Increased sympathetic and decreased parasympathetic cardiovascular modulation in normal humans with acute sleep deprivation.

Cardiovascular autonomic modulation during 36 h of total sleep deprivation (SD) was assessed in 18 normal subjects (16 men, 2 women, 26.0 +/- 4.6 yr old). ECG and continuous blood pressure (BP) from radial artery tonometry were obtained at 2100 on the first study night (baseline) and every subsequent 12 h of SD. Each measurement period included resting supine, seated, and seated performing computerized tasks and measured vigilance and executive function. Subjects were not supine in the periods between measurements. Spectral analysis of heart rate variability (HRV) and BP variability (BPV) was computed for cardiac parasympathetic modulation [high-frequency power (HF)], sympathetic modulation [low-frequency power (LF)], sympathovagal balance (LF/HF power of R-R variability), and BPV sympathetic modulation (at LF). All spectral data were expressed in normalized units [(total power of the components/total power-very LF) x 100]. Spontaneous baroreflex sensitivity (BRS), based on systolic BP and pulse interval powers, was also measured. Supine and sitting, BPV LF was significantly increased from baseline at 12, 24, and 36 h of SD. Sitting, HRV LF was increased at 12 and 24 h of SD, HRV HF was decreased at 12 h SD, and HRV LF/HF power of R-R variability was increased at 12 h of SD. BRS was decreased at 24 h of SD supine and seated. During the simple reaction time task (vigilance testing), the significantly increased sympathetic and decreased parasympathetic cardiac modulation and BRS extended through 36 h of SD. In summary, acute SD was associated with increased sympathetic and decreased parasympathetic cardiovascular modulation and decreased BRS, most consistently in the seated position and during simple reaction-time testing.     

Age dependency of cardiovascular autonomic responses to head-up tilt in healthy subjects.

In elderly subjects, heart rate responses to postural change are attenuated, whereas their vascular responses are augmented. Altered strategy in maintaining blood pressure homeostasis during upright position may result from various cardiovascular changes, including age-related cardiovascular autonomic dysfunction. This exploratory study was conducted to evaluate impact of age on cardiovascular autonomic responses to head-up tilt (HUT) in healthy subjects covering a wide age range. The study population consisted of 63 healthy, normal-weight, nonsmoking subjects aged 23-77 yr. Five-minute electrocardiogram and finger blood pressure recordings were performed in the supine position and in the upright position 5 min after 70 degrees HUT. Stroke volume was assessed from noninvasive blood pressure signals by the arterial pulse contour method. Heart rate variability (HRV) and systolic blood pressure variability (SBPV) were analyzed by using spectral analysis, and baroreflex sensitivity (BRS) was assessed by using sequence and cross-spectral methods. Cardiovascular autonomic activation during HUT consisted of decreases in HRV and BRS and an increase in SBPV. These changes became attenuated with aging. Age correlated significantly with amplitude of HUT-stimulated response of the high-frequency component (r = -0.61, P < 0.001) and the ratio of low-frequency to high-frequency power of HRV (r = -0.31, P < 0.05) and indexes of BRS (local BRS: r = -0.62, P < 0.001; cross-spectral baroreflex sensitivity in the low-frequency range: r = -0.38, P < 0.01). Blood pressure in the upright position was maintained well irrespective of age. However, the HUT-induced increase in heart rate was more pronounced in the younger subjects, whereas the increase in peripheral resistance was predominantly observed in the older subjects. Thus it is likely that whereas the dynamic capacity of cardiac autonomic regulation decreases, vascular responses related to vasoactive mechanisms and vascular sympathetic regulation become augmented with increasing age.     

