Hemodynamic and autonomic correlates of postexercise hypotension in patients with mild hypertension

We investigated the interplay of neural and hemodynamic mechanisms in postexercise hypotension (PEH) in hypertension. In 15 middle-aged patients with mild essential hypertension, we evaluated blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR), forearm (FVR) and calf vascular resistance (CVR), and autonomic function [by spectral analysis of R-R interval and BP variabilities and spontaneous baroreflex sensitivity (BRS)] before and after maximal exercise. Systolic and diastolic BP, TPR, and CVR were significantly reduced from baseline 60-90 min after exercise. CO, FVR, and HR were unchanged. The low-frequency (LF) component of BP variability increased significantly after exercise, whereas the LF component of R-R interval variability was unchanged. The overall change in BRS was not significant after exercise vs. baseline, although a significant, albeit small, BRS increase occurred in response to hypotensive stimuli. These findings indicate that in hypertensive patients, PEH is mediated mainly by a peripheral vasodilation, which may involve metabolic factors linked to postexercise hyperemia in the active limbs. The vasodilator effect appears to override a concomitant, reflex sympathetic activation selectively directed to the vasculature, possibly aimed to counter excessive BP decreases. The cardiac component of arterial baroreflex is reset during PEH, although the baroreflex mechanisms controlling heart period appear to retain the potential for greater opposition to hypotensive stimuli.     

Oxytocinergic regulation of cardiovascular function: studies in oxytocin-deficient mice

Oxytocin (OT) has been implicated in the cardiovascular responses to exercise, stress, and baroreflex adjustments. Studies were conducted to determine the effect of genetic manipulation of the OT gene on blood pressure (BP), heart rate (HR), and autonomic/baroreflex function. OT knockout (OTKO -/-) and control +/+ mice were prepared with chronic arterial catheters. OTKO -/- mice exhibited a mild hypotension (102 +/- 3 vs. 110 +/- 3 mmHg). Sympathetic and vagal tone were tested using beta(1)-adrenergic and cholinergic blockade (atenolol and atropine). Magnitude of sympathetic and vagal tone to the heart and periphery was not significantly different between groups. However, there was an upward shift of sympathetic tone to higher HR values in OTKO -/- mice. This displacement combined with unchanged basal HR led to larger responses to cholinergic blockade (+77 +/- 25 vs. +5 +/- 15 beats/min, OTKO -/- vs. control +/+ group). There was also an increase in baroreflex gain (-13.1 +/- 2.5 vs. -4.1 +/- 1.2 beats x min(-1) x mmHg(-1), OTKO -/- vs. control +/+ group) over a smaller BP range. Results show that OTKO -/- mice are characterized by 1) hypotension, suggesting that OT is involved in tonic BP maintenance; 2) enhanced baroreflex gain over a small BP range, suggesting that OT extends the functional range of arterial baroreceptor reflex; and 3) shift in autonomic balance, indicating that OT reduces the sympathetic reserve.     

Mechanisms of orthostatic intolerance following very prolonged exercise.

Nine men completed a 24-h exercise trial, with physiological testing sessions before (T1, approximately 0630), during (T2, approximately 1640; T3, approximately 0045; T4, approximately 0630), and 48-h afterwards (T5, approximately 0650). Participants cycled and ran/trekked continuously between test sessions. A 24-h sedentary control trial was undertaken in crossover order. Within testing sessions, participants lay supine and then stood for 6 min, while heart rate variability (spectral analysis of ECG), middle cerebral artery perfusion velocity (MCAv), mean arterial pressure (MAP; Finometer), and end-tidal Pco(2) (Pet(CO(2))) were measured, and venous blood was sampled for cardiac troponin I. During the exercise trial: 1) two, six, and four participants were orthostatically intolerant at T2, T3, and T4, respectively; 2) changes in heart rate variability were only observed at T2; 3) supine MAP (baseline = 81 +/- 6 mmHg) was lower (P < 0.05) by 14% at T3 and 8% at T4, whereas standing MAP (75 +/- 7 mmHg) was lower by 16% at T2, 37% at T3, and 15% at T4; 4) Pet(CO(2)) was reduced (P < 0.05) at all times while supine (-3-4 Torr) and standing (-4-5 Torr) during exercise trial; 5) standing MCAv was reduced (P < 0.05) by 23% at T3 and 30% at T4 during the exercise trial; 6) changes in MCAv with standing always correlated (P < 0.01) with changes in Pet(CO(2)) (r = 0.78-0.93), but only with changes in MAP at T1, T2, and T3 (P < 0.05; r = 0.62-0.84); and 7) only two individuals showed minor elevations in cardiac troponin I. Recovery was complete within 48 h. During prolonged exercise, postural-induced hypotension and hypocapnia exacerbate cerebral hypoperfusion and facilitate syncope.     

