Cardiac Baroreceptor Sensitivity Research Articles

Repetitive bout of controlled soccer heading does not alter heart rate variability metrics: A preliminary investigation.

There is elevated unease regarding how repetitive head impacts, such as those associated with soccer heading, contribute to alterations in brain function. This study examined the extent heart rate variability (HRV) and cardiac baroreceptor sensitivity (BRS) metrics are altered immediately following an acute bout of soccer heading. Seven male elite soccer players (24.1 ± 1.5 years) completed 40 successful soccer headers in 20-min. The headers were performed under controlled circumstances using a soccer ball launcher located 25 meters away and using an initial ball velocity of 77.5 ± 3.7 km/h (heading condition). An accelerometer (xPatch) on the right mastoid process quantified linear/rotational head accelerations. Participants also completed sham (body contact) and control (non-contact) sessions. A three-lead ECG and finger photoplethysmography characterized short-term spontaneous HRV/cardiac BRS, before and after each condition. The SCAT3 indexed symptom scores pre-post exposures to all three conditions. During the heading condition, cumulative linear and rotational accelerations experienced were 1,574 ± 97.9 g and 313,761 ± 23,966 rad/s2, respectively. Heart rate trended toward an increase from pre- to post-heading (p = 0.063), however HRV metrics in the time-domain (ps > 0.260) and frequency-domain (ps > 0.327) as well as cardiac BRS (ps > 0.144) were not significantly changed following all three conditions. Following the heading condition, SCAT3 symptom severity increased (p = 0.030) with a trend for symptom score augmentation (p = 0.078) compared to control and sham. Whereas, symptoms as measured by the SCAT3 were induced following an acute bout of controlled soccer heading, these preliminary findings indicate they were not accompanied by alterations to autonomic function. Ultimately, this demonstrates further research is needed to understand the physiological underpinnings of alterations in brain function occurring immediately after a bout of soccer heading and how these may, over time, contribute to long-term neurological impairments.

The reciprocal relationship between cardiac baroreceptor sensitivity and cerebral autoregulation during simulated hemorrhage in humans.

A reciprocal relationship between the baroreflex and cerebral autoregulation (CA) has been demonstrated at rest and in response to acute hypotension. We hypothesized that the reciprocal relationship between cardiac baroreflex sensitivity (BRS) and CA would be maintained during sustained central hypovolemia induced by lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n=51; 23F/28M) completed a LBNP protocol to presyncope. Subjects were classified as high tolerant (HT; completion of -60mmHg LBNP stage, ≥20-min) or low tolerant (LT; did not complete -60mmHg LBNP stage, <20-min). R-R intervals (RRI), systolic arterial pressure (SAP), mean arterial pressure (MAP), and middle cerebral artery velocity (MCAv) were measured continuously. Cardiac BRS was calculated in the time domain (ΔHR/ΔSAP) and frequency domain (RRI-SAP low frequency (LF) transfer function gain), and CA was calculated in the time domain (ΔMCAv/ΔMAP) and frequency domain (MAP-mean MCAv LF transfer function gain). There was a moderate relationship between cardiac BRS and CA for the group of 51 subjects in both the time (R=-0.54, P<0.0001) and frequency (R=0.61, P<0.001) domains; there was a stronger relationship in the HT group (R=0.73) compared to the LT group (R=0.31) in the frequency domain (P=0.08), but no difference between groups in the time domain (HT: R=-0.73 vs. LT: R=-0.63; P=0.27). These findings suggest that an interaction between BRS and CA may be an important compensatory mechanism that contributes to tolerance to simulated hemorrhage in young healthy adults.

Post-Acute Effect of SARS-CoV-2 Infection on the Cardiac Autonomic Function.

