximum rate of change in left ventricular pressure in the isovolumic contraction period (+dp/dt(max)) but has shown no effect on left ventricular end diastolic pressure (LVEDP) and the maximum rate of change in left ventricular pressure in the isovolumic relaxation period (-dp/dt(max)). Notably, chronic stress led to baroreflex oversensitivity indicated by the elevated ratio of Δheart rate (HR)/ Δmean arterial blood pressure (MABP) in rats followed by vasoconstrictor (phenylephrine, PE) or vasodilator (sodium nitroprusside, SNP) administration, which was almost completely reversed by NPY pretreatment. The expressions of substance P (SP) and gamma aminobutyric acid A receptor (GABA(A)R) in nucleus tractus solitarius were increased in chronic stress rats, which were counteracted by NPY pretreatment. We conclude that chronic stress-induced baroreflex hypersensitivity could be blocked by NPY pretreatment. Furthermore, the altered expressions of neurotransmitters and receptors in the brainstem might contribute to this process.     

Blood pressure regulation in neurally intact human vs. acutely injured paraplegic and tetraplegic patients during passive tilt

We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to head-up tilt following spinal cord injury. We evaluated spectral power of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP) ramps, baroreflex sequences, and cross-correlation of SBP with heart rate (HR) in low (0.04-0.15 Hz)- and high (0.15-0.4 Hz)-frequency regions. During tilt, AB and PARA effectively regulated BP and HR, but TETRA did not. The numbers of SBP ramps and percentages of heartbeats involved in SBP ramps and baroreflex sequences increased in AB, were unchanged in PARA, and declined in TETRA. BRS was lowest in PARA and declined with tilt in all groups. BEI was greatest in AB and declined with tilt in all groups. Low-frequency power of BP and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA, and declined in TETRA. The peak cross-correlation magnitude in HF decreased with tilt in all groups. Our data indicate that spinal cord injury results in decreased stimulation of arterial baroreceptors and less engagement of feedback control as demonstrated by lower 1) spectral power of BP, 2) number (and percentages) of SBP ramps and barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI, and 5) changes in delay between SBP/HR. Diminished vasomotion and impaired baroreflex regulation may be major contributors to decreased orthostatic tolerance following injury.     

Enhanced open-loop but not closed-loop cardiac baroreflex sensitivity during orthostatic stress in humans

The neural interaction between the cardiopulmonary and arterial baroreflex may be critical for the regulation of blood pressure during orthostatic stress. However, studies have reported conflicting results: some indicate increases and others decreases in cardiac baroreflex sensitivity (i.e., gain) with cardiopulmonary unloading. Thus the effect of orthostatic stress-induced central hypovolemia on regulation of heart rate via the arterial baroreflex remains unclear. We sought to comprehensively assess baroreflex function during orthostatic stress by identifying and comparing open- and closed-loop dynamic cardiac baroreflex gains at supine rest and during 60° head-up tilt (HUT) in 10 healthy men. Closed-loop dynamic "spontaneous" cardiac baroreflex sensitivities were calculated by the sequence technique and transfer function and compared with two open-loop carotid-cardiac baroreflex measures using the neck chamber system: 1) a binary white-noise method and 2) a rapid-pulse neck pressure-neck suction technique. The gain from the sequence technique was decreased from -1.19 ± 0.14 beats·min(-1)·mmHg(-1) at rest to -0.78 ± 0.10 beats·min(-1)·mmHg(-1) during HUT (P = 0.005). Similarly, closed-loop low-frequency baroreflex transfer function gain was reduced during HUT (P = 0.033). In contrast, open-loop low-frequency transfer function gain between estimated carotid sinus pressure and heart rate during white-noise stimulation was augmented during HUT (P = 0.01). This result was consistent with the maximal gain of the carotid-cardiac baroreflex stimulus-response curve (from 0.47 ± 0.15 beats·min(-1)·mmHg(-1) at rest to 0.60 ± 0.20 beats·min(-1)·mmHg(-1) at HUT, P = 0.037). These findings suggest that open-loop cardiac baroreflex gain was enhanced during HUT. Moreover, under closed-loop conditions, spontaneous baroreflex analyses without external stimulation may not represent open-loop cardiac baroreflex characteristics during orthostatic stress.     

