Lower Baroreflex Sensitivity Research Articles

Abstract 367: Insulin Resistance is Associated with Increased Sympathetic Activity and Decreased Baroreflex Function in Obese African American Women

Obesity has a greater detrimental impact on the health of African American (AA) women than any other racial or gender group. Nearly 80% of AA women are overweight or obese and have higher incidence of insulin resistance compared to Caucasian women. The sympathetic nervous system (SNS) is increased in obesity and previous studies have reported that it may contribute to insulin resistance. However, most of these studies were performed in Caucasians. Thus, the contribution of the SNS to insulin resistance in African Americans remains unknown.The aim of this study was to determine if sympathetic activity is increased in obese AA women with insulin resistance. A total of 35 obese AA women with metabolic syndrome were studied (age 43±9 years, body mass index 38.7±5.5 Kg/m 2 , percentage body fat 48±4). Insulin sensitivity (SI) was evaluated by frequently sampled intravenous tolerance test and analyzed with Bergman's minimal model (MINMOD). Measurement of sympathetic regulation of vasomotor tone and baroreflex gain were determined with baroreflex-cross spectral analysis. Our results showed that SI was directly associated with baroreflex sensitivity, Figure. Subjects with insulin resistance (SI<3) had lower baroreflex sensitivity compared with those with normal SI (6.2±2.8 vs 10.4±4.5 ms/mm Hg, P=0.009). Subjects with insulin resistance tended to have elevated sympathetic activity as measured by low frequency variability of systolic blood pressure (LF SBP ; 5.9±3.4 vs 3.7±2.0 mm Hg 2 , P=0.057). In conclusion, insulin resistance is associated with decreased baroreflex gain and increased sympathetic activity in obese AA women.

From the First Spectral Analysis of Blood Pressure Variability in the World to the Present Time: Contribution of the Department of Physiology of the Faculty of Medicine, Masaryk University, Brno

The review shows the significance of blood pressure regulation studies conducted during several decades at the Department of Physiology, Faculty of Medicine, Masaryk University, Brno. Continuous non-invasive blood pressure measurement was first introduced and patented here and, with the obtained data, the first spectral analysis of blood pressure was performed. This method was used in many different physiological studies on the relationship of blood pressure regulation to circulatory parameters, breathing, and baroreflex sensitivity. The article deals with studies on risk stratification of sudden cardiac death according to decreased baroreflex sensitivity, 24-hour heart rate variability, the amount of extrasystoles and late potentials. Importance of the new method of determination of one summation risk index is described here. A summary of the new conception of the relationship between low baroreflex sensitivity and hypertension is presented. Here, not only pathological changes of the vessel wall but also increased sympathetic activity and genetic predisposition play a role. Importance of studies conducted in young adults is highlighted, as inherited BRS decrease contributes to earlier blood pressure increase in the young. This research is highly topical, since prevention of hypertension in childhood is possible. Recent studies are dedicated to blood pressure regulation in young diabetics.

Impaired blood pressure control in children with obstructive sleep apnea

Obstructive sleep apnea (OSA) in adults has been associated with hypertension, low baroreflex sensitivity (BRS), a delayed heart rate response to changing blood pressure (heart period delay [HPD]), and increased blood pressure variability (BPV). Poor BRS may contribute to hypertension by impairing the control of blood pressure (BP), with increased BPV and HPD. Although children with OSA have elevated BP, there are scant data on BRS, BPV, or HPD in this group. 105 children ages 7-12 years referred for assessment of OSA and 36 nonsnoring controls were studied. Overnight polysomnography (PSG) was performed with continuous BP monitoring. Subjects were assigned to groups according to their obstructive apnea-hypopnea index (OAHI): primary snoring (PS) (OAHI ≤1event/h), mild OSA (OAHI>1- ≤5events/h) and moderate/severe (MS) OSA (OAHI>5events/h). BRS and HPD were calculated using cross spectral analysis and BPV using power spectral analysis. Subjects with OSA had significantly lower BRS (p<.05 for both) and a longer HPD (PS and MS OSA, p<.01; mild OSA, p<.05) response to spontaneous BP changes compared with controls. In all frequencies of BPV, the MS group had higher power compared with the control and PS groups (low frequency [LF], p<.05; high frequency [HF], p<.001). Our study demonstrates reduced BRS, longer HPD, and increased BPV in subjects with OSA compared to controls. This finding suggests that children with OSA have altered baroreflex function. Longitudinal studies are required to ascertain if this dampening of the normal baroreflex response can be reversed with treatment.