Cyclosporine attenuates the autonomic modulation of reflex chronotropic responses in conscious rats

Cyclosporine A (CyA), an immunosuppressant drug, has been shown to attenuate the baroreflex control of heart rate (HR). This study investigated whether or not the CyA-induced baroreflex dysfunction is due to alterations in the autonomic (sympathetic and parasympathetic) control of the heart. We evaluated the effect of muscarinic or beta-adrenergic blockade by atropine and propranolol, respectively, on reflex HR responses in conscious rats treated with CyA (20 mg x kg(-1) x day(-1) dissolved in sesame oil) for 11-13 days or the vehicle. Baroreflex curves relating changes in HR to increases or decreases in blood pressure (BP) evoked by phenylephrine (PE) and sodium nitroprusside (NP), respectively, were constructed and the slopes of the curves were taken as a measure of baroreflex sensitivity (BRS(PE) and BRS(NP)). Intravenous administration of PE and NP produced dose-related increases and decreases in BP, respectively, that were associated with reciprocal changes in HR. CyA caused significant (P < 0.05) reductions in reflex HR responses as indicated by the smaller BRS(PE) (-0.97 +/- 0.07 versus -1.47 +/- 0.10 beats x min(-1) x mmHg(-1) (1 mmHg = 133.322 Pa)) and BRS(NP) (-2.49 +/- 0.29 versus -5.23 +/- 0.42 beats x min(-1) x mmHg(-1)) in CyA-treated versus control rats. Vagal withdrawal evoked by muscarinic blockade elicited significantly lesser attenuation of BRS(PE) in CyA compared with control rats (40.2 +/- 8.0 versus 57.7 +/- 4.4%) and abolished the BRS(PE) difference between the two groups, suggesting that CyA reduces vagal activity. CyA also appears to impair cardiac sympathetic control because blockade of beta-adrenergic receptors by propranolol was less effective in reducing reflex tachycardic responses in CyA compared with control rats (41.6 +/- 4.2 versus 59.5 +/- 4.5%). These findings confirm earlier reports that CyA attenuates the baroreceptor control of HR. More importantly, the study provides the first pharmacological evidence that CyA attenuates reflex chronotropic responses via impairment of the autonomic modulation of the baroreceptor neural pathways.     

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.     

Arterial baroreflex control of heart rate during exercise in postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) have excessive tachycardia without hypotension during orthostasis as well as exercise. We tested the hypothesis that excessive tachycardia during exercise in POTS is not related to abnormal baroreflex control of heart rate (HR). Patients (n = 13) and healthy controls (n = 10) performed graded cycle exercise at 25, 50, and 75 W in both supine and upright positions while arterial pressure (arterial catheter) and HR (ECG) were measured. Baroreflex sensitivity of HR was assessed by bolus intravenous infusion of phenylephrine at each workload. In both positions, HR was higher in the patients than the controls during exercise. Supine baroreflex sensitivity (HR/systolic pressure) in POTS patients was -1.3 +/- 0.1 beats.min(-1).mmHg(-1) at rest and decreased to -0.6 +/- 0.1 beats.min(-1).mmHg(-1) during 75-W exercise, neither significantly different from the controls (P > 0.6). In the upright position, baroreflex sensitivity in POTS patients at rest (-1.4 +/- 0.1 beats.min(-1).mmHg(-1)) was higher than the controls (-1.0 +/- 0.1 beats.min(-1).mmHg(-1)) (P < 0.05), and it decreased to -0.1 +/- 0.04 beats.min(-1).mmHg(-1) during 75-W exercise, lower than the controls (-0.3 +/- 0.09 beats.min(-1).mmHg(-1)) (P < 0.05). The reduced arterial baroreflex sensitivity of HR during upright exercise was accompanied by greater fluctuations in systolic and pulse pressure in the patients than in the controls with 56 and 90% higher coefficient of variations, respectively (P < 0.01). However, when baroreflex control of HR was corrected for differences in HR, it was similar between the patients and controls during upright exercise. These results suggest that the tachycardia during exercise in POTS was not due to abnormal baroreflex control of HR.     