Alterations in autonomic function and cerebral hemodynamics to orthostatic challenge following a mountain marathon.

We examined potential mechanisms (autonomic function, hypotension, and cerebral hypoperfusion) responsible for orthostatic intolerance following prolonged exercise. Autonomic function and cerebral hemodynamics were monitored in seven athletes pre-, post- (<4 h), and 48 h following a mountain marathon [42.2 km; cumulative gain approximately 1,000 m; approximately 15 degrees C; completion time, 261 +/- 27 (SD) min]. In each condition, middle cerebral artery blood velocity (MCAv), blood pressure (BP), heart rate (HR), and cardiac output (Modelflow) were measured continuously before and during a 6-min stand. Measurements of HR and BP variability and time-domain analysis were used as an index of sympathovagal balance and baroreflex sensitivity (BRS). Cerebral autoregulation was assessed using transfer-function gain and phase shift in BP and MCAv. Hypotension was evident following the marathon during supine rest and on standing despite increased sympathetic and reduced parasympathetic control, and elevations in HR and cardiac output. On standing, following the marathon, there was less elevation in normalized low-frequency HR variability (P < 0.05), indicating attenuated sympathetic activation. MCAv was maintained while supine but reduced during orthostasis postmarathon [-10.4 +/- 9.8% pre- vs. -15.4 +/- 9.9% postmarathon (%change from supine); P < 0.05]; such reductions were related to an attenuation in BRS (r = 0.81; P < 0.05). Cerebral autoregulation was unchanged following the marathon. These findings indicate that following prolonged exercise, hypotension and postural reductions in autonomic function or baroreflex control, or both, rather than a compromise in cerebral autoregulation, may place the brain at risk of hypoperfusion. Such changes may be critical factors in collapse following prolonged exercise.     

Baroreflexes of the rat. III. Open-loop gain and electroencephalographic arousal

In early studies of humans, baroreflex sensitivity was found to be higher during sleep; however, subsequent observations in several species, including humans, have been at variance with the original reports. Sleep and arousal are behavioral states, and it is difficult to accurately and repeatedly measure baroreflex sensitivity in behaving animals. However, pharmacologically immobilized (neuromuscularly blocked) rats have apparently normal sleep-wakefulness cycles, and baroreflex gain can be measured directly in this preparation. Using the delta band of the EEG (EEG(delta)) as an index of sleep and arousal and open-loop aortic depressor nerve (ADN) stimulation as a baroreflex input, we found that blood pressure (BP) level depended on arousal (r = -0.416; P < 0.0001), and BP baroreflex gain depended on BP level (r = 0.496; P < 0.0001), but that BP baroreflex gain was independent of arousal (r = 0.001; NS). Heart period (HP) was different; although HP level depended on arousal (r = 0.352; P < 0.0001), HP baroreflex gain did not depend on HP level (r = 0.029; NS), and HP baroreflex gain increased with arousal (r = 0.315; P < 0.0001). A partial-correlations analysis showed that the presence of the relationship between BP level and BP baroreflex gain probably attenuated the relationship between arousal and BP gain. The results are consistent 1) with physiological findings showing that arousal attenuates afferent transmission through the nucleus of the solitary tract and enhances sympathoinhibition at the rostral ventrolateral medulla; and 2) with observations in humans and animals showing increased cardiac baroreflex sensitivity during sleep, but little if any effect of sleep on BP baroreflex sensitivity. The findings are relevant to all methods of baroreflex gain estimation that use HP as the index of baroreflex activation.     