Age dependency and correlation of heart rate variability,blood pressure variability and baroreflex sensitivity

Simultaneous analysis of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) with different types of measures may provide non-duplicative information about autonomic cardiovascular regulation. Therefore, a multiple signal analysis of cardiovascular time series will enhance the physiological understanding of neuro cardiovascular regulation with deconditioning in bedrest or related gravitational physiological studies. It has been shown that age is an important determinant of HRV and BRS in healthy subjects. Whereas in the case of BPV, the effect of aging seems to depend upon the activity status of the subjects. In view of the facts that most of the previous works were dealing with only the variability of one kind of cardiovascular parameters in one study with conventional time-domain and/or frequency-domain analysis, we therefore designed the present work to compare the HRV, BPV and BRS between young and middle-aged male healthy subjects in one study with the same subjects using various techniques, including the approximate entropy (ApEn) measurement, a statistic quantifying HRV "complexity" derived from non-linear dynamics.     

Mechanisms of blood pressure and heart rate variability: an insight from low-level paraplegia

It is still unclear whether the low-frequency oscillation in heart rate is generated by an endogenous neural oscillator or by a baroreflex resonance. Our aim was to investigate this issue by analyzing blood pressure and heart rate variability and the baroreflex function in paraplegic subjects with spinal cord injury below the fourth thoracic vertebra. These subjects were selected because they represent a model of intact central neural drive to the heart, with a partially impaired autonomic control of the vessels. In our study, arterial blood pressure and ECG were recorded in 33 able-bodied controls and in 33 subjects with spinal cord lesions between the fifth thoracic and the fourth lumbar vertebra 1) during supine rest (lowest sympathetic activation), 2) sitting on a wheelchair (light sympathetic activation), and 3) during exercise (moderate sympathetic activation). Blood pressure and heart rate spectra, coherence, and baroreflex function (sequence technique) were estimated in each condition. Compared with controls, paraplegic subjects showed a reduction of the low-frequency power of blood pressure and heart rate, and, unlike controls, a 0.1-Hz peak did not appear in their spectra. Sympathetic activation increased the 0.1-Hz peak of blood pressure and heart rate and the coherence at 0.1 Hz in controls only. Paraplegic subjects also had significantly lower baroreflex effectiveness and greater blood pressure variability. In conclusion, the disappearance of the 10-s oscillation of heart rate and blood pressure in subjects with spinal cord lesion supports the hypothesis of the baroreflex nature of this phenomenon.     

Autonomic cardiac control in animal models of cardiovascular diseases II. Variability analysis in transgenic rats with alpha-tropomyosin mutations Asp175Asn and Glu180Gly.

Animal models of cardiovascular diseases allow to investigate relevant pathogenetic mechanisms in detail. In the present study, the mutations Asp175Asn and Glu180Gly in alpha-tropomyosin (TPM1), known cause familiar hypertrophic cardiomyopathy (FHC) were studied for changes in hemodynamic parameters and spontaneous baroreflex regulation in transgenic rats in comparison to transgenic and non-transgenic controls by telemetry. Heart rate variability (HRV) and blood pressure variability (BPV) were analyzed using time- and frequency domain, as well as non-linear measures. The dual sequence method was used for the estimation of the baroreflex regulation. In transgenic rats harboring mutated TPM1, changes in HRV were detected during exercise, but not at rest. Both mutations, Asp175Asn and Glu180Gly, caused increased low frequency power. In addition, in animals with mutation Asp175Asn a reduced total HRV was observed. BPV did not show any differences between all transgenic animal lines. During exercise, a strong increase in the number of bradycardic and tachycardic fluctuations accompanied with decreased baroreflex sensitivity (BRS) was detected in animals with either TPM1 mutation, Asp175Asn or Glu180Gly. These data suggest, that the analysis of cardiac autonomic control, particularly of baroreflex regulation, represents a powerful non-invasive approach to investigate the effects of subtle changes in sarcomeric architecture on cardiac physiology in vivo. In case of mutations Asp175Asn or Glu180Gly in TPM1, early detection of alterations in autonomic cardiac control could help to prevent sudden cardiac death in affected persons.     

