Baroreflex Sensitivity Index Research Articles

TRANSFER ENTROPY ESTIMATION SUPPLEMENTS TIME-DOMAIN BEAT-TO-BEAT BAROREFLEX SENSITIVITY INDEX UNDER POSTURAL STRESS

Baroreflex mechanism plays a vital role in cardiovascular regulation by contributing in sympathetic-vagal imbalance triggered by baroreceptor reflex. This study estimates BRS (Baroreflex Sensitivity) index from beat-to-beat systolic blood pressure (SBP) and RR interval (RRi) series using time-domain windowed cross-correlation method. This index is supplemented by an information domain technique called Transfer Entropy (TE) is applied to decipher the directional coupling between SBP and RRi series. The study is performed on EUROBAVAR data. The results show that BRS index calculated is large (1.157±0.533) in supine position which supplemented by TE (SBP-RR) of (0.129±0.09) as compared to standing position for which BRS index is (0.866±0.472) and a TE (SBP-RR) of (0.04±0.03) for EUROBAVAR data with a p-value<0.05. Also, it is found that both the TE indices i.e. from SBP to RR and from RR to SBP show correlated results with the time domain BRS index in both supine and standing positions. Further, the cases with possible BRS failure are having very small values of BRS index, which are not assigned any value by prevalent methods. This shift is absent in BRS failure patients which is supplanted by TE (RR-SBP) sharing more information bits than TE (SBP-RR). Further, it is observed that patients having baroreflex impairment show reversal of information flow which is indicated by a larger TE (RRSBP) index as compare to TE (SBP-RR) index. Time domain BRS index lacks directional information which is provided by TE and hence this supplemental information gives better interpretation of BRS index especially in patients having suppressed baroreflex. Index Terms: Baroreflex sensitivity, Directional coupling, Cross-correlation, and Transfer entropy

The Estrogen‐Mediated Control Of Blood Pressure And Cardiovascular Autonomic Control Are Differentially Modulated By Endothelial And Neuronal Nitric Oxide Synthases

Estrogen (E2) replacement lowers blood pressure (BP) and improves the cardiovascular autonomic control in ovariectomized (OVX) rats. We investigated whether constitutive and/or inducible nitric oxide synthase (NOS) modulate these E2 effects. We evaluated changes in BP, myocardial contractility (dP/dtmax), and power spectral indices of hemodynamic variability following inhibition of eNOS (L‐NIO), nNOS (NPLA), or iNOS (1400W) in telemetered OVX rats treated for 16 weeks with (OVXE2) or without (control, OVXC) E2. OVXE2 rats exhibited (i) reduced BP, and increased dP/dtmax, (ii) enhanced cardiac parasympathetic influence as reflected by decreases in low‐frequency/high‐frequency ratio of interbeat intervals (IBILF/HF), and (iii) reduced LF oscillations of systolic BP, suggesting a reduced vasomotor sympathetic tone. L‐NIO elicited a shorter‐lived pressor response in OVXE2, than in OVXC, rats along with reductions in dP/dtmax and increases in the spectral index of spontaneous baroreflex sensitivity (index α). NPLA reduced BP and increased IBILF/HF ratio in OVXE2 but not in OVXC rats. No hemodynamic changes were caused by 1400W. Overall, eNOS and nNOS exert contrasting tonic modulatory BP effects, which comprise induction of hypotension and hypertension, respectively, in OVXE2 rats. Baroreflex facilitation and dP/dtmax reductions might explain the shorter pressor action of L‐NIO in OVXE2 rats.