BackgroundRecent studies reported a long-lasting effect of COVID-19 infection that extends beyond the active disease and disrupts various body systems besides the respiratory system. The current study aims to investigate the post-acute effect of SARS-CoV-2 infection on cardiovascular autonomic activity, reactivity and sensitivity in patients who had the infection at least 3 months before.MethodsThis was a comparative cross-sectional observational study. Fifty-nine subjects were allocated into two groups, controls (n=31), who had no history of positive COVID-19 infection, and the post-COVID patients (n=28) who were recruited 3 to 8 months after testing positive for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR). Baseline cardiovascular autonomic activity was evaluated through recording of baseline heart rate variability (HRV), autonomic reactivity was determined through standard cardiovascular autonomic reflex tests (CART), and cardiac autonomic sensitivity was assessed through cardiac baroreceptor sensitivity (cBRS).ResultsHigher incidence of orthostatic hypotension was observed in post-COVID patients compared to controls (39.3% and 3.2%, respectively, p <0.001). Additionally, significantly reduced handgrip test, and heart rate response to head-up tilt was illustrated in the post-COVID group (p <0.001). About 85.7% of post-COVID participants had at least one abnormal cardiovascular reflex test (CART) compared to the control group (p <0.001). Although HRV parameters (TP, LF, HF, SDRR, RMSSD, pRR50), and the cBRS were numerically lower in the post-COVID-19 group, this did not reach the level of significance.ConclusionThe results of the present study are suggestive of altered cardiovascular reactivity in post-acute COVID patients and demand further investigation and longer term follow up.

Acute cardiac autonomic and haemodynamic responses to leg and arm isometric exercise.

Acute cardiovascular responses following a single session of isometric exercise (IE) have been shown to predict chronic adaptations in blood pressure (BP) regulation. It was hypothesised that exercises which recruit more muscle mass induce greater reductions in BP compared to exercises using smaller muscle mass. To test this hypothesis, the current study aimed to compare the acute haemodynamic and autonomic responses to a single session of isometric wall squat (IWS) and isometric handgrip (IHG) training. Twenty-six sedentary participants performed a single IWS and IHG session in a randomised cross-over design, with training composed of 4 × 2-min contractions, with 2-min rest, at 95 HRpeak and 30% MVC respectively. Haemodynamic and cardiac autonomic variables were recorded pre, during, immediately post, and 1-h post-exercise, with the change from baseline for each variable used for comparative analysis. During IWS exercise, there was a significantly greater increase in systolic BP (P < 0.001), diastolic BP (P < 0.001), mean BP (P < 0.001), heart rate (P < 0.001), and cardiac output (P < 0.001), and a contrasting decrease in baroreflex effectiveness index (BEI) and cardiac baroreceptor sensitivity (cBRS). In the 10-min recovery period following IWS exercise, there was a significantly greater reduction in systolic BP (P = 0.005), diastolic BP (P = 0.006), mean BP (P = 0.003), total peripheral resistance (TPR) (P < 0.001), BEI (P = 0.003), and power spectral density (PSD-RRI) (P < 0.001). There were no differences in any variables between conditions 1-h post exercise. Isometric wall squat exercise involving larger muscle mass is associated with a significantly greater post-exercise hypotensive response during a 10-min recovery window compared to smaller muscle mass IHG exercise. The significantly greater reduction in TPR may be an important mechanism for the differences in BP response.

Long-term heart transplant recipients: heart rate-related effects on augmented transfer function coherence during repeated squat-stand maneuvers in males.

Previous research has highlighted that squat-stand maneuvers (SSMs) augment coherence values within the cerebral pressure-flow relationship to ∼0.99. However, it is not fully elucidated if mean arterial pressure (MAP) leads to this physiological entrainment independently, or if heart rate (HR) and/or the partial pressure of carbon dioxide (Pco2) also have contributing influences. A 2:1 control-to-case model was used in the present investigation [participant number (n) = 40; n = 16 age-matched (AM); n = 16 donor control (DM); n = 8 heart transplant recipients (HTRs)]. The latter group was used to mechanistically isolate the extent to which HR influences the cerebral pressure-flow relationship. Participants completed 5 min of squat-stand maneuvers at 0.05 Hz (10 s) and 0.10 Hz (5 s). Linear transfer function analysis (TFA) examined the relationship between different physiological inputs (i.e., MAP, HR, and Pco2) and output [cerebral blood velocity (CBV)] during SSM; and cardiac baroreceptor sensitivity (BRS). Compared with DM, cardiac BRS was reduced in AM (P < 0.001), which was further reduced in HTR (P < 0.045). In addition, during the SSM, HR was elevated in HTR compared with both control groups (P < 0.001), but all groups had near-maximal coherence metrics ≥0.98 at 0.05 Hz and ≥0.99 at 0.10 Hz (P ≥ 0.399). In contrast, the mean HR-CBV/Pco2-CBV relationships ranged from 0.38 (HTR) to 0.81 (DM). Despite near abolishment of BRS and blunted HR following heart transplantation, long-term HTR exhibited near-maximal coherence within the MAP-CBV relationship, comparable with AM and DM. Therefore, these results show that the augmented coherence with SSM is driven by blood pressure, whereas elevations in TFA coherence as a result of HR contribution are likely correlational in nature.