Baroreflex stabilization of the double (pressure-rate) product at 0.05 Hz in conscious rabbits

The product of heart rate (HR) and systolic blood pressure (SBP), the double product (DP), is an indirect index of cardiac oxygen consumption. We used spectral analysis to test the hypothesis that baroreflex adjustments of HR stabilize the DP during spontaneous variations in SBP. SBP and HR were recorded by telemetry in five male conscious rabbits. HR and SBP power spectra each exhibited a low frequency peak at approximately 0.05 Hz that was associated with high (>0.5) spectral coherence and a positive phase relationship between SBP and HR (SBP leading). A prominent peak was absent in the spectra of their product, suggesting that SBP and HR interacted to reduce DP variability in this frequency region. In contrast, a prominent 0.05-Hz peak was present in the power spectrum of calculated surrogates of the DP in which reflex interactions between HR and SBP had been removed. Our results suggest that baroreflex adjustments of HR stabilize the DP during spontaneous low-frequency variations in SBP in conscious rabbits.     

Dynamic cardiorespiratory interaction during head-up tilt-mediated presyncope

In 28 healthy adults, we compared the dynamic interaction between respiration and cerebral autoregulation in 2 groups of subjects: those who did and did not develop presyncopal symptoms during 70 degrees passive head-up tilt (HUT), i.e., nonpresyncopal (23 subjects) and presyncopal (5 subjects). Airflow, CO2, cerebral blood flow velocity (CBF), ECG, and blood pressure (BP) were recorded. To determine whether influences of mean BP (MBP) and systolic SP (SBP) on CBF were altered in presyncopal subjects, coherencies and transfer functions between these variables and mean and peak CBF (CBFm and CBFp) were estimated. To determine the influence of end-tidal CO2 (ETco2) on CBF, the relative CO2 reactivity (%change in CBFm per mmHg change in ETco2) was calculated. We found that in presyncopal subjects before symptoms during HUT, coherence between SBP and CBFp was higher (P=0.02) and gains of transfer functions between BP (MBP and SBP) and CBFm were larger (MBP, P=0.01; SBP, P=0.01) in the respiratory frequency region. In the last 3 min before presyncope, presyncopals had a reduced relative CO2 reactivity (P=0.005), likely a consequence of the larger decrease in ETco2. We hypothesize that the CO2-mediated increase in resistance attenuates autoregulation such that the relationship between systemic and cerebral hemodynamics is enhanced. Our results suggest that an altered cardiorespiratory interaction involving cerebral hemodynamics may contribute in the cascade of events during tilt that culminate in unexplained syncope.     

Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism

Sedentary aging leads to increased cardiovascular stiffening, which can be ameliorated by sufficient amounts of lifelong exercise training. An even more extreme form of cardiovascular stiffening can be seen in heart failure with preserved ejection fraction (HFpEF), which comprises ~40~50% of elderly patients diagnosed with congestive heart failure. There are two major interrelated hypotheses proposed to explain heart failure in these patients: 1) increased left ventricular (LV) diastolic stiffness and 2) increased arterial stiffening. The beat-to-beat dynamic Starling mechanism, which is impaired with healthy human aging, reflects the interaction between ventricular and arterial stiffness and thus may provide a link between these two mechanisms underlying HFpEF. Spectral transfer function analysis was applied between beat-to-beat changes in LV end-diastolic pressure (LVEDP; estimated from pulmonary artery diastolic pressure with a right heart catheter) and stroke volume (SV) index. The dynamic Starling mechanism (transfer function gain between LVEDP and the SV index) was impaired in HFpEF patients (n = 10) compared with healthy age-matched controls (n = 12) (HFpEF: 0.23 ± 0.10 ml·m?2·mmHg?1 and control: 0.37 ± 0.11 ml·m?2·mmHg?1, means ± SD, P = 0.008). There was also a markedly increased (3-fold) fluctuation of LV filling pressures (power spectral density of LVEDP) in HFpEF patients, which may predispose to pulmonary edema due to intermittent exposure to higher pulmonary capillary pressure (HFpEF: 12.2 ± 10.4 mmHg2 and control: 3.8 ± 2.9 mmHg2, P = 0.014). An impaired dynamic Starling mechanism, even more extreme than that observed with healthy aging, is associated with marked breath-by-breath LVEDP variability and may reflect advanced ventricular and arterial stiffness in HFpEF, possibly contributing to reduced forward output and pulmonary congestion.     