Individual Differences in Cardiac and Vascular Components of the Pressor Responses to Isometric Handgrip Exercise in Humans

The aim of this study was to test the hypotheses that, in humans, cardiac output (CO) and total peripheral vascular resistance (TPR) responses to isometric exercise vary among individuals, and that the individual differences are related to the muscle metaboreflex and the arterial baroreflex functions. Healthy subjects (n = 32) performed 1‐min isometric handgrip exercise (HG) at 50% of maximal voluntary contraction, followed by a 4‐min period of post‐exercise muscle ischemia (PEMI) to selectively maintain activation of the muscle metaboreflex. In 11 subjects the pressor response to HG occurred solely by the increase in CO, but in 18 subjects it occurred due to both the increases in CO and TPR, and further it occurred solely via the increase in TPR in 3 subjects. Thus the pressor components varied widely among subjects. The CO and TPR responses during HG were positively correlated with those responses during PEMI, respectively. In addition, the CO response to PEMI was negatively correlated with the PEMI‐induced changes in an index of cardiac vagal tone and cardiac baroreflex sensitivity. We conclude that CO and TPR responses to HG vary among individuals, and that the individual differences in components of the pressor response could be attributed in part to the variations in the muscle metaboreflex and the arterial baroreflex functions. This study was supported by the grants from Japan Society for the Promotion of Science.

Influence of acute sleep deprivation on cardiovascular parameters in female zucker obese and lean rats

There is a reciprocal relationship between sleep duration and weight gain. However, the consequences of this relationship on the cardiovascular system over an entire life span are still not fully elucidated. We examined the effect of acute sleep deprivation (SD) on baroreflex sensitivity and blood pressure in Zucker rats of different ages. Female lean and obese Zucker rats at 3, 6 and 15 months of age were assigned to SD or control (CTRL) groups. After a 6 h period of the SD procedure (6 h of gentle handling) or CTRL procedure (an equivalent period without handling), the animals were anesthetized for surgical catheterization of the femoral artery and vein. To evaluate the baroreflex sensitivity index, bolus infusions of phenylephrine (bradycardia response) and sodium nitroprusside (tachycardia response) were administered. Obesity resulted in dysfunctional tachycardia responses at 3 months of age. At 6 and 15 months of age, both bradycardia and tachycardia responses were significantly lower in obese animals than those in lean animals. At 15 months of age, interactions among obesity, SD and aging produced the most marked effects on the cardiovascular system (increased mean arterial pressure and heart rate and decreased baroreflex sensitivity). Therefore, these results suggest that there is no direct relationship between baroreflex imbalance and an increase in arterial pressure.

A randomized controlled trial of exercise training on cardiovascular and autonomic function among renal transplant recipients

There are conflicting data regarding the effects of renal transplantation (RT) on uraemic autonomic dysfunction. Moreover, no study has examined the impact of physical training on the cardiac autonomic function in RT patients. Thus, we studied the effects of exercise training on heart rate variability (HRV) and arterial baroreflex sensitivity (BRS), which are sensitive markers of cardiac autonomic outflow, in RT recipients. Eleven patients (Exercise group-aged 52.1 ± 5.6 years) were studied before and after 6 months of exercise training. Twelve age- and sex- matched RT patients (Sedentary) and 12 healthy sedentary individuals (Healthy), who remained untrained, served as controls. At baseline and follow-up, all the subjects underwent cardiopulmonary exercise testing for the evaluation of peak oxygen consumption (VO2peak), a tilt test for the evaluation of BRS and baroreflex effectiveness index (BEI) and an ambulatory 24-h Holter monitoring for time- and frequency-domain measures of HRV. In the exercise group, VO2peak increased by 15.8% (P < 0.05) and all depressed HRV and BRS indices were significantly improved after training. Specifically, the standard deviation of all normal-to-normal (NN) intervals (SDNN) significantly increased by 92.5%, the root-mean-square of the differences between consecutive NN intervals by 45.4%, the percentage value of NN50 count by 58.2%, the high-frequency by 74.8% and low-frequency spectral power by 41.6%, BRS by 43.7% and BEI by 57.3%. None of the variables studied was altered over time in either control group. The increased cardiorespiratory fitness by exercise training was associated with an improved BRS function and a modification of the sympathovagal control of HRV towards a persistent increase in parasympathetic tone. These alterations may lead to a better cardiovascular prognosis in RT recipients.

