Systolic Blood Pressure Oscillations Research Articles

The Impact of Burst Motor Cortex Stimulation on Cardiovascular Autonomic Modulation in Chronic Pain: A Feasibility Study for a New Approach to Objectively Monitor Therapeutic Effects.

Chronic refractory pain of various origin occurs in 30-45% of pain patients, and a considerable proportion remains resistant to pharmacological and behavioral therapies, requiring adjunctive neurostimulation therapies. Chronic pain is known to stimulate sympathetic outflow, yet the impact of burst motor cortex stimulation (burstMCS) on objectifiable autonomic cardiovascular parameters in chronic pain remains largely unknown. In three patients with chronic pain (2 facial pain/1 post-stroke pain), we compared pain intensity using a visual analog scale (VAS 1-10) and parameters of autonomic cardiovascular modulation at supine rest, during parasympathetic challenge with six cycles per minute of metronomic deep breathing, and during sympathetic challenge (active standing) at baseline and after 4months of burstMCS compared to age-/gender-matched healthy controls. While two out of three patients were responsive after 4months of adjunctive burstMCS (defined as pain reduction of > 30%), no differences were found in any of the three patients regarding the R-R intervals of adjacent QRS complexes (RRI, 642 vs. 676ms) and blood pressure (BP, 139/88 vs. 141/90mmHg). Under resting conditions, parameters of parasympathetic tone [normalized units of high-frequency oscillations of RRI (RRI-HFnu power) 0.24 vs. 0.38, root-mean-square differences of successive RRI (RRI-RMSSD) 7.7 vs. 14.7ms], total autonomic cardiac modulation [RRI total power 129.3 vs. 406.2ms2, standard deviation of RRI (RRI-SD) 11.6 vs. 18.5ms, coefficient of variation of RRI (RRI-CV) 1.9 vs. 3.7%], and baroreceptor reflex sensitivity (BRS, 1.9 vs. 2.3ms/mmHg) increased, and parameters of sympathetic tone [normalized units of low-frequency oscillations of RRI (RRI-LFnu power) 0.76 vs. 0.62] and sympatho-vagal balance [ratio of RR-LF to RRI-HF power (RRI-LF/HF ratio) 3.4 vs. 1.9] decreased after 4months of burstMCS. Low-frequency oscillations of systolic blood pressure (SBP-LF power), a parameter of sympathetic cardiovascular modulation, increased slightly (17.6 vs. 20.4mmHg2). During parasympathetic stimulation, the expiratory-inspiratory ratio (E/I ratio) increased slightly, while upon sympathetic stimulation, the ratio between the shortest RRI around the 15th heartbeat and the longest RRI around the 30th heartbeat after standing up (RRI 30/15 ratio) remained unchanged. Four months of adjunctive burstMCS was associated with an increase in parameters reflecting both total and parasympathetic autonomic modulation and baroreceptor reflex sensitivity. In contrast, sympathetic tone declined in our three patients, suggesting stimulation-associated improvement not only in subjectively perceived VAS pain scores, but also in objectifiable parameters of autonomic cardiovascular modulation.

A Novel Assessment of Baroreflex Activity Through the Similarity of Ternary Codes of Oscillations Between Arterial Blood Pressure and R–R Intervals

Arterial baroreflex plays a crucial role in the homeostasis of blood pressure. Elevated blood pressure stimulates baroreceptors and slows the heart rate consequently. Baroreflex activity has been quantified as the relationship between systolic blood pressure (SBP) and ECG R–R intervals (RRI), which is called baroreflex sensitivity (BRS). The purpose of this study is to define a new parameter of BRS and verify the reproducibility and validity of this indicator as compared with a popular BRS estimated by sequence method and a traditional BRS evaluated by pharmacological intervention. At first, the spontaneous oscillations of SBP and RRI were defined by ternary arithmetic codes: decrease as 0, unchanged as 1 and increase as 2. The new BRS was quantified as the similarity between these two ternary coded series after decimalization with different digits from 3 to 5. The validity and reproducibility of this method were verified in vivo in 10 adult male Wistar Kyoto rats. This new parameter correlated well with the BRS estimated by the sequence method and pharmacological intervention. The reproducibility of this novel method was good according to the Bland–Altman plot. This study offered a simple and reliable algorithm to estimate BRS, which can be embed in current instruments for clinical research.

A short set configuration attenuates the cardiac parasympathetic withdrawal after a whole-body resistance training session.