Cardiovascular regulation during long-duration spaceflights to the International Space Station

Early evidence from long-duration flights indicates general cardiovascular deconditioning, including reduced arterial baroreflex gain. The current study investigated the spontaneous baroreflex and markers of cardiovascular control in six male astronauts living for 2-6 mo on the International Space Station. Measurements were made from the finger arterial pressure waves during spontaneous breathing (SB) in the supine posture pre- and postflight and during SB and paced breathing (PB, 0.1 Hz) in a seated posture pre- and postflight, as well as early and late in the missions. There were no changes in preflight measurements of heart rate (HR), blood pressure (BP), or spontaneous baroreflex compared with in-flight measurements. There were, however, increases in the estimate of left ventricular ejection time index and a late in-flight increase in cardiac output (CO). The high-frequency component of RR interval spectral power, arterial pulse pressure, and stroke volume were reduced in-flight. Postflight there was a small increase compared with preflight in HR (60.0 ± 9.4 vs. 54.9 ± 9.6 beats/min in the seated posture, P < 0.05) and CO (5.6 ± 0.8 vs. 5.0 ± 1.0 l/min, P < 0.01). Arterial baroreflex response slope was not changed during spaceflight, while a 34% reduction from preflight in baroreflex slope during postflight PB was significant (7.1 ± 2.4 vs. 13.4 ± 6.8 ms/mmHg), but a smaller average reduction (25%) during SB (8.0 ± 2.1 vs. 13.6 ± 7.4 ms/mmHg) was not significant. Overall, these data show no change in markers of cardiovascular stability during long-duration spaceflight and only relatively small changes postflight at rest in the seated position. The current program routine of countermeasures on the International Space Station provided sufficient stimulus to maintain cardiovascular stability under resting conditions during long-duration spaceflight.     

Breathing cardiovascular variability and baroreflex in mechanically ventilated patients

Heart rate and blood pressure variations during spontaneous ventilation are related to the negative airway pressure during inspiration. Inspiratory airway pressure is positive during mechanical ventilation, suggesting that reversal of the normal baroreflex-mediated pattern of variability may occur. We investigated heart rate and blood pressure variability and baroreflex sensitivity in 17 mechanically ventilated patients. ECG (RR intervals), invasive systolic blood pressure (SBP), and respiratory flow signals were recorded. High-frequency (HF) amplitude of RR and SBP time series and HF phase differences between RR, SBP, and ventilatory signals were continuously computed by Complex DeModulation (CDM). Cross-spectral analysis was used to assess the coherence and the gain functions between RR and SBP, yielding baroreflex sensitivity indices. The HF phase difference between SBP and ventilatory signals was nearly constant in all patients with inversion of SBP variability during the ventilator cycle compared with cycling with negative inspiratory pressure to replicate spontaneous breathing. In 12 patients (group 1), the phase difference between RR and ventilatory signals changed over time and the HF-RR amplitude varied. In the remaining five patients (group 2), RR-ventilatory signal phase and HF-RR amplitude showed little change; however, only one of these patients exhibited a RR-ventilatory signal phase difference mimicking the normal pattern of respiratory sinus arrhythmia. Spectral coherence between RR and SBP was lower in the group with phase difference changes. Positive pressure ventilation exerts mainly a mechanical effect on SBP, whereas its influence on HR variability seems more complex, suggesting a role for neural influences.     