Abstract 413: Electroacupuncture Improves Arterial Baroreflex and Chemoreflex Sensitivity in Angiotensin II-induced Hypertension in Rats

Despite the use of electroacupuncture (EA) to treat a number of cardiovascular diseases, little is known about the mechanisms that underlie its actions. It is well known that renin-angiotensin system plays a major role in pathogenesis of hypertension. The purpose of this study was to examine the influence of EA stimulation of ST 36 on arterial baro- and chemoreflex sensitivity in angiotensin (Ang) II-induced hypertension in rats. Four groups of SD rats (n=8/group) were implanted with subcutaneous osmotic minipumps for infusion of Ang II (300 ng/kg/min) or saline control, with or without EA stimulation. EA groups underwent a 2 Hz EA treatment at the acupoints ST36 or a non-acupoint with the intensity increasing stepwise from 0.5-1-1.5 mA once a day for 30 min. Baroreflex sensitivity index was calculated on the basis of reflex changes in heart rate (HR) related to the arterial pressure (AP) changes induced by phenylephrine or sodium nitroprusside injection, and chemoreflex sensitivity was evaluated by intravenous injections of increasing doses of potassium cyanide (KCN). After 4 weeks of treatment, Ang II significantly increased mean arterial pressure (107±2 and 139±2 mmHg in control vs. Ang II group). Baroreflex sensitivity to AP rises and falls were also impaired in Ang II infusion group (1.3±0.08 and 2.1 ±0.18 bpm/mmHg) compared with those in control group (1.7±0.08 and 2.7±0.06 bpm/mmHg). EA stimulation of ST 36 on Ang II infusion rats significantly improved the impaired baroreflex sensitivity (1.7±0.06 and 2.6±0.1 bpm/mmHg, P &lt; 0.05). In addition, the bradycardic and pressor responses evoked by KCN injections were attenuated in Ang II infusion rats (23±9 bpm and 7±1 mmHg in Ang II group vs. 78±7 bpm and 22±3mmHg in control group, P &lt; 0.05), while EA stimulation improved both chemoreflex responses in AngII rats (84±15 bpm and 32±5 mmHg, P&lt;0.05). In contrast, EA stimulation had no significant effect on control group. These results indicate that EA stimulation improves arterial baroreflex function and chemoreflex sensitivity in conditions of high Ang II.

Relationship between carotid artery mechanics and the spontaneous baroreflex

This study addressed the relationship between spontaneous baroreflex sensitivity and carotid mechanical properties in a clinical setting. In 191 normal volunteers (age range 20-60 years, mean 44 ± 13), spontaneous indices of baroreflex regulation were obtained noninvasively in the time (baroreflex slope, BRS) and frequency domains (α index and systolic arterial pressure-RR interval transfer gain) as well as using an exogenous autoregressive causal model (A.XAR); carotid mechanical properties were estimated by ultrasound. The link between mechanical measures and spontaneous baroreflex indices was explored by multivariate analysis and linear modeling. Participants were divided into five groups according to age decades. With advancing age we observed a decrease in spontaneous baroreflex indices (BRS from 31.2 to 16.3; α index from 27.4 to 13.6; RR-SAP gain at high frequency from 31 ± 3.0 to 14 ± 3.0 ms/mmHg all P < 0.001) and increase in carotid intima-media thickness (IMT: from 0.53 to 0.69 mm; P < 0.001) and stiffness (local wave speed: from 4.0 to 6.9 m/s; both P < 0.001). A significant correlation was found between spontaneous indices of baroreflex sensitivity and carotid mechanical properties, particularly wave speed (r = -0.328, P < 0.001). After adjusting for age and sex, a significant correlation remained between RR-SAP gain and wave speed and between A.XAR and IMT. Factor analysis and automatic linear modeling confirmed the observation that mechanical carotid properties are strong predictors of the age-related reduction of spontaneous baroreflex. A significant correlation between spontaneous baroreflex indices and local carotid mechanical properties supports the idea that they should be considered in the physiology of baroreflex regulation.