We aimed to analyse the acute effects of set configuration on cardiac parasympathetic modulation and blood pressure (BP) after a whole-body resistance training (RT) session. Thirty-two participants (23 men and 9 women) performed one control (CON) and two RT sessions differing in the set configuration but with the same intensity (15RM load), volume (200 repetitions) and total resting time (360s between sets for each exercise and 3min between exercises): a long set configuration (LSC: 4 sets of 10 repetitions with 2 resting minutes) and a short set configuration session (SSC, 8 sets of 5 repetitions with 51 resting seconds). Heart rate variability, baroreflex sensitivity, the low frequency of systolic blood pressure oscillations (LFSBP), BP and lactatemia were evaluated before and after the sessions and mechanical performance was evaluated during exercise. LSC induced greater reductions on cardiac parasympathetic modulation versus SSC after the session and the CON (p < 0.001 to p = 0.024). However, no LFSBP and BP significant changes were observed. Furthermore, LSC caused a higher lactate production (p < 0.001) and velocity loss (p ≤ 0.001) in comparison with SSC. These findings suggest that SSC attenuates the reduction of cardiac parasympathetic modulation after a whole-body RT, improving the mechanical performance and decreasing the glycolytic involvement, without alterations regarding vascular tone and BP.

Arterial Stiffness and Endothelial Function in Young Obese Patients - Vascular Resistance Matters.

Aim: Motivated by the paradoxical and differing results of the early atherosclerosis related indices – Cardio-Ankle Vascular Index (CAVI) reflecting arterial stiffness and Reactive Hyperemia Index (RHI) evaluating endothelium dependent flow-induced vasodilation – in obesity, we aimed to assess CAVI and RHI in obese adolescents and young adults in the context of differences in systemic vascular resistance (SVR).Methods: We examined 29 obese (14f, 15.4 [12.3–18.5] y; BMI: 33.2 ± 4.4 kg.m−2) and 29 non-obese gender and age matched adolescents and young adults (BMI: 21.02 ± 2.3 kg.m−2). CAVI and RHI were measured using VaSera VS-1500 (Fukuda Denshi, Japan) and Endo-PAT 2000 (Itamar Medical, Israel), respectively. Hemodynamic measures were recorded using volume-clamp plethysmography (Finometer Pro, FMS, Netherlands) and impedance cardiography (CardioScreen 2000, Medis GmbH, Germany). SVR and sympathetic activity related indices – Velocity Index (VI) and Heather Index (HI), and LFSAP (spectral power in low frequency band of systolic blood pressure oscillations) were determined.Results: In obese group, CAVI (4.59 ± 0.88 vs. 5.18 ± 0.63, p = 0.002) and its refined version CAVI0 (6.46 ± 1.39 vs. 7.33 ± 0.99, p = 0.002) were significantly lower. No significant difference in RHI was found. SVR and sympathetic activity indices were all significantly lower in the obese group than in the non-obese group. RHI correlated positively with SVR (r = 0.390, p = 0.044) in obese subjects.Conclusion: Our results indicate that both indices used for the detection of early atherosclerotic changes are influenced by vascular tone. Vascular resistance could influence CAVI and RHI results impairing their interpretation.

Childhood growth patterns and cardiovascular autonomic modulation in midlife: Northern Finland 1966 Birth Cohort Study.

To test the hypothesis that age and body mass index (BMI) at BMI peak during infancy and at BMI rebound in childhood are related to cardiovascular autonomic modulation in adulthood. At the age of 46 years, a sample (n = 5861) of the participants of the Northern Finland Birth Cohort 1966 took part in follow-up examinations. Heart rate variability (HRV), baroreflex sensitivity (BRS) and low-frequency oscillations of systolic blood pressure (LFSBP) were measured during sympathetic stimulus by standing. BMI at various ages was calculated from frequent anthropometric measurements collected from child welfare clinical records. BRS and LFSBP were available for 1243 participants with BMI peak data and 1524 participants with BMI rebound data, and HRV for 2137 participants with BMI peak data and 2688 participants with BMI rebound data. Age at BMI rebound had a significant inverse association with LFSBP (beta = -0.071, p = 0.006) after all adjustments (p < 0.001) and was also directly associated with BRS (beta = 0.082, p = 0.001) independently of birth and maternal factors (p = 0.023). BMI at BMI peak and at BMI rebound was inversely associated with high-frequency component of HRV (HF) (beta = -0.045, p = 0.036 for BMI at peak; beta = -0.043, p = 0.024 for BMI at rebound) and directly associated with the ratio of low- and high-frequency components of HRV (LF/HF ratio) (beta = 0.084, p = < 0.001 for BMI at peak; beta = 0.069, p < 0.001 for BMI at rebound). These associations remained significant after all adjustments (p < 0.05 for all). This novel study shows that younger age at BMI rebound and higher BMI at BMI peak and at BMI rebound are associated with higher levels in markers suggestive of augmented sympathetic and reduced vagal cardiovascular modulation in midlife.