Sex differences in baroreflex sensitivity, heart rate variability, and end organ damage in the TGR(mRen2)27 rat

The aim of this investigation was to evaluate sex differences in baroreflex and heart rate variability (HRV) dysfunction and indexes of end-organ damage in the TG(mRen2)27 (Ren2) rat, a model of renin overexpression and tissue renin-angiotensin-aldosterone system overactivation. Blood pressure (via telemetric monitoring), blood pressure variability [BPV; SD of systolic blood pressure (SBP)], spontaneous baroreflex sensitivity, HRV [HRV Triangular Index (HRV-TI), standard deviation of the average NN interval (SDNN), low and high frequency power (LF and HF, respectively), and Poincaré plot analysis (SD1, SD2)], and cardiovascular function (pressure-volume loop analysis and proteinuria) were evaluated in male and female 10-wk-old Ren2 and Sprague Dawley rats. The severity of hypertension was greater in Ren2 males (R2-M) than in Ren2 females (R2-F). Increased BPV, suppression of baroreflex gain, decreased HRV, and associated end-organ damage manifested as cardiac dysfunction, myocardial remodeling, elevated proteinuria, and tissue oxidative stress were more pronounced in R2-M compared with R2-F. During the dark cycle, HRV-TI and SDNN were negatively correlated with SBP within R2-M and positively correlated within R2-F; within R2-M, these indexes were also negatively correlated with end-organ damage [left ventricular hypertrophy (LVH)]. Furthermore, within R2-M only, LVH was strongly correlated with indexes of HRV representing predominantly vagal (HF, SD1), but not sympathetic (LF, SD2), variability. These data demonstrated relative protection in females from autonomic dysfunction and end-organ damage associated with elevated blood pressure in the Ren2 model of hypertension.     

Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes.

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.     

Functional characteristics of the cardiovascular system in adolescents with high normal blood pressure

Sanogenetic monitoring of schoolchildren’s health has demonstrated that, among high school students, the proportion of adolescents with elevated blood pressure (hypertension + hypernormotension) has risen from 15–20% in 8th-year students to 30–50% in 9th- to 11th-year students, while the proportion of adolescents with hypertension was 3.7% in all age groups. The level of blood pressure (BP) was compared with parameters of the autonomic control of the cardiovascular system. A high normal BP in adolescents 13–14 and 17–18 years of age was correlated with the higher proportion of low frequencies in the spectrum of heart rate variability (HRV) and with the lower sensitivity of the arterial baroreflex. At the age of 15–16 years, a high normal BP was accompanied by a reduced heart rate and a higher sensitivity of the arterial baroreflex; BP correlated also with a decrease in power of the high-frequency region of the HRV spectrum. Unlike normotensive age-matched subjects, hypernormotensive adolescents 15–16 years of age have a lower finger blood pressure and reduced relative power of the low-frequency range in the HRV spectrum during the functional test (an increase in the dead space). This may be a result of a functional inadaptability of sympathetic autonomic regulation.     

Impaired cardiac and sympathetic autonomic control in rats differing in acetylcholine receptor sensitivity

Acetylcholine receptors (AChR) are important in premotor and efferent control of autonomic function; however, the extent to which cardiovascular function is affected by genetic variations in AChR sensitivity is unknown. We assessed heart rate variability (HRV) and baroreflex sensitivity (BRS) in rats bred for resistance (FRL) or sensitivity (FSL) to cholinergic agents compared with Sprague-Dawley rats (SD), confirmed by using hypothermic responses evoked by the muscarinic agonist oxotremorine (0.2 mg/kg i.p.) (n > or = 9 rats/group). Arterial pressure, ECG, and splanchnic sympathetic (SNA) and phrenic (PNA) nerve activities were acquired under anesthesia (urethane 1.3 g/kg i.p.). HRV was assessed in time and frequency domains from short-term R-R interval data, and spontaneous heart rate BRS was obtained by using a sequence method at rest and after administration of atropine methylnitrate (mATR, 2 mg/kg i.v.). Heart rate and SNA baroreflex gains were assessed by using conventional pharmacological methods. FRL and FSL were normotensive but displayed elevated heart rates, reduced HRV and HF power, and spontaneous BRS compared with SD. mATR had no effect on these parameters in FRL or FSL, indicating reduced cardiovagal tone. FSL exhibited reduced PNA frequency, longer baroreflex latency, and reduced baroreflex gain of heart rate and SNA compared with FRL and SD, indicating in FSL dual impairment of cardiac and circulatory baroreflexes. These findings show that AChR resistance results in reduced cardiac muscarinic receptor function leading to cardiovagal insufficiency. In contrast, AChR sensitivity results in autonomic and respiratory abnormalities arising from alterations in central muscarinic and or other neurotransmitter receptors.     