Improvement in Cardiovascular Indices After Roux-en-Y Gastric Bypass or Sleeve Gastrectomy for Morbid Obesity

Morbidly obese patients display cardiac abnormalities which are partially reversed after weight loss. The aim of the present study was to assess the potential difference in cardiovascular disease indices between patients who underwent either gastric bypass surgery or sleeve gastrectomy. Thirty-seven morbidly obese patients who underwent either Roux-en-Y gastric bypass (RYGB) (n = 14) or SG (n = 23) were examined before, 3 and 6 months after surgery. Indices of cardiac autonomic nervous system activity were evaluated, namely baroreflex sensitivity (BRS) and heart rate variability (HRV). A complete echocardiographic study was performed in a subgroup of 17 patients (RYGB 8, SG 9) preoperatively and 6 months after surgery, evaluating epicardial fat thickness, aortic distensibility, left ventricular (LV) Tei index, left atrium diameter, ejection fraction, and LV mass. All subjects experienced significant (p < 0.001) and similar weight loss independently of the type of operation. BRS and HRV indices improved significantly and to the same degree after surgery in both groups. In the echocardiographic study, all parameters improved significantly at 6 months in comparison with the baseline values. In addition, the RYGB group displayed significantly greater reduction in epicardial fat thickness (p = 0.007) and also tended to have a better LV performance as expressed by the lower values of the Tei index (p = 0.06) compared to the SG group 6 months after surgery. Both RYGB and SG exert comparable effects on weight loss and improvement of cardiovascular parameters. RYGB displays a more beneficial influence on epicardial fat thickness and left ventricular performance than SG.

Autonomic Dysfunction in Heart Failure and Renal Disease

EDITORIAL article Front. Physiol., 26 June 2012Sec. Integrative Physiology Volume 3 - 2012 | https://doi.org/10.3389/fphys.2012.00219

Comparison of the Diagnostic Accuracy of Non-Invasive Indices of Baroreflex Sensitivity in the Assessment of Diabetic Cardiac Autonomic Neuropathy

Comparison of the Diagnostic Accuracy of Non-Invasive Indices of Baroreflex Sensitivity in the Assessment of Diabetic Cardiac Autonomic Neuropathy

Effects of genetic vs. environmental factors on cardiovascular autonomic function: a twin study

Cardiovascular autonomic function is often assessed in patients with diabetes by measuring heart rate variability and baroreflex sensitivity, the heritability of which is not fully understood. The present study was aimed to determine the effects of genetic and environmental factors on heart rate variability and baroreflex sensitivity in monozygotic and dizygotic adult healthy twin pairs. A total of 101 (63 monozygotic, 38 dizygotic) adult twin pairs (n = 202; mean age 44.3 years) were investigated. Anthropometric variables and serum metabolic markers were measured, while environmental characteristics were evaluated by questionnaires. Linear and spectral indices of heart rate variability and baroreflex sensitivity were determined by non-invasive methods. All measurements were adjusted for age and gender (model 1) and for all significantly relevant covariates (model 2). Heritability A-C-E structural equation models were used for characterizing the proportion of additive genetic, shared and unshared environmental influences. Genetic influence of different cardiovascular autonomic indices was estimated between 10.3 and 39.4%, common environmental influence was found between 0.0 and 33.2%, while unshared environmental influence was observed between 60.6 and 81.4% in model 1 analysis. In multivariable-adjusted heritability estimates (model 2), the magnitude of the genetic effects decreased to 0.0%, common environmental influence was nearly unchanged (values between 4.4 and 14.5%), while unshared environmental influence slightly increased (values between 85.5 and 96.5%). Unshared environmental but not genetic factors have substantial influence on cardiovascular autonomic function, suggesting that appropriate treatment of all modifiable environmental factors is of importance in order to prevent or ameliorate cardiovascular autonomic neuropathy.