Influence of D,L-Sotalol on Baroreflex Sensitivity Response to Posture Following Coronary Artery Bypass Graft Surgery in Men and Women

Low baroreflex sensitivity (BRS) following coronary artery bypass graft (CABG) surgery increases the risk of sympathetically mediated cardiac arrhythmias. To reduce this risk, D,L-sotalol, a nonselective β-adrenergic receptor antagonist (Class II) and an antiarrhythmic (Class III), is prescribed postoperatively. However, its effect on BRS has not been reported. The purpose of this study was to characterize the influence of D,L-sotalol on BRS measures in supine and standing postures 4 days following CABG surgery. BRS was measured in 27 men and 10 women receiving D,L-sotalol and compared with archival data for 21 men and 10 women obtained prior to the routine administration of D,L-sotalol. In the latter (control) group, 61% had BRS of less than 3 ms/mmHg in the supine posture and 74% in the standing posture compared to 42% with less than 3 ms/mmHg in the supine posture and 65% in the standing posture in the D,L-sotalol group. Men in the D,L-sotalol group showed higher R-R interval and BRS in both supine and standing postures compared with controls. Women in the D,L-sotalol group had higher R-R interval in the supine posture. The higher BRS in men not only reduces the risk of arrhythmias after CABG surgery but may also allow a more rapid circulatory response to the standing posture, thereby decreasing the risk of syncope.

Fetal betamethasone exposure attenuates angiotensin-(1-7)-Mas receptor expression in the dorsal medulla of adult sheep

Glucocorticoids including betamethasone (BM) are routinely administered to women entering into early preterm labor to facilitate fetal lung development and decrease infant mortality; however, fetal steroid exposure may lead to deleterious long term consequences. In a sheep model of fetal programming, BM-exposed (BMX) offspring exhibit elevated mean arterial pressure (MAP) and decreased baroreflex sensitivity (BRS) for control of heart rate by 0.5-years of age associated with changes in the circulating and renal renin-angiotensin systems (RAS). In the brain solitary tract nucleus, angiotensin (Ang) II actions through the AT1 receptor oppose the beneficial actions of Ang-(1-7) at the Mas receptor for BRS regulation. Therefore, we examined Ang peptides, angiotensinogen (Aogen), and receptor expression in this brain region of exposed and control offspring of 0.5- and 1.8-years of age. Mas protein expression was significantly lower (>40%) in the dorsal medulla of BMX animals at both ages; however, AT1 receptor expression was not changed. BMX offspring exhibited a higher ratio of Ang II to Ang-(1-7) (2.30±0.36 versus 0.99±0.28; p<0.01) and Ang II to Ang I at 0.5-years. Although total Aogen was unchanged, Ang I-intact Aogen was lower in 0.5-year BMX animals (0.78±0.06 vs. 1.94±0.41; p<0.05) suggesting a greater degree of enzymatic processing of the precursor protein in exposed animals. We conclude that in utero BM exposure promotes an imbalance in the central RAS pathways of Ang II and Ang-(1-7) that may contribute to the elevated MAP and lower BRS in this model.

Sex differences in cardiac autonomic regulation and in repolarisation electrocardiography

The review summarises the present knowledge on the sex differences in cardiac autonomic regulations and in related aspects of electrocardiography with particular attention to myocardial repolarisation. Although some of the sex differences are far from fully established, multitude of observations show consistent differences between women and men. Despite more pronounced parasympathetic cardiac regulation, women have higher resting heart rate and lower baroreflex sensitivity. Of the electrocardiographic phenomena, women have longer QT interval duration, repolarisation sequence more synchronised with the inverse of the depolarisation sequence, and likely increased regional heterogeneity of myocardial repolarisation. Studies investigating the relationship of these sex disparities to hormonal differences led frequently to conflicting results. Although sex hormones seem to play a key role by influencing both autonomic tone and electrophysiological properties at the cellular level, neither the truly relevant hormones nor their detailed actions are known. Physiologic usefulness of the described sex differences is also unknown. The review suggests that new studies are needed to advance the understanding of the physiologic mechanisms responsible for these inequalities between women and men and provides key methodological suggestions that need to be followed in future research.