Heart rate variability and spontaneous baroreflex sequences in supine healthy volunteers subjected to nasal positive airway pressure.

To determine the dynamic effects of short-term nasal positive airway pressure (nPAP) on cardiovascular autonomic control, continuous recordings of noninvasively obtained hemodynamic measurements and heart rate variability (HRV) were obtained in 10 healthy subjects during frequency-controlled breathing (between 0.20 and 0.24 Hz) in supine posture under different pressures of nPAP ranging from 3 to 20 cmH(2)O. HRV was assessed using spectral analysis of the R-R interval. The slope of the regression line between spontaneous systolic blood pressure and pulse interval changes was taken as an index of the sensitivity of arterial baroreflex modulation of heart rate (sequence method). Application of nPAP resulted in a pressure-dependent decrease of cardiac output and stroke volume (P < 0.05, ANOVA) and in an increase in total peripheral resistance (P < 0.03, ANOVA). Hemodynamic changes under increasing nPAP were accompanied by a decrease in total power of HRV despite mean R-R interval remaining unchanged. The overall decrease in HRV was accompanied by a reduction across all frequency bands when absolute units were used (P < 0.01). When the power of low frequency and high frequency was calculated in normalized units, a diminished high frequency and an increased low-to-high frequency ratio were observed (P < 0.05). Compared with low levels of nPAP, pressure levels of >10 cmH(2)O were associated with a significant decline in the mean slope of spontaneous baroreceptor sequences (P < 0.04). These findings indicate that short-term administration of nPAP in normal subjects exerts significant alterations in R-R interval variability and spontaneous baroreflex modulation of heart rate.     

Autonomic nervous nonlinear interactions lead to frequency modulation between low- and high-frequency bands of the heart rate variability spectrum

Cardiac sympathetic and parasympathetic neural activities have been found to interact with each other to efficiently regulate the heart rate and maintain homeostasis. Quantitative and noninvasive methods used to detect the presence of interactions have been lacking, however. This may be because interactions among autonomic nervous systems are nonlinear and nonstationary. The goal of this work was to identify nonlinear interactions between the sympathetic and parasympathetic nervous systems in the form of frequency and amplitude modulations in human heart rate data. To this end, wavelet analysis was performed, followed by frequency analysis of the resultant wavelet decomposed signals in several frequency brackets defined as very low frequency (f < 0.04 Hz), low frequency (LF; 0.04-0.15 Hz), and high frequency (HF; 0.15-0.4 Hz). Our analysis suggests that the HF band is significantly modulated by the LF band in the heart rate data obtained in both supine and upright body positions. The strength of modulations is stronger in the upright than supine position, which is consistent with elevated sympathetic nervous activities in the upright position. Furthermore, significantly stronger frequency modulation than in the control condition was also observed with the cold pressor test. The results with the cold pressor test, as well as the body position experiments, further demonstrate that the frequency modulation between LF and HF is most likely due to sympathetic and parasympathetic nervous interactions during sympathetic activations. The modulation phenomenon suggests that the parasympathetic nervous system is frequency modulated by the sympathetic nervous system. In this study, there was no evidence of amplitude modulation among these frequencies.     