Assessment of sympathetic index from the Valsalva maneuver

Blood pressure (BP) decline and recovery during the Valsalva maneuver (VM) are used to evaluate the degree of sympathetic failure (SF) but a reliable sympathetic index (SI) derived from VM is lacking. Patients with mild (n=20), moderate (n=65), and severe (n=60) SF and 23 healthy controls were evaluated using a standardized battery of autonomic tests. SF was defined as mild (associated with reduced sudomotor volumes at distal leg); moderate (associated with a fall in systolic BP ≥10< 30 mm Hg during the tilt test); and severe (associated with a fall in systolic BP ≥30 mm Hg during the tilt test). Six SIs were compared: SI1 (BP fall during phase 2), SI2 (BP recovery during phase 2), SI3 (the difference in BP between baseline and the end of phase 2), SI4 (the magnitude of phase 4), SI5 (BP recovery time), and SI6 (baroreflex sensitivity index). All indexes showed overall significant differences among tested groups (p<0.05). Only SI3 differentiated all subject groups. Compared to other SIs, SI3 correlated the most with orthostatic hypotension (OH; r=0.62, p < 0.05) during the tilt. SI3 is the optimal method for calculation of SI since it 1) easily differentiates between healthy controls and those with SF; 2) correlates with the OH, a proxy for a sympathetic failure; 3) tracks the full spectrum of SF (mild-moderate-severe). SI3 expands the utility of quantitative autonomic testing.

Clinical and haemodynamic correlates of heart rate turbulence as a non-invasive index of baroreflex sensitivity in chronic heart failure

HRT (heart rate turbulence), describing the heart rate changes following a premature ventricular contraction, has been regarded as an indirect index of baroreflex function. However, limited data are available on its relationship with invasive assessment by phenylephrine injection (Phe-slope). In the present study, we therefore compared these methodologies in a series of patients with HF (heart failure) in which both measures together with clinical and haemodynamic data were available. HRT parameters [TO (turbulence onset) and TS (turbulence slope)] were measured from 24-h Holter recordings obtained within 1 week of baroreflex sensitivity assessment and right heart haemodynamic evaluation (Swan-Ganz catheter). HRT was computable in 135 out of 157 (86%) patients who had both a phenylephrine test and haemodynamic evaluation. TO and TS significantly correlated with Phe-slope (r=−0.39, P<0.0001 and r=0.66, P<0.0001 respectively). Age, baseline heart rate, LVEF (left ventricular ejection fraction), PCP (pulmonary capillary pressure), CI (cardiac index) and sodium were significant and independent predictors of Phe-slope, accounting for 51% of its variability. Similarly, age, baseline heart rate and PCP, and NYHA (New York Heart Association) classes III–IV were independent predictors for TS and explained 48% of its variability, whereas only CI and LVEF were found to be significantly related to TO and explained a very limited proportion (20%) of the variability. In conclusion, these results suggest that HRT may be regarded as a surrogate measure of baroreflex sensitivity in clinical and prognostic evaluation in patients with HF.

Frequency Analysis Unveils Cardiac Autonomic Dysfunction after Mild Traumatic Brain Injury