Information domain analysis of respiratory sinus arrhythmia mechanisms.

Ventilation related heart rate oscillations - respiratory sinus arrhythmia (RSA) - originate in human from several mechanisms. Two most important of them - the central mechanism (direct communication between respiratory and cardiomotor centers), and the peripheral mechanism (ventilation-associated blood pressure changes transferred to heart rate via baroreflex) have been described in previous studies. The major aim of this study was to compare the importance of these mechanisms in the generation of RSA non-invasively during various states by quantifying the strength of the directed interactions between heart rate, systolic blood pressure and respiratory volume signals. Seventy-eight healthy volunteers (32 male, age range: 16.02-25.77 years, median age: 18.57 years) participated in this study. The strength of mutual interconnections among the spontaneous beat-to-beat oscillations of systolic blood pressure (SBP), R-R interval (RR signal) and respiration (volume changes - RESP signal) was quantified during supine rest, orthostatic challenge (head-up tilt, HUT) and cognitive load (mental arithmetics, MA) using bivariate and trivariate measures of cardio-respiratory information transfer to separate baroreflex and nonbaroreflex (central) mechanisms. Our results indicate that both basic mechanisms take part in RSA generation in the intact cardiorespiratory control of human subjects. During orthostatic and mental challenges baroreflex based peripheral mechanism becomes more important.

The dawn of cardiovascular neuroprosthetics: Epidural spinal cord stimulation acutely restores cardiovascular function in persons with clinically complete spinal cord injury

INTRODUCTIONNeuroprosthetic electrical stimulation of the lumbosacral spinal cord with surgical implants has the capacity to excite dormant neuronal circuitry that has lost supraspinal control due to a spinal cord injury. Very recently, this intervention was even shown to elicit involuntary and voluntary stepping‐like movement of skeletal muscles previously thought to be paralyzed.OBJECTIVEConsidering that autonomic and cardiovascular dysfunctions are the leading cause of death after spinal cord injury, and a higher health priority than walking again by these individuals, we set out to explore if lumbosacral electrical stimulation of the spinal cord could be harnessed to regulate the cardiovascular system after spinal cord injury.METHODSThree of the first individuals with cervical spinal cord injury to be implanted worldwide were assessed in the present study, all of whom presented with cardiovascular dysfunction, in the form of severe orthostatic hypotension as well as impaired cardiac and cerebral regulation. A 16‐electrode array (Fig A) paddle was implanted over the lower lumbar/sacral spinal cord segments and connected to an electrical stimulation unit (both Medtronic). At least one month after implantation, we developed a cardiovascular optimized stimulation paradigm, that excited sympathetic preganglionic neurons but did not elicit skeletal muscle contraction (confirmed with electromyography; Fig A). We measured beat‐by‐beat blood pressure (photoplethysmography), cardiac function (echocardiography), and cerebral blood flow regulation (transcranial Doppler), in the supine position and in response to sit‐up, as well as cognitive function (Stroop test) with and without (in randomized order) cardiovascular optimized stimulation. Statistics on only one to three individuals is not typically recommended and was not performed.RESULTSTargeted cardiovascular electrical stimulation resulted in: [1] abrogated orthostatic hypotension (–39mmHg and severe presyncope vs. −8mmHg and absence of symptoms; Fig A,B); [2] maintained stroke volume (−32ml vs. −8ml; Fig 1E) and cerebral blood flow (−25 cm/s vs. −6cm/s; Fig B) during sit‐up; and [3] restored neurovascular coupling Fig C (+0% vs. 18%); and Stroop performance (P3–P2 time: 42s vs. 21s). Increased low‐frequency power of systolic blood pressure oscillations suggest supraspinal medullary sympathetic control of blood pressure is restored Fig D.CONCLUSIONSNeuroprosthetic modulation of spinal cord circuitry caudal to injury can restore normal autonomic control, which challenges our dogmatic understanding of the inherent functionality of the autonomic pathways in the spinal cord after injury. This data may represent the dawn of a new age for neuroprosthetic management of autonomic and cardiovascular heath.Support or Funding InformationCraig Neilsen Foundation, Rick Hansen Institute, Helmsley Foundation Research Trust.