Effects of corticospinal tract stimulation on renal sympathetic nerve activity in rats with intact and chronically lesioned spinal cords

Sympathetic preganglionic neurons and interneurons are closely apposed (presumably synapsed upon) by corticospinal tract (CST) axons. Sprouting of the thoracic CST rostral to lumbar spinal cord injuries (SCI) substantially increases the incidence of these appositions. To test our hypothesis that these additional synapses would increase CST control of sympathetic activity after SCI, we measured the effects of electrical stimulation of the CST on renal sympathetic nerve activity (RSNA) and arterial pressure (AP) in alpha-chloralose-anesthetized rats with either chronically intact or chronically lesioned spinal cords. Stimuli were delivered to the CST at intensities between 25-150 muA and frequencies between 25 and 75 Hz. Stimulation of the CST at the midcervical level decreased RSNA and AP. These decreases were not mediated by direct projections of the CST to the thoracic spinal cord because we could still elicit them by midcervical stimulation after acute lesions of the CST at caudal cervical levels. In contrast, caudal thoracic CST stimulation increased RSNA and AP. Neither the responses to cervical nor thoracic stimulation were affected by chronic lumbar SCI. These data show that the CST mediates decreases in RSNA via a cervical spinal system but excites spinal sympathetic neurons at caudal thoracic levels. Because chronic lumber spinal cord injury affected responses evoked from neither the cervical nor thoracic CST, we conclude that lesion-induced or regeneration-induced formation of new synapses between the CST and sympathetic neurons may not affect cardiovascular regulation.     

Is Autonomic Modulation Different between European and Chinese Astronauts?

Purpose

The objective was to investigate autonomic control in groups of European and Chinese astronauts and to identify similarities and differences.

Methods

Beat-to-beat heart rate and finger blood pressure, brachial blood pressure, and respiratory frequency were measured from 10 astronauts (five European taking part in three different space missions and five Chinese astronauts taking part in two different space missions). Data recording was performed in the supine and standing positions at least 10 days before launch, and 1, 3, and 10 days after return. Cross-correlation analysis of heart rate and systolic pressure was used to assess cardiac baroreflex modulation. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic blood pressure variability.

Results

Although baseline cardiovascular parameters before spaceflight were similar in all astronauts in the supine position, a significant increase in sympathetic activity and a decrease in vagal modulation occurred in the European astronauts when standing; spaceflight resulted in a remarkable vagal decrease in European astronauts only. Similar baseline supine and standing values for heart rate, mean arterial pressure, and respiratory frequency were shown in both groups. Standing autonomic control was based on a balance of higher vagal and sympathetic modulation in European astronauts.

Conclusion

Post-spaceflight orthostatic tachycardia was observed in all European astronauts, whereas post-spaceflight orthostatic tachycardia was significantly reduced in Chinese astronauts. The basis for orthostatic intolerance is not apparent; however, many possibilities can be considered and need to be further investigated, such as genetic diversities between races, astronaut selection, training, and nutrition, etc.     

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     

Blood pressure regulation in diabetic patients with and without peripheral neuropathy

Cardiac and vascular dysfunctions resulting from autonomic neuropathy (AN) are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure (BP) regulation in patients with peripheral neuropathy and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. We continuously measured electrocardiogram, arterial BP, and respiration during supine rest and 70° head-up tilt in 12 able-bodied subjects, 7 diabetics without, 7 diabetics with possible, and 8 diabetics with definite, sensory, and/or motor neuropathy (D2). During the first 3 min of tilt, systolic BP (SBP) of D2 decreased [-10.9 ± 4.5 (SE) mmHg] but increased in able-bodied (+4.8 ± 5.4 mmHg). Compared with able-bodied, D2 had smaller low-frequency (0.04-0.15 Hz) spectral power of diastolic BP, lower baroreflex effectiveness index (BEI), and more SBP ramps. Except for low-frequency power of SBP, D2 had greater SBP and smaller RR interval harmonic and nonharmonic components at rest across the 0.003- to 0.45-Hz region. In addition, our results support previous findings of smaller HF RR interval power, smaller numbers of baroreflex sequences, and lower baroreflex sensitivity in D2. We conclude that diabetic peripheral neuropathy is accompanied by diminished parasympathetic and sympathetic control of heart rate and peripheral vasomotion and diminished baroreflex regulation. A novel finding of this study lies in the sensitivity of BEI to detect AN, presumably because of its combination of parameters that measure reductions in both sympathetic control of vasomotion and parasympathetic control of heart rate.     