BAROREFLEX SENSITIVITY EVALUATION USING THE VOLTERRA–LAGUERRE TECHNIQUE

The short-term blood pressure can be adjusted through baroreflex control and the quantitative index of the regulation is baroreflex sensitivity (BRS). The noninvasive spontaneous BRS is mostly estimated by using linear model techniques either in the time domain or in the frequency domain. However, the complex physiological regulatory mechanism of blood pressure has nonlinear response characteristics. In this study, the nonlinear Volterra mathematical model and the orthogonal Laguerre function were used to obtain the BRS through the identified model parameters. The Volterra–Laguerre (VL) technique was used to analyze all samples in the EuroBaVar dataset. The results were compared with the BRS estimates obtained by the alpha coefficient (Alpha) technique and the sequence (SEQ) technique. The BRS values obtained with the VL technique in both supine and standing positions were significantly lower than those obtained through the Alpha and SEQ techniques (VL:9.8 ± 10.0, SEQ:19.9 ± 13.4 and Alpha:19.0 ± 15.0 ms/mmHg, in supine; VL:3.5 ± 2.3, SEQ:9.1 ± 5.8 and Alpha:7.7 ± 5.6 ms/mmHg, in standing). The VL technique was able to evaluate the BRS of all samples, even in patients with low BRS, in the EuroBaVar dataset.

Abstract 118: Fetal Betamethasone Exposure Enhances the Peptide Ratio of Angiotensin II to Angiotensin-(1-7) in the Dorsal Medulla of Adult Sheep

Betamethasone (BMS) is administered to women entering into early preterm labor to facilitate fetal lung development and decrease infant mortality; however, fetal steroid exposure may lead to deleterious consequences long term. In a sheep model of BMS exposure in utero, we show elevated mean arterial pressure (MAP) and decreased baroreflex sensitivity (BRS) for control of heart rate at 6- and 20-months (mo) of age. The changes in MAP and BRS are associated with alterations in components of both the circulating and intra-renal renin-angiotensin systems (RAS) that may ultimately shift the balance to the pro-hypertensive peptide, angiotensin (Ang) II. In the brain solitary tract nucleus, Ang II actions through the AT 1 receptor oppose the beneficial actions of Ang-(1-7) at the mas receptor for BRS regulation. We found decreased expression of the mas protein in the dorsal medulla of BMS-exposed animals at 6- and 20- months of age with no changes in the AT 1 receptor expression. To determine whether tissue Ang peptides may contribute to altered BRS, the present study utilized three selective radioimmunoassay (RIAs) to quantify Ang I, Ang II and Ang-(1-7) in the dorsal medulla of 6-mo old male sheep. Comparisons of tissue peptide concentrations were not significantly different between groups; however, BMS-exposed offspring have a significant increase in the ratio of Ang II to Ang-(1-7) (Control: 0.61 ± 0.11, BMS: 2.3 ± 0.62; p&lt;0.05). There was a significant increase in the ratio of Ang II to Ang I (Control: 0.66 ± 0.20, BMS: 2.35 ± 0.46), with no change in the ratio of Ang-(1-7) to Ang I. The altered peptide ratios potentially reflect a decrease in the ACE2 enzyme, which converts Ang II to Ang-(1-7), and an increase in ACE activity which concerts Ang I to Ang II. Future studies are required to determine enzymatic activity in dorsal medullary tissue, but data are consistent with previous observations on altered ACE and ACE2 in the circulation and kidney of BMS-exposed animals. We conclude that BMS-depedent fetal programming may influence the central RAS through alterations in the balance of Ang II and Ang-(1-7) that contribute to the elevated MAP, lower BRS, and altered renal function in this model. Support: HD0474584

Spontaneous baroreflex sensitivity: Prospective validation trial of a novel technique in survivors of acute myocardial infarction