Long-term mortality is increased after mild traumatic brain injury (mTBI). Central cardiovascular-autonomic dysregulation resulting from subtle, trauma-induced brain lesions might contribute to cardiovascular events and fatalities. We investigated whether there is cardiovascular-autonomic dysregulation after mTBI. In 20 mTBI patients (37±13 years, 5-43 months post-injury) and 20 healthy persons (26±9 years), we monitored respiration, RR intervals (RRI), blood pressures (BP), while supine and upon standing. We calculated the root mean square successive RRI differences (RMSSD) reflecting cardiovagal modulation, the ratio of maximal and minimal RRIs around the 30th and 15th RRI upon standing (30:15 ratio) reflecting baroreflex sensitivity (BRS), spectral powers of parasympathetic high-frequency (HF: 0.15-0.5 Hz) RRI oscillations, of mainly sympathetic low-frequency (LF: 0.04-0.15 Hz) RRI oscillations, of sympathetic LF-BP oscillations, RRI-LF/HF-ratios reflecting sympathovagal balance, and the gain between BP and RRI oscillations as additional BRS index (BRS(gain)). We compared supine and standing parameters of patients and controls (repeated measures analysis of variance; significance: p<0.05). While supine, patients had lower RRIs (874.2±157.8 vs. 1024.3±165.4 ms), RMSSDs (30.1±23.6 vs. 56.3±31.4 ms), RRI-HF powers (298.1±309.8 vs. 1507.2±1591.4 ms(2)), and BRS(gain) (8.1±4.4 vs. 12.5±8.1 ms·mmHg(-1)), but higher RRI-LF/HF-ratios (3.0±1.9 vs. 1.2±0.7) than controls. Upon standing, RMSSDs and RRI-HF-powers decreased significantly in controls, but not in patients; patients had lower RRI-30:15-ratios (1.3±0.3 vs. 1.6±0.3) and RRI-LF-powers (2450.0±2110.3 vs. 4805.9±3453.5 ms(2)) than controls. While supine, mTBI patients had reduced cardiovagal modulation and BRS. Upon standing, their BRS was still reduced, and patients did not withdraw parasympathetic or augment sympathetic modulation adequately. Impaired autonomic modulation probably contributes to cardiovascular irregularities post-mTBI.

Time–frequency analysis of the baroreflex control of renal sympathetic nerve activity in the rat

Cross-spectral analysis using the short-time Fourier transform (STFT) allows estimating the transfer function between spontaneous fluctuations of arterial pressure (AP) and renal sympathetic nerve activity (RSNA) at the heart rate (HR) frequency, which provides an index of sympathetic baroreflex sensitivity (sBRS) in rats. The method, however, cannot reliably compute more than one value per min. The goal of the present study was to achieve a better temporal resolution by using advanced methods. The first method is the continuous wavelet transform (CWT) using the Morlet wavelet. The second method is based on the empirical mode decomposition (EMD), a method that decomposes a signal into a sum of oscillating components. Using both methods, the transfer function was estimated over periods of 10 s. The two methods, together with STFT, were applied to AP and RSNA signals that were simultaneously recorded in conscious, freely behaving rats ( n = 10) during 1 h. When considering 1-h mean sBRS values obtained in each rat, both methods showed a strong correlation with STFT ( R = 0.96 and 0.91 for CWT and EMD, respectively, both P < 0.001). In each rat, sBRS values obtained by the CWT and EMD methods were tightly correlated ( R = 0.93 ± 0.01, n = 294 ± 13, P < 0.001). With both methods, high-frequency variations of sBRS (0.0083–0.5 Hz) accounted for about 40% of its overall variability. In urethane-anaesthetized rats ( n = 9), sBRS variability computed by either method was reduced by about two-thirds ( P < 0.001). Improving temporal resolution of sBRS computation reveals that in rats, sBRS exhibits fast, short-lasting fluctuations. These fluctuations largely depend on the state of vigilance.

Attenuation of sympathetic baroreflex sensitivity during the onset of acute mental stress in humans