Carotid and aortic baroreflexes of the rat: II. Open-loop frequency response and the blood pressure spectrum

To determine the relationship between blood pressure (BP) variability and the open-loop frequency domain transfer function (TF) of the baroreflexes, we measured the pre- and postsinoaortic denervation (SAD) spectra and the effects of periodic and step inputs to the aortic depressor nerve and isolated carotid sinus of central nervous system-intact, neuromuscular-blocked (NMB) rats. Similar to previous results in freely moving rats, SAD greatly increased very low frequency (VLF) (0.01-0.2 Hz) systolic blood pressure (SBP) noise power. Step response-frequency measurements for SBP; interbeat interval (IBI); venous pressure; mesenteric, femoral, and skin blood flow; and direct modulation analyses of SBP showed that only VLF variability could be substantially attenuated by an intact baroreflex. The -3-dB frequency for SBP is 0.035-0.056 Hz; femoral vascular conductance is similar to SBP, but mesenteric vascular conductance has a reliably lower and IBI has a reliably higher -3-dB point. The overall open-loop transportation lag, of which 相似文献   

Respiration drives phase synchronization between blood pressure and RR interval following loss of cardiovagal baroreflex during vasovagal syncope

Loss of the cardiovagal baroreflex (CVB), thoracic hypovolemia, and hyperpnea contribute to the nonlinear time-dependent hemodynamic instability of vasovagal syncope. We used a nonlinear phase synchronization index (PhSI) to describe the extent of coupling between cardiorespiratory parameters, systolic blood pressure (SBP) or arterial pressure (AP), RR interval (RR), and ventilation, and a directional index (DI) measuring the direction of coupling. We also examined phase differences directly. We hypothesized that AP-RR interval PhSI would be normal during early upright tilt, indicating intact CVB, but would progressively decrease as faint approached and CVB failed. Continuous measurements of AP, RR interval, respiratory plethysomography, and end-tidal CO2 were recorded supine and during 70-degree head-up tilt in 15 control subjects and 15 fainters. Data were evaluated during five distinct times: baseline, early tilt, late tilt, faint, and recovery. During late tilt to faint, fainters exhibited a biphasic change in SBP-RR interval PhSI. Initially in fainters during late tilt, SBP-RR interval PhSI decreased (fainters, from 0.65±0.04 to 0.24±0.03 vs. control subjects, from 0.51±0.03 to 0.48±0.03; P<0.01) but then increased at the time of faint (fainters=0.80±0.03 vs. control subjects=0.42±0.04; P<0.001) coinciding with a change in phase difference from positive to negative. Starting in late tilt and continuing through faint, fainters exhibited increasing phase coupling between respiration and AP PhSI (fainters=0.54±0.06 vs. control subjects=0.27±0.03; P<0.001) and between respiration and RR interval (fainters=0.54±0.05 vs. control subjects=0.37±0.04; P<0.01). DI indicated respiratory driven AP (fainters=0.84±0.04 vs. control subjects=0.39±0.09; P<0.01) and RR interval (fainters=0.73±0.10 vs. control subjects=0.23±0.11; P<0.001) in fainters. The initial drop in the SBP-RR interval PhSI and directional change of phase difference at late tilt indicates loss of cardiovagal baroreflex. The subsequent increase in SBP-RR interval PhSI is due to a respiratory synchronization and drive on both AP and RR interval. Cardiovagal baroreflex is lost before syncope and supplanted by respiratory reflexes, producing hypotension and bradycardia.     