Heart rate and blood pressure control in obesity - how to detect early dysregulation?

Obesity is accompanied by many severe complications including various cardiovascular disorders. An impairment of cardiovascular control by autonomic nervous system could be one of the possible links between obesity and cardiovascular complications development. The aim of this study was to compare spontaneous heart rate and systolic blood pressure oscillations reflecting cardiovascular autonomic control of young obese subjects with normal control subjects by linear and nonlinear methods and to find sensitive markers of early autonomic dysregulation. Continuous recordings of beat-to-beat systolic blood pressure and RR intervals from ECG were obtained from 40 obese subjects (25 female, age 14·2 [13·1-16·1] (median [interquartile range]) years) and gender and age matched non-obese control subjects. In addition to linear measures (time and frequency domain), we performed recurrence quantification analysis (RQA) and multiscale entropy analysis for both signals. While no significant differences in heart rate and systolic blood pressure dynamics were detected by linear measures and MSE, analysis of recurrence plots from RR intervals time series showed significant differences - indices trapping time and maximal length of vertical from RQA were significantly higher in obese compared to control group. We conclude that heart rate and blood pressure control by autonomic nervous system in young obese subjects is relatively well preserved. However, novel RQA-related measures are able to detect early subtle abnormalities in cardiac autonomic control in obese subjects indicating decreased signal complexity.

Impact and management of physiological calibration in spectral analysis of blood pressure variability.

Physiological calibration (Physiocal) improves the quality of continuous blood pressure (BP) signal from finger. However, the effects of Physiocal on spectral characteristics of systolic BP (SBP) variability are not well-known. We tested the hypothesis that the use of Physiocal may alter the results on SBP variability when compared with BP recording without Physiocal. Continuous BP was recorded simultaneously from fingers of both arms during 10-min standing by two Nexfin devices, one with (ON) and the other without (OFF) Physiocal (n = 19). Missing SBP values in ON signal were linearly interpolated over Physiocal sequences (ONinter). The OFF signal was analyzed without any corrections (OFFreference) and after linear interpolation of corresponding sequences when Physiocal appeared in the ON signal (OFFinter). Mean low frequency power of SBP oscillations (LFSBP, 0.04–0.15 Hz) did not differ between the OFFreference, OFFinter, and ONinter. However, LFSBP deviated more from OFFreference when analyzed from ONinter compared with the analysis from OFFinter [median (interquartile range): 14.7 (4.6–38.6) vs. 0.9 (0.5–1.8) %, p < 0.05]. In conclusion, the use of Physiocal had a significant effect on the spectral SBP variability that overwhelms the impact of linear interpolation of short data sequences. Therefore, caution is needed when comparing SBP variability between BP datasets acquired with and without Physiocal.

Oscillatory behavior of ventricular action potential duration in heart failure patients at respiratory rate and low frequency.

Oscillations of arterial pressure occur spontaneously at a frequency of approximately 0.1 Hz coupled with synchronous oscillations of sympathetic nerve activity (“Mayer waves”). This study investigated the extent to which corresponding oscillations may occur in ventricular action potential duration (APD). Fourteen ambulatory (outpatient) heart failure patients with biventricular pacing devices were studied while seated upright watching movie clips to maintain arousal. Activation recovery intervals (ARI) as a measure of ventricular APD were obtained from unipolar electrograms recorded from the LV epicardial pacing lead during steady state RV pacing from the device. Arterial blood pressure was measured non-invasively (Finapress) and respiration monitored. Oscillations were quantified using time frequency and coherence analysis. Oscillatory behavior of ARI at the respiratory frequency was observed in all subjects. The magnitude of the ARI variation ranged from 2.2 to 6.9 ms (mean 5.0 ms). Coherence analysis showed a correlation with respiratory oscillation for an average of 43% of the recording time at a significance level of p < 0.05. Oscillations in systolic blood pressure in the Mayer wave frequency range were observed in all subjects for whom blood pressure was recorded (n = 13). ARI oscillation in the Mayer wave frequency range was observed in 6/13 subjects (46%) over a range of 2.9 to 9.2 ms. Coherence with Mayer waves at the p < 0.05 significance level was present for an average of 29% of the recording time. In ambulatory patients with heart failure during enhanced mental arousal, left ventricular epicardial APD (ARI) oscillated at the respiratory frequency (approximately 0.25 Hz). In 6 patients (46%) APD oscillated at the slower Mayer wave frequency (approximately 0.1 Hz). These findings may be important in understanding sympathetic activity-related arrhythmogenesis.