A Pilot Study of the Efficacy of Heart Rate Variability (HRV) Biofeedback in Patients with Fibromyalgia

Fibromyalgia (FM) is a non-inflammatory rheumatologic disorder characterized by musculoskeletal pain, fatigue, depression, cognitive dysfunction and sleep disturbance. Research suggests that autonomic dysfunction may account for some of the symptomatology of FM. An open label trial of biofeedback training was conducted to manipulate suboptimal heart rate variability (HRV), a key marker of autonomic dysfunction. Methods: Twelve women ages 18–60 with FM completed 10 weekly sessions of HRV biofeedback. They were taught to breathe at their resonant frequency (RF) and asked to practice twice daily. At sessions 1, 10 and 3-month follow-up, physiological and questionnaire data were collected. Results: There were clinically significant decreases in depression and pain and improvement in functioning from Session 1 to a 3-month follow-up. For depression, the improvement occurred by Session 10. HRV and blood pressure variability (BPV) increased during biofeedback tasks. HRV increased from Sessions 1–10, while BPV decreased from Session 1 to the 3 month follow-up. Conclusions: These data suggest that HRV biofeedback may be a useful treatment for FM, perhaps mediated by autonomic changes. While HRV effects were immediate, blood pressure, baroreflex, and therapeutic effects were delayed. This is consistent with data on the relationship among stress, HPA axis activity, and brain function.     

Long-term bed rest-induced reductions in stroke volume during rest and exercise: cardiac dysfunction vs. volume depletion.

Long-term head-down-tilt bed rest (HDT) causes cardiovascular deconditioning, attributed to reflex dysfunctions, plasma volume reduction, or cardiac impairments. Our objective with the present study was to evaluate the functional importance and relative contribution of these during rest and exercise in supine and upright postures. We studied six subjects before (baseline), during [days 60 (D60) and 113 (D113)], and after [recovery days 0 (R0), 3 (R3), and 15 (R15)] 120 days of -6 degrees HDT. We determined cardiac output, stroke volume (SV), mean arterial pressure, and heart rate during rest and exercise in supine and upright postures. Cardiac output and SV decreased significantly in all four conditions, but the time courses differed for rest and exercise. Upright resting SV was decreased by 24 +/- 9% at D60 compared with baseline but had recovered already at R3. Supine exercise SV decreased more slowly (by 5 +/- 8% at D60 and by 18 +/- 4% at D113) and recovered more slowly after HDT termination. Steady-state mean arterial pressure showed no changes. Heart rate had increased by 18 +/- 4% at D60 and had recovered partially at R3. Our data indicate that long-term HDT causes both a rapid, preload-dependent reduction in SV, most evident during rest in the upright position, and a more slowly developing cardiac dysfunction, most evident during supine exercise. However, the ability to maintain blood pressure and to perform sustained low levels of dynamic exercise is not influenced by HDT.     

Dose-response relationship of endurance training for autonomic circulatory control in healthy seniors.