Alterations in cerebral autoregulation and cerebral blood flow velocity during acute hypoxia: rest and exercise

We examined the relationship between changes in cardiorespiratory and cerebrovascular function in 14 healthy volunteers with and without hypoxia [arterial O(2) saturation (Sa(O(2))) approximately 80%] at rest and during 60-70% maximal oxygen uptake steady-state cycling exercise. During all procedures, ventilation, end-tidal gases, heart rate (HR), arterial blood pressure (BP; Finometer) cardiac output (Modelflow), muscle and cerebral oxygenation (near-infrared spectroscopy), and middle cerebral artery blood flow velocity (MCAV; transcranial Doppler ultrasound) were measured continuously. The effect of hypoxia on dynamic cerebral autoregulation was assessed with transfer function gain and phase shift in mean BP and MCAV. At rest, hypoxia resulted in increases in ventilation, progressive hypocapnia, and general sympathoexcitation (i.e., elevated HR and cardiac output); these responses were more marked during hypoxic exercise (P < 0.05 vs. rest) and were also reflected in elevation of the slopes of the linear regressions of ventilation, HR, and cardiac output with Sa(O(2)) (P < 0.05 vs. rest). MCAV was maintained during hypoxic exercise, despite marked hypocapnia (44.1 +/- 2.9 to 36.3 +/- 4.2 Torr; P < 0.05). Conversely, hypoxia both at rest and during exercise decreased cerebral oxygenation compared with muscle. The low-frequency phase between MCAV and mean BP was lowered during hypoxic exercise, indicating impairment in cerebral autoregulation. These data indicate that increases in cerebral neurogenic activity and/or sympathoexcitation during hypoxic exercise can potentially outbalance the hypocapnia-induced lowering of MCAV. Despite maintaining MCAV, such hypoxic exercise can potentially compromise cerebral autoregulation and oxygenation.     

Alterations in cerebral dynamics at high altitude following partial acclimatization in humans: wakefulness and sleep.

We tested the hypothesis that, following exposure to high altitude, cerebrovascular reactivity to CO2 and cerebral autoregulation would be attenuated. Such alterations may predispose to central sleep apnea at high altitude by promoting changes in brain PCO2 and thus breathing stability. We measured middle cerebral artery blood flow velocity (MCAv; transcranial Doppler ultrasound) and arterial blood pressure during wakefulness in conditions of eucapnia (room air), hypocapnia (voluntary hyperventilation), and hypercapnia (isooxic rebeathing), and also during non-rapid eye movement (stage 2) sleep at low altitude (1,400 m) and at high altitude (3,840 m) in five individuals. At each altitude, sleep was studied using full polysomnography, and resting arterial blood gases were obtained. During wakefulness and polysomnographic-monitored sleep, dynamic cerebral autoregulation and steady-state changes in MCAv in relation to changes in blood pressure were evaluated using transfer function analysis. High altitude was associated with an increase in central sleep apnea index (0.2 +/- 0.4 to 20.7 +/- 23.2 per hour) and an increase in mean blood pressure and cerebrovascular resistance during wakefulness and sleep. MCAv was unchanged during wakefulness, whereas there was a greater decrease during sleep at high altitude compared with low altitude (-9.1 +/- 1.7 vs. -4.8 +/- 0.7 cm/s; P < 0.05). At high altitude, compared with low altitude, the cerebrovascular reactivity to CO2 in the hypercapnic range was unchanged (5.5 +/- 0.7 vs. 5.3 +/- 0.7%/mmHg; P = 0.06), while it was lowered in the hypocapnic range (3.1 +/- 0.7 vs. 1.9 +/- 0.6%/mmHg; P < 0.05). Dynamic cerebral autoregulation was further reduced during sleep (P < 0.05 vs. low altitude). Lowered cerebrovascular reactivity to CO2 and reduction in both dynamic cerebral autoregulation and MCAv during sleep at high altitude may be factors in the pathogenesis of breathing instability.     