High-Pass Filter Characteristics of the Baroreflex – A Comparison of Frequency Domain and Pharmacological Methods

Pharmacological methods to assess baroreflex sensitivity evoke supra-physiological blood pressure changes whereas computational methods use spontaneous fluctuations of blood pressure. The relationships among the different baroreflex assessment methods are still not fully understood. Although strong advocates for each technique exist, the differences between these methods need further clarification. Understanding the differences between pharmacological and spontaneous baroreflex methods could provide important insight into the baroreflex physiology. We compared the modified Oxford baroreflex gain and the transfer function modulus between spontaneous RR interval and blood pressure fluctuations in 18 healthy subjects (age: 39±10 yrs., BMI: 26±4.9). The transfer function was calculated over the low-frequency range of the RR interval and systolic blood pressure oscillations during random-frequency paced breathing. The average modified Oxford baroreflex gain was lower than the average transfer function modulus (15.7±9.2 ms/mmHg vs. 19.4±10.5 ms/mmHg, P<0.05). The difference between the two baroreflex measures within the individual subjects comprised a systematic difference (relative mean difference: 20.7%) and a random variance (typical error: 3.9 ms/mmHg). The transfer function modulus gradually increased with the frequency within the low-frequency range (LF), on average from 10.4±7.3 ms/mmHg to 21.2±9.8 ms/mmHg across subjects. Narrowing the zone of interest within the LF band produced a decrease in both the systematic difference (relative mean difference: 0.5%) and the random variance (typical error: 2.1 ms/mmHg) between the modified Oxford gain and the transfer function modulus. Our data suggest that the frequency dependent increase in low-frequency transfer function modulus between RR interval and blood pressure fluctuations contributes to both the systematic difference (bias) and the random variance (error) between the pharmacological and transfer function baroreflex measures. This finding suggests that both methodological and physiological factors underlie the observed disagreement between the pharmacological and the transfer function method. Thus both baroreflex measures contribute complementary information and can be considered valid methods for baroreflex sensitivity assessment.

Low-frequency oscillations in R–R interval and blood pressure across the continuum of cardiovascular risk

The purpose of this study was to assess the power and the frequency of low-frequency (LF; 0.04–< 0.15 Hz) oscillations in systolic blood pressure (SBP) and R–R interval (RRi) across the continuum of risk of cardiovascular disease, including age. A potential confound in such determinations is low spontaneous breathing frequency in some individuals. We measured beat-to-beat SBP, RRi and respiration in healthy YOUNG (33 ± 3 years) and OLDER subjects (62 ± 5 years) and older patients with hypertension (HT, 61 ± 5 years), coronary artery disease without (CAD, 62 ± 5 years) and with type 2 diabetes (CAD + DM, 62 ± 4 years, n = 28 for all groups) during spontaneous breathing at supine rest. Power (Power LF) and median frequency (Med LF) of LF oscillations were calculated by power spectral analysis after removing respiratory effects by least-mean-square adaptive filtering. OLDER had higher Power LF-SBP (5.5 ± 3.0 vs. 3.4 ± 2.5 mmHg 2, p = 0.002) and lower Power LF-RRi than YOUNG (339 ± 460 vs. 575 ± 422 ms 2, p = 0.001) whereas neither variable differed between OLDER and patient groups. Med LF-SBP (0.072 ± 0.009 vs. 0.080 ± 0.011 Hz, p = 0.005) and Med LF-RRi (0.072 ± 0.010 vs. 0.079 ± 0.013 Hz, p = 0.027) were lower in OLDER compared with YOUNG. Compared with OLDER, Med LF-RRi was lower in CAD (0.065 ± 0.006 Hz, p = 0.015) and CAD + DM (0.066 ± 0.008 Hz, p = 0.012); whereas CAD + DM had also lower Med LF-SBP (0.065 ± 0.006 Hz, p = 0.012). No differences were observed between OLDER and HT and between CAD and CAD + DM in these variables. We concluded that age is major determinant of the power of LF oscillations in SBP and RRi at rest, whereas the median frequency of these oscillations is altered also by coronary artery disease.