The Reciprocal Relationship Between Cardiac Baroreceptor Sensitivity and Cerebral Autoregulation During Simulated Hemorrhage in Humans

Tolerance to reduced central blood volume (e.g., via hemorrhage) depends upon cardiovascular and cerebrovascular mediated compensatory mechanisms to preserve cerebral perfusion. Prior studies have demonstrated a reciprocal relationship between the arterial baroreflex and cerebral autoregulation (CA) at rest and in response to acute hypotension. It is unknown if this reciprocal relationship persists during progressive and sustained hypotension simulating hemorrhage. We hypothesized that the reciprocal relationship between cardiac baroreceptor sensitivity (BRS) and CA would be maintained during a simulated hemorrhage induced by maximal lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n=51; 23F/28M, 26 ± 4 y) completed a step-wise LBNP protocol until the onset of presyncope. Subjects were classified as high tolerant (HT) if they completed at least the -60 mmHg stage of LBNP (≥ 20-min), and low tolerant (LT) if they became presyncopal prior to completing the -60 mmHg stage of LBNP (< 20-min), as previously defined by our group. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), and middle cerebral artery velocity (MCAv) were measured continuously. The absolute change from baseline to presyncope (Δ) was calculated for each variable. Cardiac BRS was calculated as ΔHR divided by ΔMAP, and CA was calculated as ΔMCAv divided by ΔMAP. The relationship between BRS and CA was assessed with Pearson's correlation coefficients for the entire group of 51 subjects, and within the HT and LT sub-groups. Absolute change values for the hemodynamic responses were also compared between the two tolerance groups. By design, tolerance to LBNP was different between the groups (HT (n=30): 1775 ± 225 s vs. LT (n=21): 1184 ± 253 s; P<0.0001). Accordingly, HT subjects demonstrated a greater ΔSV (HT: -51 ± 17 ml vs. LT: -41 ± 13 ml; P=0.03) and a greater ΔHR (HT: +56 ± 17 bpm vs. LT: +34 ± 20 bpm; P<0.0001) in response to maximal LBNP. Interestingly, ΔMAP (HT: -18 ± 7 mmHg vs. LT: -19 ± 9 mmHg; P=0.51), ΔMCAv (HT: -17 ± 8 cm/s vs. LT: -19 ± 10 cm/s; P=0.52), BRS (HT: 4 ± 3 bpm/mmHg vs. LT: 3 ± 4 bpm/mmHg; P=0.24), and CA (HT: 1.2 ± 0.9 cm/s.mmHg-1 vs. LT: 1.5 ± 1.8 cm/s.mmHg-1; P=0.45) were similar between HT and LT subjects. In support of our hypothesis, there was a strong reciprocal relationship (R=0.77; P<0.0001) between BRS and CA in the group of 51 subjects. When independently assessing this relationship within each tolerance group, however, there was a stronger relationship in LT subjects (R=0.94; P<0.0001) compared to HT subjects (R=0.57; P<0.001). In support of our hypothesis, the reciprocal relationship between cardiac BRS and CA was maintained during sustained and progressive hypotension, but this relationship was stronger in subjects with lower tolerance to this stress. These findings suggest that despite a strong overall relationship in the interaction between BRS and CA, it may not be a primary compensatory mechanism that dictates tolerance to simulated hemorrhage in young healthy adults.