Low baroreflex sensitivity (BRS) indicates poor prognosis after acute myocardial infarction. Noninvasive BRS assessment is complicated by nonstationarities and noise in electrocardiogram and pressure signals. Phase-rectified signal averaging is a novel signal processing technology overcoming these problems. To prospectively validate a BRS measure (baroreflex sensitivity assessed by means of phase-rectified signal averaging [BRS(PRSA)]) based on this technology. Nine hundred forty-one consecutive acute myocardial infarction survivors aged 80 years or younger in sinus rhythm were prospectively enrolled at 2 German university hospitals. All patients underwent 30-minute recordings of electrocardiogram and arterial blood pressures (Portapres; TNO-TPD Biomedical Instrumentation, Amsterdam, Netherlands) within the first 2 weeks after myocardial infarction. BRS(PRSA) was prospectively dichotomized at 1.58 ms/mm Hg. Primary end point was all-cause mortality at 5 years. Multivariable analyses included Global Registry of Acute Coronary Events score (dichotomized at ≥120), sex, BRS(PRSA), left ventricular ejection fraction (dichotomized at ≤35%), and diabetes mellitus. BRS(PRSA) was compared with 3 standard noninvasive BRS measures, that is, the sequence method, the transfer function method, and the correlation method. During follow-up, 72 patients (7.7%) died. BRS(PRSA) stratified the study population into a high-risk group of 405 patients (≤1.58 ms/mm Hg) with an estimated 5-year mortality of 14.2% and a low-risk group of 536 patients (>1.58 ms/mm Hg) with a 5-year mortality of 2.8% (P <.0001). On multivariable analysis, BRS(PRSA) ≤ 1.58 ms/mm Hg was associated with a hazard ratio of 3.1 (confidence interval 1.7-5.6; P = .001). Predictive power of BRS(PRSA) ≤ 1.58 ms/mm Hg was particularly strong in patients with a Global Registry of Acute Coronary Events score of ≥120 or with a left ventricular ejection fraction of ≤35%. BRS(PRSA) is a powerful and independent predictor of mortality in postinfarction patients especially when assessed in patients with a Global Registry of Acute Coronary Events score of ≥120 or a left ventricular ejection fraction of ≤35%.

The association between baroreflex sensitivity and blood pressure in children

Low baroreflex sensitivity (BRS) and heart rate variability (HRV) are associated with the pathogenesis of adult hypertension. However, limited information exists about the negative consequences of elevated childhood blood pressure (BP) and autonomic regulation. Additionally, there are developmental changes in autonomic regulation throughout puberty, yet studies have not appropriately accounted for this. The objective of this study was to investigate BRS and HRV in children with 2 different BP profiles, while controlling for the effects of maturation, age, sex, and body composition. A sample of 11- to 14-year-old participants were divided into 2 BP groups: high BP (HBP; ≥95th percentile; n = 21) and normal BP (NBP; <90th percentile; n = 85). Automated BP was measured at 2 time points. In lab-based testing, 5 min of beat-to-beat BP (Finapres) and R-R interval (RRI) were recorded (standard electrocardiogram) after 15 min of supine rest. Spectral indices were computed using fast Fourier transform, and transfer function analysis was used to compute BRS. High frequency (HF) and low frequency (LF) power spectral areas were set to 0.15-0.4 Hz and 0.04-0.15 Hz, respectively, and BRS was determined for the LF area. After adjustment for age, sex, maturation, and body composition, BRS (p = 0.04), LF (p = 0.008), and HF (p = 0.01) RRI variability, and RRI total power (p = 0.005) were lower in the HBP than in the NBP participants. As well, the LF/HF systolic BP variability ratio was higher in the HBP than in the NBP group (p = 0.03). Despite their young age, these children with high, yet not clinically hypertensive BP, display reduced autonomic regulation.