Longitudinal assessment of the effects of oestrogen on blood pressure and cardiovascular autonomic activity in female rats

1. Published data concerning the effects of ovarian hormones on haemodynamic variability are contradictory. For the first time, the present study used radiotelemetric haemodynamic monitoring to investigate the long-term effects of chronic oestrogen depletion and repletion on cardiovascular autonomic control and arterial baroreflex sensitivity (BRS) in female rats. 2. Blood pressure (BP), heart rate (HR) and +dP/dt(max) of arterial pressure (an estimate of myocardial contractility) were monitored in sham-operated (SO), ovariectomized (OVX) and oestrogen-replaced OVX rats (OVXE2) for 16 weeks. Cardiovascular autonomic control and baroreflexes were assessed by frequency domain analysis of interbeat intervals (IBI) and systolic BP (SBP). 3. Compared with SO rats, OVX rats exhibited no changes in BP, short-lived decreases in HR and sustained reductions in +dP/dt(max) of arterial pressure. The high- (HF; 0.75-3 Hz) and low-frequency (LF; 0.25-0.75 Hz) components of spectral power of IBI were significantly decreased and increased, respectively, by ovariectomy. An increase in the IBI(LF/HF) ratio in OVX rats suggests a shift in the cardiac sympathovagal balance towards sympathetic dominance. Index alpha, the spectral index of spontaneous BRS, was reduced by OVX. 4. Oestrogen replacement caused significant reductions in BP and HR and reversed OVX-induced changes in +dP/dt(max) of arterial pressure and cardiac autonomic activity. The LF oscillations of SBP were reduced in OVXE2 rats, suggesting a reduction in vascular sympathetic tone by oestrogen. 5. These findings highlight the importance of long-term oestrogen therapy in rectifying the detrimental effects of depletion of ovarian hormones on the cardiovascular system and baroreflex.

Effects of aging, hypertension, and diabetes on low‐frequency arterial pressure oscillations

Low‐frequency (LF, 0.04‐0.15 Hz) oscillations of arterial pressure are associated to sympathetic activity. We measured beat‐to‐beat systolic blood pressure (SBP) and respiration for YOUNG (n=39, 34±3 yrs) and OLD (n=40, 64±6 yrs) healthy subjects and patients with hypertension (HT, n=38, 60±7 yrs), coronary artery disease (CAD, n=16, 61±4 yrs) and diabetes (CAD+DM, n=29, 60±6 yrs) at supine rest. Spectral power (LFSBPpower) and center frequency (LFSBPf) of SBP oscillations within LF band were calculated. Adaptive filtering was applied to reduce the effects of slow breaths on SBP oscillations at LF. Significant group‐effects were found in LFSBPpower (YOUNG: 4.0±2.5, OLD 6.1±3.4, HT: 5.2±3.3, CAD: 4.2±2.6 and CAD+DM: 4.1±3.0 mmHg2, p=0.014) and LFSBPf (YOUNG: 0.073±0.015, OLD: 0.064±0.011, HT: 0.068±0.011, CAD: 0.054±0.007 and CAD+DM: 0.056±0.010 Hz, p&lt;0.001). OLD had higher LFSBPpower (p=0.003) and lower LFSBPf (p=0.008) than YOUNG. LFSBPpower and LFSBPf did not differ between OLD and HT, whereas CAD had lower LFSBPf (p&lt;0.001) and tended to have lower LFSBPpower (p=0.050) than OLD. No differences were found in LFSBPpower and LFSBPf between CAD and CAD+DM. We concluded that LF arterial pressure oscillations at resting condition are affected by age and cardiac disease but appear to be unaffected by diabetes in cardiac patients or by hypertension. Supported by Academy of Finland, TEKES Finland and CIHR.

Longitudinal Assessment Of The Modulatory Effect Of Estrogen On Blood Pressure And Cardiac Autonomic Activity In Female Rats

Reported findings on the effect of ovarian hormones on hemodynamic variability are contradictory. In this study we employed radiotelemetric hemodynamic monitoring to investigate the long‐term effect of estrogen depletion and repletion on cardiac autonomic control and baroreflex sensitivity (BRS). Blood pressure (BP), heart rate (HR), and +dP/dtmax (index of myocardial contractility) were monitored in sham‐operated (SO), ovariectomized (OVX), and estrogen‐treated OVX (OVXE2) rats for 16 weeks. Cardiovascular autonomic control was assessed by frequency analysis of interbeat intervals (IBI) and systolic BP (SBP). Compared with SO, OVX rats exhibited sustained reductions in dP/dtmax despite similar BP and HR. High‐frequency (HF, 0.75‐3 Hz), but not low‐frequency (LF, 0.25‐0.75 Hz), bands of IBI were reduced in OVX rats, suggesting attenuated cardiac vagal activity. OVX increased IBILF/HF ratio, indicating increased sympathetic dominance. Indexα, spectral index of BRS, was reduced in OVX rats. E2 replacement decreased BP and HR and reversed the effects of OVX on dP/dtmax and cardiac autonomic activity. LF oscillations of SBP were reduced in OVXE2 rats, highlighting a reduction in vascular sympathetic tone.Conclusionslong‐term estrogen therapy rectifies the detrimental cardiovascular and baroreflex influences caused by depletion of ovarian hormones.Supported by Grant R01 AA014441 from NIAAA.