Cerebral hypoperfusion during hypoxic exercise following two different hypoxic exposures: independence from changes in dynamic autoregulation and reactivity

We examined the effects of exposure to 10-12 days intermittent hypercapnia [IHC: 5:5-min hypercapnia (inspired fraction of CO(2) 0.05)-to-normoxia for 90 min (n = 10)], intermittent hypoxia [IH: 5:5-min hypoxia-to-normoxia for 90 min (n = 11)] or 12 days of continuous hypoxia [CH: 1,560 m (n = 7)], or both IH followed by CH on cardiorespiratory and cerebrovascular function during steady-state cycling exercise with and without hypoxia (inspired fraction of oxygen, 0.14). Cerebrovascular reactivity to CO(2) was also monitored. During all procedures, ventilation, end-tidal gases, blood pressure, muscle and cerebral oxygenation (near-infrared spectroscopy), and middle cerebral artery blood flow velocity (MCAv) were measured continuously. Dynamic cerebral autoregulation (CA) was assessed using transfer-function analysis. Hypoxic exercise resulted in increases in ventilation, hypocapnia, heart rate, and cardiac output when compared with normoxic exercise (P < 0.05); these responses were unchanged following IHC but were elevated following the IH and CH exposure (P < 0.05) with no between-intervention differences. Following IH and/or CH exposure, the greater hypocapnia during hypoxic exercise provoked a decrease in MCAv (P < 0.05 vs. preexposure) that was related to lowered cerebral oxygenation (r = 0.54; P < 0.05). Following any intervention, during hypoxic exercise, the apparent impairment in CA, reflected in lowered low-frequency phase between MCAv and BP, and MCAv-CO(2) reactivity, were unaltered. Conversely, during hypoxic exercise following both IH and/or CH, there was less of a decrease in muscle oxygenation (P < 0.05 vs. preexposure). Thus IH or CH induces some adaptation at the muscle level and lowers MCAv and cerebral oxygenation during hypoxic exercise, potentially mediated by the greater hypocapnia, rather than a compromise in CA or MCAv reactivity.     

Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit?

Occupational or recreational exercise reduces mortality from cardiovascular disease. The potential mechanisms for this reduction may include changes in blood pressure (BP) and autonomic control of the circulation. Therefore, we conducted the present long-term longitudinal study to quantify the dose-response relationship between the volume and intensity of exercise training, and regulation of heart rate (HR) and BP. We measured steady-state hemodynamics and analyzed dynamic cardiovascular regulation by spectral and transfer function analysis of cardiovascular variability in 11 initially sedentary subjects during 1 yr of progressive endurance training sufficient to allow them to complete a marathon. From this, we found that 1) moderate exercise training for 3 mo decreased BP, HR, and total peripheral resistance, and increased cardiovascular variability and arterial baroreflex sensitivity; 2) more prolonged and intense training did not augment these changes further; and 3) most of these changes returned to control values at 12 mo despite markedly increased training duration and intensity equivalent to that routinely observed in competitive athletes. In conclusion, increases in R-wave-R-wave interval and cardiovascular variability indexes are consistent with an augmentation of vagal modulation of HR after exercise training. It appears that moderate doses of training for 3 mo are sufficient to achieve this response as well as a modest hypotensive effect from decreasing vascular resistance. However, more prolonged and intense training does not necessarily lead to greater enhancement of circulatory control and, therefore, may not provide an added protective benefit via autonomic mechanisms against death by cardiovascular disease.     