Effects of renal denervation on cardiovascular, metabolic and renal functions in streptozotocin-induced diabetic rats

Diabetes promotes renal sympathetic hyperactivity, autonomic imbalance, and cardiovascular and renal dysfunction. Bilateral renal denervation (BRD) has emerged as a treatment for diabetes; however, the mechanisms that underlie the beneficial effects of BRD are unknown. AimsThe present study evaluated the effects of BRD on autonomic, cardiovascular, metabolic, and renal function in streptozotocin-diabetic rats. Main methodsWistar rats were separated into three experimental groups: control (CTR), diabetic (DM), and diabetic that underwent BRD (DM BRD). BRD was performed two weeks after STZ-diabetes induction, the experiments were performed four weeks after DM induction. This study evaluated sympathetic vasomotor nerve activity in different territories (renal, lumbar and splanchnic), arterial baroreceptor reflex, metabolic and renal function. Key findingsBRD significantly reduced glycemia, glycosuria, albuminuria, and SGLT2 gene expression in the kidney in DM rats. Renal sympathetic nerve activity (rSNA) was significantly increased and splanchnic sympathetic nerve activity (sSNA) was significantly decreased in DM rats, without changes in lumbar sympathetic nerve activity (lSNA). BRD was able to normalize sSNA and significantly increase lSNA in DM rats compared to control rats. Additionally, cardiac baroreceptor sensitivity was impaired in DM rats, and BRD significantly improved baroreflex sensitivity. SignificanceOur data suggest that renal nerves play an important role in autonomic, cardiovascular, and renal dysfunction in STZ-DM rats. Thus, sympathetic renal hyperactivity should be considered a possible therapeutic target in diabetic patients.

Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices.

Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation. Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30o and 60o. Heart rate and BP were monitored during cardiopulmonary exercise testing. Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing. Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.

Effects of high-intensity intervals and moderate-intensity exercise on baroreceptor sensitivity and heart rate variability during recovery.

Numerous studies have examined heart rate variability (HRV) and cardiac baroreceptor sensitivity (BRS) variables during recovery both acutely (under 3 h) and long-term (24, 48, and 72 h) postexercise. However, there is little literature examining HRV and BRS measures between these timepoints. Spontaneous short-term HRV and cardiac BRS measures were collected in 9 participants before and at zero, 1, 2, 4, 6, and 8 h after 3 separate conditions: moderate-intensity continuous exercise (MICE; 45 min at 50% heart rate reserve), high-intensity interval exercise (HIIE; 25 min including ten 1-min intervals at 85% heart rate reserve), and control (30 min quiet rest). HRV measures in the time domain were only affected immediately following HIIE and MICE at hour zero (all p < 0.043), whereas frequency-domain metrics were unaltered (all p > 0.102). These measures were highly consistent across the control day (all p > 0.420). Cardiac BRS was assessed via low-frequency (LF) gain, and revealed reductions following HIIE at hour zero (p < 0.012). Cardiac BRS LF gain remained consistent following MICE and control interventions (all p > 0.280). The common practice of waiting 12 to 24 h is overly conservative as the current findings demonstrate measures return to baseline at ∼60 min after exercise. Moreover, these metrics demonstrated high levels of within- and between-day reliability. Novelty Previously a 12-h minimum restriction from exercise was required before participation in HRV/BRS studies. Recovery from moderate-intensity exercise for HRV and BRS metrics was <60 min; whereas, high-intensity intervals led to alterations for approximately 60 min. Spontaneous HRV and cardiac BRS demonstrated high levels of within-day reproducibility.

Autonomic Abnormalities in Patients With Primary Sjogren's Syndrome - Preliminary Results.