Effects of rhythmical muscle tension at 0.1 Hz on cardiovascular resonance and the baroreflex

This paper reports analysis of data from a previous study examining cardiovascular effects of rhythmical skeletal muscle tension (RSMT) at 0.1 Hz. Our analysis examined whether 0.1 Hz RSMT stimulates resonance properties of the cardiovascular system provided by baroreflex (BR) activity. Thirty-seven study participants tensed their large skeletal muscles, with and without crossing their legs, for 3-min periods at a rate of six tension/relaxation cycles/min. Tensing periods were preceded and followed by 3-min rest periods. RSMT elicited high-amplitude 0.1 Hz oscillations in the cardiovascular system. We found increases in spectral power of ECG R–R interbeat interval (RRI), systolic blood pressure (SBP) and pulse transit time (PTT) at this frequency. The increases in SBP and PTT oscillations were greater than those in RRI. Only in SBP and PTT did total variability (standard deviation) increase. The phase angle between RRI and SBP oscillations was ∼45°. Although alpha low-frequency baroreflex gain was attenuated by RSMT, it was not significantly changed at 0.1 Hz, consistent with BR-induced resonance effects. Our results are consistent with previous observations that 0.1 Hz RSMT is effective in treating vasovagal reactions and indicate that the pathway is through resonance characteristics of the BR system. Implications for resonance applications for resonance in the sympathetically mediated vascular tone baroreflex closed loop are discussed.

Periodic squat‐stand: A new approach for assessment of cardiac baroreflex function in humans

A new approach for assessment of baroreflex function in humanss was developed in this study. Arterial pressure and R‐R interval were recorded in 10 healthy young (30 ± 5 yrs) and 8 elderly subjects (66 ± 6 yrs). Periodic squat‐stand maneuvers were performed at the frequencies of 0.05 and 0.1Hz respectively to produce large oscillations in arterial pressure to stimulate the baroreflex. Transfer function between changes in arterial pressure and R‐R interval was estimated to assess the cardiac baroreflex sensitivity (gain) and the temporal relations (phase) between these variables. During squat‐stand maneuvers, spectral power of oscillations in systolic blood pressure at the frequency of 0.05 Hz was 374 ± 191 mmHg2 in young and 561± 321 mmHg2 in the elderly, and at the 0.1Hz was 253 ± 119 mmHg2 in young and 203 ± 87 mmHg2 in the elderly. In response to these changes in arterial pressure, large oscillations in R‐R interval also were created at the frequencies of 0.05 and 0.1Hz respectively. When compared with the young, transfer function gain was reduced, while the phase became more negative in the elderly. In conclusion, periodic squat‐stand maneuvers produced large and coherent oscillations in arterial pressure and R‐R interval. Transfer function analysis between these variables provides a new and widely available method for assessment of dynamic baroreflex function in humans. Application of this method showed that not only was cardiac baroreflex sensitivity was reduced, but also the heart rate response to changes in arterial pressure was delayed in the elderly.