Human cardiorespiratory and cerebrovascular function during severe passive hyperthermia: effects of mild hypohydration.

The influence of severe passive heat stress and hypohydration (Hypo) on cardiorespiratory and cerebrovascular function is not known. We hypothesized that 1) heating-induced hypocapnia and peripheral redistribution of cardiac output (Q) would compromise blood flow velocity in the middle cerebral artery (MCAv) and cerebral oxygenation; 2) Hypo would exacerbate the hyperthermic-induced hypocapnia, further decreasing MCAv; and 3) heating would reduce MCAv-CO2 reactivity, thereby altering ventilation. Ten men, resting supine in a water-perfused suit, underwent progressive hyperthermia [0.5 degrees C increments in core (esophageal) temperature (TC) to +2 degrees C] while euhydrated (Euh) or Hypo by 1.5% body mass (attained previous evening). Time-control (i.e., non-heat stressed) data were obtained on six of these subjects. Cerebral oxygenation (near-infrared spectroscopy), MCAv, end-tidal carbon dioxide (PetCO2) and arterial blood pressure, Q (flow model), and brachial and carotid blood flows (CCA) were measured continuously each 0.5 degrees C change in TC. At each level, hypercapnia was achieved through 3-min administrations of 5% CO2, and hypocapnia was achieved with controlled hyperventilation. At baseline in Hypo, heart rate, MCAv and CCA were elevated (P<0.05 vs. Euh). MCAv-CO2 reactivity was unchanged in both groups at all TC levels. Independent of hydration, hyperthermic-induced hyperventilation caused a severe drop in PetCO2 (-8+/-1 mmHg/ degrees C), which was related to lower MCAv (-15+/-3%/ degrees C; R2=0.98; P<0.001). Elevations in Q were related to increases in brachial blood flow (R2=0.65; P<0.01) and reductions in MCAv (R2=0.70; P<0.01), reflecting peripheral distribution of Q. Cerebral oxygenation was maintained, presumably via enhanced O2-extraction or regional differences in cerebral perfusion.     

Age-dependent relationship between the carotid intima-media thickness, baroreflex sensitivity, and the inter-beat interval in normotensive and hypertensive subjects

The interrelationship between baroreflex sensitivity expressed in ms/mm Hg (BRS) or in Hz/mm Hg (BRSf), carotid wall thickness (IMT), and age was investigated in hypertensive and normotensive subjects with respect to the mean inter-beat interval (IBI) and blood pressure (BP). BP monitoring was performed in 25 treated hypertensives (Hy; 47.4+/-9.2 years of age) and 23 normotensives (Norm; 44.5+/-8.1 years). IMT was measured by ultrasonography. BRS and BRSf were determined by the spectral method (five-minute non-invasive beat-to-beat recording of BP and IBI, Finapres, controlled breathing at a frequency of 0.33 Hz). Significant differences between Hy and Norm were detected in IMT (Hy: 0.624+/-0.183, Norm: 0.522+/-0.070 mm; p<0.01), BRS (Hy: 3.5+/-1.6, Norm: 5.7+/-2.3 ms/mm Hg; p<0.01), BRSf (Hy: 0.005+/-0.002, Norm: 0.009+/-0.004 Hz/mm Hg; p<0.01), systolic BP (Hy: 131+/-21, Norm: 116+/-17 mm Hg; p<0.01) and diastolic BP (Hy: 77+/-16, Norm: 64+/-12 mm Hg; p<0.01). A significant correlation was found between age and IMT (Norm: 0.523, p<0.05; Hy+Norm: 0.419, p<0.01), age and BRS (Norm: -0.596, p< 0.01; Hy+Norm: -0.496, p<0.01), age and BRSf (Norm: -0.555, p<0.01; Hy: -0.540, p <0.01; Hy+Norm: -0.627, p<0.01), age and IBI (Hy: 0.478, p<0.05), age and diastolic BP (Hy: -0.454, p<0.05), BRS and IMT (Hy+Norm: -0.327, p<0.05) and BRSf and IMT (Hy+Norm: -0.358, p<0.05). Hypertensive patients have increased IMT and decreased BRS and BRSf. The positive correlation between age and IMT and the negative correlation between age and BRS and BRSf are in agreement with the hypothesis that the age-dependent decrease of baroreflex sensitivity corresponds to the age-related structural changes of the carotid wall. Using two indices of baroreflex sensitivity, BRS and BRSf, we could show that baroreflex sensitivity in hypertensives is lower not only due to thickening of the carotid wall, but also due to aging.     

Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation: alterations with hyperoxia.

We hypothesized that 1) acute severe hypoxia, but not hyperoxia, at sea level would impair dynamic cerebral autoregulation (CA); 2) impairment in CA at high altitude (HA) would be partly restored with hyperoxia; and 3) hyperoxia at HA and would have more influence on blood pressure (BP) and less influence on middle cerebral artery blood flow velocity (MCAv). In healthy volunteers, BP and MCAv were measured continuously during normoxia and in acute hypoxia (inspired O2 fraction = 0.12 and 0.10, respectively; n = 10) or hyperoxia (inspired O2 fraction, 1.0; n = 12). Dynamic CA was assessed using transfer-function gain, phase, and coherence between mean BP and MCAv. Arterial blood gases were also obtained. In matched volunteers, the same variables were measured during air breathing and hyperoxia at low altitude (LA; 1,400 m) and after 1-2 days after arrival at HA ( approximately 5,400 m, n = 10). In acute hypoxia and hyperoxia, BP was unchanged whereas it was decreased during hyperoxia at HA (-11 +/- 4%; P < 0.05 vs. LA). MCAv was unchanged during acute hypoxia and at HA; however, acute hyperoxia caused MCAv to fall to a greater extent than at HA (-12 +/- 3 vs. -5 +/- 4%, respectively; P < 0.05). Whereas CA was unchanged in hyperoxia, gain in the low-frequency range was reduced during acute hypoxia, indicating improvement in CA. In contrast, HA was associated with elevations in transfer-function gain in the very low- and low-frequency range, indicating CA impairment; hyperoxia lowered these elevations by approximately 50% (P < 0.05). Findings indicate that hyperoxia at HA can partially improve CA and lower BP, with little effect on MCAv.     

Autonomic control of the respiratory-hemodynamic system in 8-to 11-year-old children with different baroreflex sensitivities

The efficiency of baroreflex control depends on the baroreflex sensitivity (BRS), which is defined as the ratio of the change in the heart rate (HR) to the change in the blood pressure (BP). The BRS value may be used for assessing the autonomic control of the cardiovascular system and the degree of autonomic dysfunction. Until recently, the baroreflex had not been assessed in a large population of healthy subjects. In this study, the BRS was estimated by the ratio of the low-frequency component of the HR spectrum and the low-frequency component of the rhythm of the systolic BP. For assessing the arterial baroreflex in children, the BRSs for spontaneous and induced baroreflexes were compared. Sex-and age-related differences in BRS were found in 8-to-11-year-old children, and correlations between BRS and some spectral components of HR variability (HRV) and BP rhythm variability were determined. Cluster analysis of the BRS calculated for the spontaneous baroreflex at rest was used to distinguish three clusters of subjects (with high, medium, and low BRSs). These clusters differed in the variability of the basic parameter and size and showed sex-related differences.     

Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients.

The arterial baroreflex buffers slow (<0.05 Hz) blood pressure (BP) fluctuations, mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an important characteristic of baroreflex control, is often noninvasively assessed by relating heart rate (HR) fluctuations to BP fluctuations; more specifically, spectral BRS assessment techniques focus on the BP-to-HR transfer function around 0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated BP buffering is based on two considerations: 1) baroreflex-modulated peripheral vasomotor function is not necessarily related to baroreflex-HR transfer; and 2) although BP fluctuations around 0.1 Hz (Mayer waves) might be related to baroreflex BP buffering, they are merely a not-intended side effect of a closed-loop control system. To further investigate the relationship between BRS and baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP control to simulate normal subjects and heart failure patients. Output variables for various randomly chosen combinations of feedback gains in the baroreflex arms were BP resonance, BP-buffering capacity, and BRS. Our results show that BP buffering and BP resonance are related expressions of baroreflex BP control and depend strongly on the sympathetic gain to the peripheral resistance. BRS is almost uniquely determined by the vagal baroreflex gain to the sinus node. In conclusion, BP buffering and BRS are unrelated unless coupled gains in all baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most likely to be attributed to vagal effects on the heart instead of to effective BP buffering.     