Baroreflex sensitivity and sleep-related breathing problems

“Sleep-related breathing problems” (SRBPs), as a term, encompasses a range of disorders of breathing during sleep. They are all characterized by airway obstruction and disturbance of normal breathing, and such disorders have been associated with altered autonomic function in adults. In this issue of The Journal, Coverdale et al, from the University of Western Ontario and the University of Waterloo, report a study of 106 adolescents where baroreflex sensitivity, a measure of autonomic function, was measured from blood pressure and ECG recordings. Teenagers with the highest scores for SRBP had the lowest baroreflex sensitivity, and this relationship was particularly noted in those with higher body mass index. These are new observations in this age group.Article page 610▶ “Sleep-related breathing problems” (SRBPs), as a term, encompasses a range of disorders of breathing during sleep. They are all characterized by airway obstruction and disturbance of normal breathing, and such disorders have been associated with altered autonomic function in adults. In this issue of The Journal, Coverdale et al, from the University of Western Ontario and the University of Waterloo, report a study of 106 adolescents where baroreflex sensitivity, a measure of autonomic function, was measured from blood pressure and ECG recordings. Teenagers with the highest scores for SRBP had the lowest baroreflex sensitivity, and this relationship was particularly noted in those with higher body mass index. These are new observations in this age group. Article page 610▶ Baroreflex Sensitivity is Associated with Sleep-Related Breathing Problems in AdolescentsThe Journal of PediatricsVol. 160Issue 4PreviewTo examine the relationship between sleep-related breathing problems (SRBPs) and baroreflex sensitivity (BRS) among adolescents and assesses whether body mass influences this relationship. Full-Text PDF

Baroreflex Sensitivity to Predict Malignant Middle Cerebral Artery Infarction

Hemicraniectomy has been shown to be an effective treatment of life-threatening edema (LTE) in malignant middle cerebral artery infarction when performed early. Identifying patients who will develop LTE is therefore imperative. We hypothesize that autonomic shift toward sympathetic dominance may relate to LTE formation. We aimed to investigate the predictive potential of baroreflex sensitivity (BRS) as a marker of autonomic balance for calculating the course of large middle cerebral artery infarction. Patients with middle cerebral artery infarction >2/3 of the territory and BRS measurement at admission were analyzed. BRS was estimated using the cross-correlational method. Demographic, clinical, and radiological data including stroke severity, infarct size, and basal ganglia involvement were recorded. Malignant course with LTE was defined as clinical deterioration and midline shift ≥5 mm in the first 48 hours. Eighteen (62.8%) patients developed LTE. Patients with LTE had lower BRS (2.3 versus 4.4 mm Hg/ms, P=0.007), larger infarcts (214 versus 144 mL, P=0.03), more frequent involvement of the basal ganglia (14 versus 4, P=0.03), and more often underwent thrombolysis combined with endovascular intervention (6 versus 0, P=0.04). In a multivariate model, BRS (OR, 0.36; CI, 0.14-0.93; P=0.03) and basal ganglia involvement (OR, 11.53; CI, 1.15-115.9; P=0.04) were independent predictors for LTE. This model correctly classified 86.2% of the malignant cases. Decreased BRS, mirroring sympathetic activation, and basal ganglia involvement were associated with development of malignant course with LTE in large middle cerebral artery infarction. The predictive relevance of our findings needs to be confirmed in further studies.

Relation between preoperative autonomic function and blood pressure change after tourniquet deflation during total knee replacement arthroplasty

BackgroundTourniquets are used to provide a bloodless surgical field for extremities. Hypotension due to vasodilation and bleeding after tourniquet deflation is a common event. Hemodynamic stability is modulated by the autonomic nervous system (ANS). Heart rate variability (HRV) is a sensitive method for detecting individuals who may be at risk of hemodynamic instability during general anesthesia. The purpose of this study was to investigate ANS function to predict hypotension after tourniquet deflation.MethodsEighty-six patients who underwent total knee replacement arthroplasty (TKRA) were studied. HRV, systolic blood pressure variability (SBPV) and baroreflex sensitivity (BRS) were analyzed. We assigned two groups depending on the lowest systolic blood pressure (SBP) or mean BP (MBP) after tourniquet release (Group H; SBP < 80 mmHg or MBP < 60 mmHg, Group S; SBP > 80 mmHg and MBP > 60 mmHg).ResultsFifteen patients developed severe hypotension and ten patients were treated with ephedrine. Of the parameters of HRV, SBPV, and BRS, only BRSSEQ was significant being low in Group H. BRS and high-frequency SBPV were correlated with the degree of MBP change after tourniquet deflation.ConclusionsPreoperative low BRS is associated with hypotension after tourniquet deflation, suggesting the importance of baroreflex regulation for intraoperative hemodynamic stability.