Primary Sjögren’s syndrome (pSS) is an autoimmune disease affecting exocrine glands and extra-glandular organs. There are conflicting reports on the presence of autonomic dysfunction in pSS and no data are available on the functional status of sympathetic outflow to the vessels and baroreceptor [baroreflex sensitivity (BRS)] control mechanisms. We investigated the cardiac (cBRS) and sympathetic (sBRS) baroreceptor modulation in both time and frequency domains and the cardiovascular autonomic profile in pSS patients compared to healthy controls. Autonomic symptoms were quantified by the Composite Autonomic Symptom Scale (COMPASS31) three-item questionnaire. The EULAR Sjogren’s syndrome patient reported index (ESSPRI) questionnaire evaluated the magnitude of pSS clinical symptoms, i.e., fatigue, pain, and sicca symptoms. Electrocardiogram, beat-by-beat arterial pressure (AP) and respiratory activity were continuously recorded in 17 pSS patients and 16 healthy controls, while supine and during 75° head-up tilt. In seven patients and seven controls, muscle sympathetic nerve activity (MSNA) was measured. Spectrum analysis of RR variability provided markers of cardiac vagal modulation (HFRR nu) and sympatho-vagal balance [low frequency (LF)/high frequency (HF)]. The power of LF (0.1 Hz) oscillations of systolic arterial pressure (SAP) variability (LFSAP) evaluated the vasomotor response to sympathetic stimulation. Compared to controls, pSS patients scored higher in total COMPASS31 (p < 0.0001) and all ESSPRI subdomains (fatigue, p = 0.005; pain, p = 0.0057; dryness, p < 0.0001). Abnormal scialometry (<1.5 ml/15 min) and Schirmer tests (<5 mm/5 min) were found in pSS patients and salivary flow rate was negatively associated with ESSPRI dryness (p = 0.0014). While supine, pSS patients had lower SEQcBRS index of cardiac baroreceptor sensitivity, higher HFRRnu (p = 0.021), lower LF/HF (p = 0.007), and greater MSNA (p = 0.038) than controls. No differences were observed in LFSAP between groups. During orthostatic challenge, although LFSAP increased similarly in both groups, MSNA was greater in pSS patients (p = 0.003). At rest pSS patients showed lower cBR control and greater parasympathetic modulation. Furthermore, greater sympathetic nerve activity was observed in pSS patients while supine and in response to gravitational challenge. We hypothesized that such enhanced sympathetic vasoconstrictor activity might reflect an attempt to maintain blood pressure in a setting of likely reduced vascular responsiveness.

Role of infarct location and pre-existing depression on cardiac baroreceptor sensitivity in subacute ischemic stroke.

Reduced cardiac baroreceptor sensitivity (BRS) after acute stroke is associated with worse outcome. The underlying mechanisms of reduced BRS are unclear. We evaluated cross correlation BRS (xBRS) in 184 patients with suspected acute ischemic stroke within 72h of symptom onset. Among these patients, 22 had a transient ischemic attack (TIA) and 27 had a stroke mimic. Sixty-four age- and sex-matched ambulant control subjects without stroke were included. Compared with controls, xBRS was significantly lower in patients with ischemic stroke, TIA, and stroke mimics (4.6, 4.7, and 4.4, respectively, vs 6.6, p<0.01). There was no difference in xBRS between right and left hemispheric infarctions (4.3 vs 4.9, p=0.144), right and left insular infarctions (4.5 vs 5.3, p = 0.286), and insular infarction vs non-insular infarctions (4.7 vs 4.5, p=0.996). Stroke patients with pre-existing depression/use of antidepressant medication had lower xBRS values than stroke patients with normal mental health (2.9 vs 4.8, p<0.05). Control patients with depression also had lower xBRS compared to controls without depression (3.4 vs 5.9, p<0.01). Our results suggest that decreased xBRS in the subacute phase after stroke is not associated with infarct localization. We found preliminary evidence for an association between pre-existing depression and use of antidepressant medication, and decreased BRS.

Relationship between cerebral blood flow and blood pressure in long-term heart transplant recipients.

Heart transplant recipients are at an increased risk for cerebral hemorrhage and ischemic stroke; yet, the exact mechanism for this derangement remains unclear. We hypothesized that alterations in cerebrovascular regulation is principally involved. To test this hypothesis, we studied cerebral pressure-flow dynamics in 8 clinically stable male heart transplant recipients (62±8 years of age and 9±7 years post transplant, mean±SD), 9 male age-matched controls (63±8 years), and 10 male donor controls (27±5 years). To increase blood pressure variability and improve assessment of the pressure-flow dynamics, subjects performed squat-stand maneuvers at 0.05 and 0.10 Hz. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal carbon dioxide were continuously measured during 5 minutes of seated rest and throughout the squat-stand maneuvers. Cardiac baroreceptor sensitivity gain and cerebral pressure-flow responses were assessed with linear transfer function analysis. Heart transplant recipients had reductions in R-R interval power and baroreceptor sensitivity low frequency gain (P<0.01) compared with both control groups; however, these changes were unrelated to transfer function metrics. Thus, in contrast to our hypothesis, the increased risk of cerebrovascular complication after heart transplantation does not seem to be related to alterations in cerebral pressure-flow dynamics. Future research is, therefore, warranted.