Mental stress consistently induces a pressor response that is often accompanied by a paradoxical increase of muscle sympathetic nerve activity (MSNA). The purpose of the present study was to evaluate sympathetic baroreflex sensitivity (BRS) by examining the relations between spontaneous fluctuations of diastolic arterial pressure (DAP) and MSNA. We hypothesized that sympathetic BRS would be attenuated during mental stress. DAP and MSNA were recorded during 5 min of supine baseline, 5 min of mental stress, and 5 min of recovery in 32 young healthy adults. Burst incidence and area were determined for each cardiac cycle and placed into 3-mmHg DAP bins; the slopes between DAP and MSNA provided an index of sympathetic BRS. Correlations between DAP and MSNA were strong (> 0.5) during baseline in 31 of 32 subjects, but we evaluated the change in slope only for those subjects maintaining a strong correlation during mental stress (16 subjects). During baseline, the relation between DAP and MSNA was negative when expressed as either burst incidence [slope = -1.95 ± 0.18 bursts·(100 beats)⁻¹)·mmHg⁻¹; r = -0.86 ± 0.03] or total MSNA [slope = -438 ± 91 units·(beat)⁻¹ mmHg⁻¹; r = -0.76 ± 0.06]. During mental stress, the slope between burst incidence and DAP was significantly reduced [slope = -1.14 ± 0.12 bursts·(100 beats)⁻¹·mmHg⁻¹; r = -0.72 ± 0.03; P < 0.01], indicating attenuation of sympathetic BRS. A more detailed analysis revealed an attenuation of sympathetic BRS during the first 2 min of mental stress (P < 0.01) but no change during the final 3 min of mental stress (P = 0.25). The present study demonstrates that acute mental stress attenuates sympathetic BRS, which may partially contribute to sympathoexcitation during the mental stress-pressor response. However, this attenuation appears to be isolated to the onset of mental stress. Moreover, variable MSNA responses to mental stress do not appear to be directly related to sympathetic BRS.

Effects of exercise training on arterial-cardiac baroreflex function in POTS

Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive tachycardia in the upright position. To test the hypothesis that patients with POTS have impaired arterial-cardiac baroreflex function, while exercise training normalizes the baroreflex function in these patients. Seventeen POTS patients aged 27±9 (mean±SD) years underwent an exercise training program for 3months. Arterial-cardiac baroreflex function was assessed by spectral and transfer function analysis of beat-to-beat R-R interval (RRI) and systolic blood pressure (SBP) variability in the supine position and at 60° upright tilt during spontaneous breathing before and after training. Data were compared with 17 healthy sedentary controls. Even though upright heart rate (HR) was greater in patients than controls, indexes of RRI variability did not differ between groups. Transfer function gain (SBP to RRI), used as an index of arterial-cardiac baroreflex sensitivity was similar between patients and controls in both low- (LF, P=0.470) and high-frequency (HF, P=0.663) ranges. Short-term exercise training decreased upright HR and increased RRI variability in POTS patients. LF baroreflex gain increased significantly in the supine position and during upright tilt [analysis of variance (ANOVA), P=0.04 for training], while HF gain increased modestly after training (ANOVA, P=0.105 for training) in these patients; however, the baroreflex gains remained within the normal ranges when compared with healthy controls. These data suggest that patients with POTS have normal arterial-cardiac baroreflex function in both supine and upright postures. Short-term exercise training increases the baroreflex sensitivity in these patients, associated with a decrease in upright heart rate.

213 Mechanism of Cardiovascular Dysfunction in Infants of Active Smokers

Recently we showed that blood pressure and heart rate control is impaired in infants of mothers who smoke. This dysfunction resembles classic orthostatic intolerance and could indicate susceptibility to raised blood pressure later on. We analyzed whether this dysfunction reflects abnormal autonomic neural modulation of the heart, or the vasculature, or both. Methods: Subjects: term-born infants of mothers who smoked during pregnancy (15cigarettes/day; n=15) and infants of non-smokers (n=27). All were examined at least twice between 1 week and 18 months age. Supine blood pressure (BP; Finometer) and heart period (HP) were recorded for 4 min during quiet sleep. We used autoregressive cross-spectral analysis to compare age-related changes in low (LF; 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) power of HP and systolic BP (SBP). The gain of the heart-pressure relationship (α) was estimated by frequency domain analysis. We considered (i) LFHP and LFSAP power as markers of the sympathetic efferent modulation of the heart and blood vessels, respectively, and (ii) α as an index of baroreflex sensitivity. Results: Absolute values of, and variance in HP / BP of infants of smokers and non-smokers were comparable. In tobacco-exposed infants LFSAP (but not LFHP) decreased and α increased with age. Conclusions: Early-life tobacco exposure attenuates sympathetic drive to the blood vessels and augments baroreflex gain but leaves cardiac sympatho-vagal drive unchanged.