Preterm Birth Alters the Maturation of Baroreflex Sensitivity in Sleeping Infants

Impaired blood pressure (BP) control may underpin the increased incidence of the sudden infant death syndrome (SIDS) in preterm infants. This study aimed to examine the effects of preterm birth, postnatal age, and sleep state on BP control by measuring baroreflex sensitivity (BRS) across the first 6 months of term-corrected age (CA), when SIDS risk is greatest. Preterm (n = 25) and term (n = 31) infants were studied longitudinally at 2 to 4 weeks, 2 to 3 months, and 5 to 6 months CA using daytime polysomnography. BP was recorded during quiet (QS) and active (AS) sleep using a photoplethysmographic cuff placed around the infant's wrist (Finometer [FMS, Finapres Medical Systems, Amsterdam, Netherlands]). BRS (milliseconds/mm Hg) was assessed in 1- to 2-minute epochs using cross-spectral analysis. In preterm infants, postnatal age had no significant effect on BRS within either QS or AS. This was in contrast to the maturational increase in QS observed in term infants. Compared with term infants, BRS of preterm infants was 38% higher at 2 to 4 weeks CA and 29% lower at 5 to 6 months CA during QS (P <.05). Comparing sleep states, BRS of preterm infants was 26% lower in QS compared with AS at 2 to 3 months CA (P <.05). Preterm birth impairs the normal maturational increase in BRS, resulting in a substantial reduction in BRS at 5 to 6 months CA during QS. Lower BRS during QS compared with AS at 2 to 3 months CA may place preterm infants at an increased risk for cardiovascular instability at this age of peak incidence of SIDS.

Association of Cardiac Baroreflex Sensitivity with Blood Pressure Transients: Influence of Sex and Menopausal Status

The magnitude of decrease in blood pressure (BP) during a vasoactive drug bolus may be associated with the calculated baroreflex sensitivity (BRS). The purpose of the present study was to evaluate whether sympathetic and/or cardiac BRS relates to the extent of change in BP and whether this was altered by sex hormones. Fifty-one young women (27 ± 1 years), 14 older women (58 ± 1 years), and 36 young men (27 ± 1 years) were studied. Heart rate, BP, and muscle sympathetic nerve activity (MSNA) were monitored. Sympathetic BRS was analyzed using the slope of the MSNA-diastolic blood pressure (DBP) relationship and cardiac BRS was analyzed using the R–R interval-systolic blood pressure (SBP) relationship. Young women and men had similar mean arterial pressures (MAP, 91 ± 1 vs. 90 ± 1 mmHg), cardiac BRS (19 ± 1 vs. 21 ± 2 ms/mmHg), and sympathetic BRS (−6 ± 1 vs. −7 ± 1 AU/beat/mmHg), respectively. Older women had higher MAP (104 ± 4 mmHg, p < 0.05) and lower cardiac BRS (7 ± 1 ms/mmHg, p < 0.05), but similar sympathetic BRS (−8 ± 1 AU/beat/mmHg). There was no association between BP transients with either cardiac or sympathetic BRS in young women. In the older women, the drop in SBP, DBP, and MAP were associated with cardiac BRS (r = 0.60, r = 0.59, and r = 0.70, respectively; p < 0.05), but not sympathetic BRS. The decrease in SBP was positively related to cardiac BRS in young men (r = 0.41; p < 0.05). However, there was no relationship between the decrease in BP and sympathetic BRS. This indicates that older women and young men with low cardiac BRS have larger transients in BP during nitroprusside. This suggests a more prominent role for cardiac (as opposed to sympathetic) BRS in responding to acute BP changes in young men and older women. The fact that these relationships do not exist in young women suggest that the female sex hormones influence baroreflex responses.