Autonomic Recovery Is Delayed in Chinese Compared with Caucasian following Treadmill Exercise

Caucasian populations have a higher prevalence of cardiovascular disease (CVD) when compared with their Chinese counterparts and CVD is associated with autonomic function. It is unknown whether autonomic function during exercise recovery differs between Caucasians and Chinese. The present study investigated autonomic recovery following an acute bout of treadmill exercise in healthy Caucasians and Chinese. Sixty-two participants (30 Caucasian and 32 Chinese, 50% male) performed an acute bout of treadmill exercise at 70% of heart rate reserve. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were obtained during 5-min epochs at pre-exercise, 30-min, and 60-min post-exercise. HRV was assessed using frequency [natural logarithm of high (LnHF) and low frequency (LnLF) powers, normalized high (nHF) and low frequency (nLF) powers, and LF/HF ratio] and time domains [Root mean square of successive differences (RMSSD), natural logarithm of RMSSD (LnRMSSD) and R–R interval (RRI)]. Spontaneous BRS included both up-up and down-down sequences. At pre-exercise, no group differences were observed for any HR, HRV and BRS parameters. During exercise recovery, significant race-by-time interactions were observed for LnHF, nHF, nLF, LF/HF, LnRMSSD, RRI, HR, and BRS (up-up). The declines in LnHF, nHF, RMSSD, RRI and BRS (up-up) and the increases in LF/HF, nLF and HR were blunted in Chinese when compared to Caucasians from pre-exercise to 30-min to 60-min post-exercise. Chinese exhibited delayed autonomic recovery following an acute bout of treadmill exercise. This delayed autonomic recovery may result from greater sympathetic dominance and extended vagal withdrawal in Chinese.Trial Registration: Chinese Clinical Trial Register ChiCTR-IPR-15006684     

Cardiovascular Autonomic Regulation,ETCO2 and the Heart Rate Response to the Tilt Table Test in Patients with Orthostatic Intolerance

Chronic orthostatic intolerance (COI) is defined by changes in heart rate (HR), blood pressure (BP), respiration, symptoms of cerebral hypoperfusion and sympathetic overactivation. Postural tachycardia syndrome (POTS) is the most common form of COI in young adults and is defined by an orthostatic increase in heart rate (HR) of?≥?30 bpm in the absence of orthostatic hypotension. However, some patients referred for evaluation of COI symptoms do not meet the orthostatic HR response criterion of POTS despite debilitating symptoms. Such patients are ill defined, posing diagnostic and therapeutic challenges. This study explored the relationship among cardiovascular autonomic control, the orthostatic HR response, EtCO₂ and the severity of orthostatic symptoms and fatigue in patients referred for evaluation of COI. Patients (N?=?108) performed standardized testing protocol of the Autonomic Reflex Screen and completed the Composite Autonomic Symptom Score (COMPASS-31) and the Fatigue Severity Scale (FSS). Greater severity of COI was associated with younger age, larger phase IV amplitude in the Valsalva maneuver and lower adrenal baroreflex sensitivity. Greater fatigue severity was associated with a larger reduction in ETCO₂ during 10 min of head-up tilt (HUT) and reduced low-frequency (LF) power of heart rate variability. This study suggests that hemodynamic changes associated with the baroreflex response and changes in EtCO₂ show a stronger association with the severity of orthostatic symptoms and fatigue than the overall orthostatic HR response in patients with COI.