Aging results in marked abnormalities of cardiovascular regulation. Regular exercise can improve many of these age-related abnormalities. However, it remains unclear how much exercise is optimal to achieve this improvement or whether the elderly can ever improve autonomic control by exercise training to a degree similar to that observed in healthy young individuals. Ten healthy sedentary seniors [71 +/- 3 (SD) yr] trained for 12 mo; training involved progressive increases in volume and intensity. Static hemodynamics were measured, and R-wave-R-wave interval (RRI), beat-to-beat blood pressure (BP) variability, and transfer function gain between systolic BP and RRI were calculated at baseline and every 3 mo during training. Data were compared with those obtained in 12 Masters athletes (68 +/- 3 yr) and 11 healthy sedentary young individuals (29 +/- 6 yr) at baseline. Additionally, the adaptation of these variables after completion of identical training loads was compared between the seniors and the young. Indexes of RRI variability and baroreflex gain were decreased in the sedentary seniors but preserved in the Masters athletes compared with the young at baseline. With training in the seniors, baroreflex gain and resting BP showed a peak adaptation after moderate doses of training following 3-6 mo. Indexes of RRI variability continued to improve with increasing doses of training and increased to the same magnitude as the young at baseline after heavy doses of training for 12 mo; however, baroreflex gain never achieved values equivalent to the young at baseline, even after a year of training. The magnitude of the adaptation of these variables to identical training loads was similar (no interaction effects of age x training) between the seniors and the young. Thus RRI variability in seniors improves with increasing "dose" of exercise over 1 yr of training. In contrast, more moderate doses of training for 3-6 mo may optimally improve baroreflex sensitivity, associated with a modest hypotensive effect; however, higher doses of training do not lead to greater enhancement of these changes. Seniors retain a similar degree of "trainability" as young subjects for cardiac autonomic function to dynamic exercise.     

Heart rate variability responses to hypoxic and hypercapnic exposures in different mouse strains.

Heart rate variability (HRV) is a well-characterized, noninvasive means of assessing cardiac autonomic nervous system activity. This study examines the basic cardiac responses to hypoxic and hypercapnic challenges in seven strains of commonly used inbred mice (A/J, BALB/cJ, C3H/HeJ, C57BL/6J, CBA/J, DBA/2J, and FVB/J). Adult male mice, 8-12 wk of age, were chronically instrumented to a femoral artery catheter for the continuous measurement of systemic arterial blood pressure and heart rate. Mice were exposed to multiple 4-min periods of hypoxia (10% O2), hypercapnia (5% CO2), and combined hypoxia/hypercapnia (10% O2 + 5% CO2). HRV was derived from pulse intervals of the blood pressure tracings. Hypoxia induced increases in high-frequency HRV power and decreased low-frequency (LF) HRV power in most strains. Hypercapnia led to decreased high-frequency HRV power and increased LF HRV power in most strains. Strain differences were most notable in regard to the concomitant exposures of hypoxia and hypercapnia, with FVB/J mice mirroring their own response to hypercapnia alone, whereas CBA/J mice mirrored their own responses to hypoxia. As blood pressure is most likely the driving factor for heart rate changes via the baroreflex pathway, it is interesting that LF, considered to reflect cardiac sympathetic activity, was negatively correlated with heart rate, suggesting that LF changes are driven by baroreflex oscillation and not necessarily by absolute sympathetic or parasympathetic activity to the heart. These findings suggest that genetic background can influence the centrally mediated cardiovascular responses to basic hypoxic and hypercapnic challenges.     

Autonomic control after blockade of the norepinephrine transporter: a model of orthostatic intolerance.

Orthostatic intolerance is a debilitating syndrome characterized by tachycardia on assumption of upright posture. The norepinephrine (NE) transporter (NET) has been implicated in a genetic form of the disorder. We assessed the combined central and peripheral effects of pharmacological NET blockade on cardiovascular regulation and baroreflex sensitivity in rats. NE reuptake was blocked chronically in female Sprague-Dawley rats by the NET antagonist desipramine (DMI). Treated animals demonstrated an elevated supine heart rate, reduced tyramine responsiveness, and a reduced plasma ratio of the intraneuronal NE metabolite dihydroxyphenylglycol relative to NE, all of which are consistent with observations in human NET deficiency. Spectral analysis revealed a dramatic decrease in low-frequency spectral power after DMI that was consistent with decreased sympathetic outflow. Stimulation of the baroreflex with the vasodilator nitroprusside revealed an attenuated tachycardia in DMI-treated animals. This indicated that the DMI-induced sympathoinhibitory effects of increased NE in the brain stem predominates over the functional elevation of NE stimulation of peripheral targets. Thus attenuated baroreflex function and reduced sympathetic outflow may contribute to the orthostatic intolerance of severe NET deficiency.