利用Volterra-Wiener模型估算壓力反射敏感度－以EUROBAVAR資料庫為例

The short-term control of blood pressure is the arterial baroreflex and the baroreflex sensitivity (BRS) is the indicator that describes such mechanism. The BRS estimation, spontaneous BRS index, is based on beat-to-beat time series analysis of systolic blood pressure and heart rate interval underlying openloop or closed-loop linear model in time or frequency domain. However, the physiological regulatory mechanism of blood pressure is inherently nonlinear and dynamic. It would make a great improvement for accurate assessment of arterial baroreflex by a suitable dynamic nonlinear model. This paper presents a nonlinear Volterra-Wiener model and the Laguerre expansion technique to analyze the changes in systolic arterial blood pressure, as model’s input, and their corresponding changes in heart rate interval, as model ’s output. Compared with the measurements by sequence technique and alpha coefficient technique in EUROBAVAR dataset, we found that the estimates of BRS by the proposed technique were lower either in lying or in standing position and the lying/standing ratio were higher. The proposed technique improves the overestimation of spontaneous BRS index obtained by other approaches such as sequence technique or alpha coefficient technique.

ASSOCIATION OF ARG16GLY POLYMORPHISM OF THE BETA-2 ADRENERGIC RECEPTOR (B2AR) GENE WITH BAROREFLEX SENSITIVITY AND INDICES OF AUTONOMIC CARDIOVASCULAR MODULATION: PP.32.258

Objective: Sympathetic nervous system plays a key role in blood pressure control and functional polymorphisms of the beta-2 adrenergic receptor (B2AR) have been implicated in the pathogenesis of hypertension. In particular, functional polymorphism Arg16Gly (46A–>G rs1042713), has been proved to be of clinical relevance. However, limited information is available on its association with baroreflex sensitivity (BRS) and other parameters of autonomic cardiovascular regulation. Aim of our study was to explore this issue. Methods: In the frame of Medellin's Heart Study, a probabilistic sample of 800 subjects from the general population of Medellin (Colombia) was recruited. Individuals with a diastolic blood pressure (DBP)>70th percentile of distribution curve (DBP>85 mmHg), aged 30-65 years and not receiving antihypertensive therapy, were selected (n = 92). Arg16Gly polymorphism was forward and backward genotyped (accuracy >99%), using automated DNA sequencer 3730XL (ABI-Prism). Cardiovascular autonomic modulation was assessed by computer analysis of 10 min beat-to-beat BP and ECG recordings obtained in supine position (Task Force Monitor). BRS was estimated by sequence method as the slope of spontaneous concomitant increases or decreases in systolic (S)BP and RR interval. Low-frequency (LF) and high-frequency (HF) spectral components of heart rate variability (HRV) were assessed by Fourier analysis and expressed in normalized units (nu). LF/HF ratio was also calculated. Results: Allelic distribution of Arg16Gly polymorphism was in Hardy-Weinberg equilibrium. There was highly significant variation in all parameters between Arg/Arg, Arg/Gly and Gly/Gly genotypes. After adjustment for age, sex, smoking, diabetes, SBP and BMI, subjects with Arg/Arg genotype exhibited significantly lower BRS (p < 0.007), higher HRV sympathetic indices (LF; p < 0.003 and LF/HF; p < 0.002) and lower HRV parasympathetic indices (HF; p < 0.003) than those with Gly/Gly genotype. See table. Conclusions: These results indicate that ADRB2 gene may be involved in the modulation of cardiac baroreflex and HRV in humans. In particular, Arginine homozygous genotype of Arg16Gly polymorphism was associated with a decreased BRS and higher indirect indices of sympathetic activity in subjects with high blood pressure.