     

Aldosterone impairs baroreflex sensitivity in healthy adults

Animal studies suggest that acute and chronic aldosterone administration impairs baroreceptor/baroreflex responses. We tested the hypothesis that aldosterone impairs baroreflex control of cardiac period [cardiovagal baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA, sympathetic BRS) in humans. Twenty-six young (25 +/- 1 yr old, mean +/- SE) adults were examined in this study. BRS was determined by using the modified Oxford technique (bolus infusion of nitroprusside, followed 60 s later by bolus infusion of phenylephrine) in triplicate before (Pre) and 30-min after (Post) beginning aldosterone (experimental, 12 pmol.kg(-1).min(-1); n = 10 subjects) or saline infusion (control; n = 10). BRS was quantified from the R-R interval-systolic blood pressure (BP) (cardiovagal BRS) and MSNA-diastolic BP (sympathetic BRS) relations. Aldosterone infusion increased serum aldosterone levels approximately fourfold (P < 0.05) and decreased (P < 0.05) cardiovagal (19.0 +/- 2.3 vs. 15.6 +/- 1.7 ms/mmHg Pre and Post, respectively) and sympathetic BRS [-4.4 +/- 0.4 vs. -3.0 +/- 0.4 arbitrary units (AU).beat(-1).mmHg(-1)]. In contrast, neither cardiovagal (19.3 +/- 3.3 vs. 20.2 +/- 3.3 ms/mmHg) nor sympathetic BRS (-3.8 +/- 0.5 vs. -3.6 +/- 0.5 AU.beat(-1).mmHg(-1)) were altered (Pre vs. Post) in the control group. BP, heart rate, and MSNA at rest were similar in experimental and control subjects before and after the intervention. Additionally, neural and cardiovascular responses to a cold pressor test and isometric handgrip to fatigue were unaffected by aldosterone infusion (n = 6 subjects). These data provide direct experimental support for the concept that aldosterone impairs baroreflex function (cardiovagal and sympathetic BRS) in humans. Therefore, aldosterone may be an important determinant/modulator of baroreflex function in humans.     

Chronic central leptin infusion restores cardiac sympathetic-vagal balance and baroreflex sensitivity in diabetic rats

This study tested whether leptin restores sympathetic-vagal balance, heart rate (HR) variability, and cardiac baroreflex sensitivity (BRS) in streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were instrumented with arterial and venous catheters, and a cannula was placed in the lateral ventricle for intracerebroventricular (ICV) leptin infusion. Blood pressure (BP) and HR were monitored by telemetry. BRS and HR variability were estimated by linear regression between HR and BP responses to phenylephrine or sodium nitroprusside and autoregressive spectral analysis. Measurements were made during control period, 7 days after induction of diabetes, and 7 days after ICV leptin infusion. STZ diabetes was associated with hyperglycemia (422 +/- 17 mg/dl) and bradycardia (-79 +/- 4 beats/min). Leptin decreased glucose levels (165 +/- 16 mg/dl) and raised HR to control values (303 +/- 10 to 389 +/- 10 beats/min). Intrinsic HR (IHR) and chronotropic responses to a full-blocking dose of propranolol and atropine were reduced during diabetes (260 +/- 7 vs. 316 +/- 6, -19 +/- 2 vs. -43 +/- 6, and 39 +/- 3 vs. 68 +/- 8 beats/min), and leptin treatment restored these variables to normal (300 +/- 7, -68 +/- 10, and 71 +/- 8 beats/min). Leptin normalized BRS (bradycardia, -2.6 +/- 0.3, -1.7 +/- 0.2, and -3.0 +/- 0.5; and tachycardia, -3.2 +/- 0.4, -1.9 +/- 0.3, and -3.4 +/- 0.3 beats.min(-1).mmHg(-1) for control, diabetes, and leptin) and HR variability (23 +/- 4 to 11 +/- 1.5 ms2). Chronic glucose infusion to maintain hyperglycemia during leptin infusion did not alter the effect of leptin on IHR but abolished the improved BRS. These results show rapid impairment of autonomic nervous system control of HR after the induction of diabetes and that central nervous system actions of leptin can abolish the hyperglycemia as well as the altered IHR and BRS in STZ-induced diabetes.     

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.