Cerebral artery remodeling in stroke‐prone spontaneously hypertensive rats

Stroke is a major cause of disability and presents a serious and growing threat to public health [1]. Epidemiological studies have shown that stroke is the second leading cause of death in the world [2]. Among the risk factors for stroke, hypertension is the most powerful modifiable factor and the second most powerful risk factor after age [3–5]. Hypertension eventually results in target organ damage such as myocardial hypertrophy and artery remodeling [6]. Over 70% of stroke cases can be attributed to hypertension [7]. Arterial baroreflex (ABR) is one of the most important physiological mechanisms controlling blood pressure (BP) regulation. Its function, manifested as baroreflex sensitivity (BRS), correlates to the degree of end-organ damage in spontaneously hypertensive rats (SHR), a genetic model for hypertension [8]. Stroke-prone SHR (SHR-SP) is a substrain of SHR that exhibits much higher incidence of stroke compared with age-matched SHR. The mechanisms underlying such a difference remain to be fully understood. Signs of stroke, including movement of limbs, respiration, diet, fur and consciousness, were observed in 25 SHR (male 13, female 12) and 26 SHR-SP (male 13, female 13) at the age of 28 weeks. The neuroethology assessment was performed by using the Zea-Longa score (maximum score: 5, higher score indicates more severe neurological impairment). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and BRS were determined in conscious rats as previously described [9]. Serial transverse paraffin sections (5 μm thick separated by 100 μm) were prepared using routine techniques. Ten slides were stained with hematoxylin-eosin and observed under light microscope. Structure of cerebral arteries with external diameter of 0.07–0.09 mm and 0.7–0.9 mm were evaluated with a SDK-2000 system for image analysis. Data are expressed as mean ± SD. Differences between the two groups were evaluated by unpaired t-test. Stroke incidence was analyzed with chi-square test. The relationships of SBP and BRS with wall thickness of cerebral arteries were assessed by univariate regression analysis. P < 0.05 was considered statistically significant. The behavior of each rat was observed separately. Positive signs occurred in 9 of the 26 SHR-SP (incidence: 34.62%), and none out of the 25 SHR (Figure 1A). The Zea-Longa score was significantly higher in SHR-SP (Figure 1B, P < 0.001 vs. SHR). SBP and DBP were significantly higher in SHR-SP (Figure 1C, P < 0.01 vs. SHR). BRS was significantly lower in SHR-SP (Figure 1D, P < 0.01 vs. SHR). Comparison of incidence of stroke, neuroethology assessment, BP and BRS between SHR and SHR-SP. 28-week-old SHR (n = 25, male 13, female 12) and SHR-SP (n = 26, male 13, female 13) were used. (A) Positive symptoms occurred in 9 of 26 SHR-SP, with a stroke incidence of 34.62%, and no animal with positive symptom was found in SHR. (B) Zea-Longa score of SHR-SP was significantly higher than that of SHR. (C) BP of SHR-SP was significant higher than that of SHR. (D) BRS of SHR-SP was significantly lower than that of SHR. **P < 0.01, ***P < 0.001 versus SHR. There was no significant difference in wall thickness, lumen diameter, wall-to-lumen ratio and wall cross sectional area between SHR-SP and SHR in the cerebral arteries with external diameter of 0.07–0.09 mm (Table 1). For cerebral arteries with external diameter of 0.7–0.9 mm, wall thickness, wall-to-lumen ratio and wall cross sectional area were significantly larger (P < 0.001), and the lumen diameter was significantly smaller (P < 0.05) in SHR-SP compared with that in SHR. In SHR-SP, the wall thickness was positively correlated with SBP (r = 0.366, P < 0.05), and negatively correlated with BRS (r = 0.596, P < 0.01). ABR dysfunction has been repeatedly reported to be present in acute stroke [10]. A recent study from this laboratory in hypertensive rats indicated that BRS is an independent predictor for stroke [9]. Results from the current study showed that hypertension and ABR dysfunction were more severe in SHR-SP than in SHR. Consistent with the relatively high BP and low BRS in SHR-SP, cerebral artery remodeling, e.g., increased vascular wall thickness and decreased lumen diameter, was also more pronounced in SHR-SP. In conclusion, cerebral artery remodeling may represent a key pathological feature that makes SHR-SP much more vulnerable to stroke than SHR.