The Effects on Cardiovascular Autonomic Control of Repetitive Arousal from Sleep

To quantitatively assess autonomic cardiovascular control in normal young adults following exposure to repetitive acoustically-induced arousals from sleep. Respiration, R-R interval (RRI) and noninvasive measurements of continuous arterial blood pressure were monitored in subjects during the transition from relaxed wakefulness to stable Stage 2 sleep. These measurements were made under undisturbed conditions or conditions in which transient arousals were induced repetitively by acoustic stimulation. A mathematical model was used to partition the fluctuations in RRI into a component ("RSA") correlated with respiration and a component ("A representing baroreflex control of heart rate. The magnitudes and forms of each component before and after exposure to repetitive arousals were compared Sleep disorders laboratory in a university setting. Ten healthy young adults (5 male, 5 female) with an average age of 20.4 +/- 2.0 y and mean body-mass index of 23.8 +/- 2.9 kg/m2. Each subject participated in multiple sleep studies consisting of 4 conditions with 2 nights in each condition. The first condition consisted of undisturbed sleep (control), while in the other 3 conditions, the subjects were aroused from sleep by repetitive auditory stimuli applied continuously over a duration of 50 minutes, with periodicities of 30 seconds, 1 minute, and 2 minutes of sleep. Exposure to repetitive arousal (RA) did not alter mean heart rate or blood pressure. However, ABR and RSA gains estimated using the model, increased from the onset of Stage 1 sleep to the start of stable Stage 2 sleep under the control condition, but remained unchanged in all RA conditions. There were also significant increases in low-frequency oscillations of systolic blood pressure in the RA conditions versus no change in the control condition. Exposure to RA over durations approximating an hour produces cumulative effects on autonomic control that are subtle and can only be detected when advanced signal processing methods are employed. More specifically, the increases in ABR and RSA gains that accompany increasing sleep depth in normal sleep are prevented from occurring.

A simplified two-component model of blood pressure fluctuation

We propose a simple moving-average (MA) model that uses the low-frequency (LF) component of the peroneal muscle sympathetic nerve spike rate (LF(spike rate)) and the high-frequency (HF) component of respiration (HF(Resp)) to describe the LF neurovascular fluctuations and the HF mechanical oscillations in systolic blood pressure (SBP), respectively. This method was validated by data from eight healthy subjects (23-47 yr old, 6 male, 2 female) during a graded tilt (15 degrees increments every 5 min to a 60 degrees angle). The LF component of SBP (LF(SBP)) had a strong baroreflex-mediated feedback correlation with LF(spike rate) (r = -0.69 +/- 0.05) and also a strong feedforward relation to LF(spike rate) [r = 0.58 +/- 0.03 with LF(SBP) delay (tau) = 5.625 +/- 0.15 s]. The HF components of spike rate (HF(spike rate)) and SBP (HF(SBP)) were not significantly correlated. Conversely, HF(Resp) and HF(SBP) were highly correlated (r = -0.79 +/- 0.04), whereas LF(Resp) and LF(SBP) were significantly less correlated (r = 0.45 +/- 0.08). The mean correlation coefficients between the measured and model-predicted LF(SBP) (r = 0.74 +/- 0.03) in the supine position did not change significantly during tilt. The mean correlation between the measured and model-predicted HF(SBP) was 0.89 +/- 0.02 in the supine position. R(2) values for the regression analysis of the model-predicted and measured LF and HF powers indicate that 78 and 91% of the variability in power can be explained by the linear relation of LF(spike rate) to LF(SBP) and HF(Resp) to HF(SBP). We report a simple two-component model using neural sympathetic and mechanical respiratory inputs that can explain the majority of blood pressure fluctuation at rest and during orthostatic stress in healthy subjects.

Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients

Sibutramine, a serotonin and norepinephrine transporter blocker, is a common adjunctive obesity treatment. Acute studies in healthy subjects suggested that an inhibitory central nervous mechanism might attenuate the peripheral stimulatory effect on the sympathetic nervous system. This notion has not been tested in overweight and obese patients. We conducted a randomized, controlled clinical study in hypertensive patients with BMI > or = 27 to < 40 kg/m(2). After 4 week placebo run-in period patients were randomized to four different antihypertensive treatments or placebo. After 4 weeks of antihypertensive therapy, patients were additionally treated with sibutramine 15 mg o. d. for 3 months. Patients underwent cardiovascular autonomic reflex testing and a graded head-up tilt test at the end of each phase. Mean body weight decreased from 98.5+/-4 to 94.7+/-4 kg (p<0.05) between end of placebo run-in and end of sibutramine treatment. Supine blood pressure was 154+/-3/80+/-2, 145+/-3/76+/-2 and 150+/-3/79+/-2mmHg at the end of placebo run-in, after antihypertensive titration (ns) and end of sibutramine treatment (ns), respectively. Blood pressure was affected similarly during head up tilt testing. The systolic blood pressure response to cold pressor testing was diminished with sibutramine (p<0.01). Sibutramine decreased low frequency systolic blood pressure oscillations in the supine position (p<0.01). Resting blood pressure tends to increase with sibutramine, whereas blood pressure during sympathetic stimulation and low frequency blood pressure oscillations are decreased. These paradoxical changes are consistent with previous studies in healthy subjects and suggest a combination of peripheral and central nervous system mechanisms.