Spontaneous baroreflex control of heart rate during exercise and muscle metaboreflex activation in heart failure

In heart failure (HF), there is a reduced baroreflex sensitivity at rest, and during dynamic exercise there is enhanced muscle metaboreflex activation (MRA). However, how the arterial baroreflex modulates HR during exercise is unknown. We tested the hypothesis that spontaneous baroreflex sensitivity (SBRS) is attenuated during exercise in HF and that MRA further depresses SBRS. In seven conscious dogs we measured heart rate (HR), cardiac output, and left ventricular systolic pressure at rest and during mild and moderate dynamic exercise, before and during MRA (via imposed reductions of hindlimb blood flow), and before and after induction of HF (by rapid ventricular pacing). SBRS was assessed by the sequences method. In control, SBRS was reduced from rest with a progressive resetting of the baroreflex stimulus-response relationship in proportion to exercise intensity and magnitude of MRA. In HF, SBRS was significantly depressed in all settings; however, the changes with exercise and MRA occurred with a pattern similar to the control state. As in control, the baroreflex stimulus-response relationship showed an intensity- and muscle metaboreflex (MMR)-dependent rightward and upward shift. The results of this study indicate that HF induces an impairment in baroreflex control of HR at rest and during exercise, although the effects of exercise and MRA on SBRS occur with a similar pattern as in control, indicating the persistence of some vagal activity.     

Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats x min(-1) x mmHg(-1)). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (-3.0 +/- 0.4 vs. -5.2 +/- 0.4, P<0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS (-2.1 +/- 0.1, P<0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (-1.2 +/- 0.1, P<0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS (-0.9 +/- 0.1, P<0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS.     

Arterial baroreflex function and cardiovascular variability: interactions and implications

The arterial baroreflex contributes importantly to the short-term regulation of blood pressure and cardiovascular variability. A number of factors (including reflex, humoral, behavioral, and environmental) may influence gain and effectiveness of the baroreflex, as well as cardiovascular variability. Many central neural structures are also involved in the regulation of the cardiovascular system and contribute to the integrity of the baroreflex. Consequently, brain injuries or ischemia may induce baroreflex impairment and deranged cardiovascular variability. Baroreflex dysfunction and deranged cardiovascular variability are also common findings in cardiovascular disease. A blunted baroreflex gain and impaired heart rate variability are predictive of poor outcome in patients with heart failure and myocardial infarction and may represent an early index of autonomic activation in left ventricular dysfunction. The mechanisms mediating these relationships are not well understood and may in part be the result of cardiac structural changes and/or altered central neural processing of baroreflex signals.     

Autonomic cardiovascular regulation in subjects with acute mountain sickness

The aims of this study were 1) to evaluate whether subjects suffering from acute mountain sickness (AMS) during exposure to high altitude have signs of autonomic dysfunction and 2) to verify whether autonomic variables at low altitude may identify subjects who are prone to develop AMS. Forty-one mountaineers were studied at 4,559-m altitude. AMS was diagnosed using the Lake Louise score, and autonomic cardiovascular function was explored using spectral analysis of R-R interval and blood pressure (BP) variability on 10-min resting recordings. Seventeen subjects (41%) had AMS. Subjects with AMS were older than those without AMS (P < 0.01). At high altitude, the low-frequency (LF) component of systolic BP variability (LF(SBP)) was higher (P = 0.02) and the LF component of R-R variability in normalized units (LF(RR)NU) was lower (P = 0.001) in subjects with AMS. After 3 mo, 21 subjects (43% with AMS) repeated the evaluation at low altitude at rest and in response to a hypoxic gas mixture. LF(RR)NU was similar in the two groups at baseline and during hypoxia at low altitude but increased only in subjects without AMS at high altitude (P < 0.001) and did not change between low and high altitude in subjects with AMS. Conversely, LF(SBP) increased significantly during short-term hypoxia only in subjects with AMS, who also had higher resting BP (P < 0.05) than those without AMS. Autonomic cardiovascular dysfunction accompanies AMS. Marked LF(SBP) response to short-term hypoxia identifies AMS-prone subjects, supporting the potential role of an exaggerated individual chemoreflex vasoconstrictive response to hypoxia in the genesis of AMS.