Abstract 9687: Vagal Reflexes as a Simple Clinical Tool to Stratify Risk Among LQT1 Patients

Background We demonstrated that lower baroreflex sensitivity (BRS) values can identify Long QT Syndrome 1(LQT1) patients at lower risk for life-threatening arrhythmias, suggesting a protective role of “blunted” autonomic responses. However, the complexities of the phenylephrine method to assess BRS have limited its use for risk stratification in clinical practice. Objectives To identify an easily quantifiable marker of reflex vagal activation that might perform as well as BRS in predicting a differential risk for life-threatening arrhythmias in LQT1 patients. Specifically, to test the predictive value of heart rate (HR) recovery during the first minute after cessation of an exercise stress test. Methods In a South African LQT1 founder population segregating KCNQ1-A341V, 44 mutation carriers (MCs) underwent an exercise stress test and a phenylephrine test off-β-blockers. The HR decrease during the first minute of recovery from the peak of exercise (Δ 1min-rec ) was measured and subsequently correlated with BRS values among symptomatic (syncope, cardiac arrest, sudden death) and asymptomatic patients. Results Asymptomatic MCs had a smaller decrease in HR during the first minute of recovery from peak exercise (Δ 1min-rec ) than symptomatic MCs (13±5 vs 19±7 bpm, p&lt; 0.05). A Δ 1min-rec &lt;15 bpm, which corresponds to the first tertile of its distribution, predicted a much lower probability of being symptomatic (OR 0.13, 95%CI 0.028-0.63, p&lt;0.05). The Δ 1min-rec values were significantly correlated with BRS values (r=0.64, p=0.001). Both tests performed similarly and quite accurately in discriminating between MCs with or without cardiac events (AUC 0.77 and 0.80). Conclusions LQT1 patients are at risk for life-threatening arrhythmias especially in association with rapid HR changes in either direction. Blunted autonomic responses, identified by lower values of BRS and - as vagal reflexes are concerned - by smaller HR reductions at the end of exercise, can usefully contribute to their risk stratification in a novel, simple, and inexpensive way.

Baroreflex Sensitivity is Associated with Sleep-Related Breathing Problems in Adolescents

To examine the relationship between sleep-related breathing problems (SRBPs) and baroreflex sensitivity (BRS) among adolescents and assesses whether body mass influences this relationship. SRBPs were assessed in 106 adolescents aged 11-14 years using the Pediatric Sleep Questionnaire. Body mass index (BMI) was calculated, and 5 minutes of continuous beat-to-beat blood pressure (Finapres) and R-R interval were recorded (standard electrocardiogram) after 15 minutes of supine rest. Spectral indices were computed using fast Fourier transform, and transfer function analysis was used to compute BRS. Regression analyses indicate an interaction between BMI and SRBPs (b=-.151, P=.015) on BRS. Graphing the interaction showed that those with higher SRBP scores had lower BRS but that this effect was stronger for those with higher BMI. Adolescents with elevated SRBP scores had lower BRS. In addition, higher BMI amplified the risk of higher SRBP scores on BRS.

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.

Baroreflex Sensitivity and Its Response to Deep Breathing Predict Increase in Blood Pressure in Type 1 Diabetes in a 5-Year Follow-Up

OBJECTIVEWe have recently demonstrated that early autonomic dysfunction, defined as low baroreflex sensitivity (BRS), could be functional and reversible. However, potential temporal changes in BRS have not yet been addressed by longitudinal studies in type 1 diabetes. Moreover, it is not known whether low BRS predisposes to hypertension or other nonfatal diabetes complications.RESEARCH DESIGN AND METHODSWe conducted a 5-year prospective study including 80 patients with type 1 diabetes. We measured ambulatory blood pressure and autonomic function tests. BRS was assessed by six different methods during spontaneous, controlled, and slow deep breathing at baseline and follow-up.RESULTSSpontaneous BRS declined over time (BRSaverage 16.2 ± 0.8 vs. 13.2 ± 0.8 ms/mmHg; P < 0.01), but the change was not significant when adjusted for time of follow-up. Low BRS at baseline did not progress to cardiac autonomic neuropathy but predicted an increase in the nighttime systolic blood pressure (BRSaverage r = −0.37; P < 0.05). Additionally, BRS response to deep breathing at baseline predicted an increase in 24-h ambulatory blood pressure (BRS-αLF r = 0.323–0.346; P < 0.05).CONCLUSIONSThe decline in spontaneous BRS over time in patients with type 1 diabetes seems to be due to normal aging, which supports a functional etiology behind early autonomic derangements. Decreased resting BRS and the magnitude of improvement by deep breathing may be due to sympathovagal imbalance, a well-known mechanism in the development of hypertension. Early interventions aiming to reduce sympathetic overactivity in patients with low BRS might delay the development of hypertension.