Are baroreflex events detected by invasive and non‐invasive techniques coincident?

Cardiac baroreceptor sensitivity, a prognostic indicator for a range of diseases, such as myocardial infarction and stroke, may be estimated from spontaneous fluctuations of arterial blood pressure (BP) and heart rate using sequence analysis. We tested the hypothesis that BP values recorded with the non-invasive Finapres device do not always produce sequences coincident with sequences detected from central BP measurements. Finapres recordings of resting BP in the finger, ascending aorta (Millar catheter-tip transducer) and ECG were obtained from 34 patients undergoing coronary angioplasty, including 24 patients treated with betablockers. Coincidence of baroreflex sensitivity (BRS) sequences was expressed by the sensitivity of the Finapres to detect a simultaneously occurring sequence in aortic pressure. The influence of different criteria to detect and accept sequences from beat-to-beat values of systolic BP (SBP) and cardiac interval (RRi) on the Finapres sensitivity was also assessed. The Finapres was able to detect 70.7% of all three beat intra-arterial sequences when the selection criteria was based on the correlation coefficient between SBP and RRi (>0.85), but decreased to 27.5% when the P-value of the linear regression was limited to 0.05. Changing the thresholds for minimum changes in SBP and RRi also had significant effects on sensitivity, as well as in the corresponding values of BRS. Significant differences in BRS were obtained between invasive and non-invasive estimates, but there was no difference between non-invasive estimates calculated from coincident and non-coincident sequences. Non-invasive, compared with intra-arterial estimates of BRS by sequence analysis are not influenced by coincidence of sequences if acceptance of sequences is based on the correlation coefficient criteria (>0.85).

Influence of non-invasive measurements of arterial blood pressure in frequency and time-domain estimates of cardiac baroreflex sensitivity

To compare estimates of cardiac baroreceptor sensitivity (BRS) obtained by the Finapres device and from the direct measurement of arterial blood pressure (ABP) values from the ascending aorta, using both spectral analysis and sequence analysis. A cohort study of 45 coronary artery disease patients undergoing routine percutaneous coronary procedures. Continuous supine recordings of resting ABP in the finger (Finapres), ascending aorta (Millar catheter-tip transducer) and electrocardiogram were obtained. Beat-to-beat values of systolic ABP (Finapres and aortic) and R-R interval were used to estimate the cardiac BRS from spontaneous sequences and by spectral analysis, using the alpha index for the low-frequency band (0.05-0.15 Hz). The influence of beta-blockers on BRS estimates was also investigated. No significant difference was observed between estimates of BRS derived from the Finapres (BRSFIN) and aortic ABP (BRSAO) by the spectral analysis method (Finapres bias 0.30 +/- 2.52 ms/mmHg). For sequence analysis, BRSFIN was significantly higher than BRSAO (7.80 +/- 4.52 versus 6.44 +/- 3.46 ms/mmHg), but the bias (1.36 +/- 3.10 ms/mmHg) was not significantly different from spectral analysis. No significant differences in BRS were found between beta-blocker users (n = 24) and non-users (n = 10) for either the processing method or source of ABP recording. Spectral analysis of cardiac BRS showed a better agreement between estimates obtained from the Finapres and aortic ABP.

Cardiovascular variability is/is not an index of autonomic control of circulation

To the Editor : As repeatedly underlined in this debate, neural cardiovascular (CV) regulation is characterized by a complex interaction between central and reflex mechanisms, with the contribution of other important factors such as respiratory frequency and depth. It would therefore be unrealistic

Reduced glomerular filtration rate in pre-dialysis non-diabetic chronic kidney disease patients is associated with impaired baroreceptor sensitivity and reduced vascular compliance

Small uncontrolled studies of dialysis-dependent CKD (chronic kidney disease) patients have demonstrated abnormalities of cardiovascular autonomic control and vascular compliance, which may contribute to adverse cardiovascular morbidity in this population. However, there is little information utilizing newer non-invasive techniques in pre-dialysis patients with increasing degrees of uraemia. In the present study, 55 non-dialysis-dependent non-diabetic CKD patients with mean GFR (glomerular filtration rate) of 27 ml x min(-1) x m(-2) were studied. All patients underwent a 10-min period of electrocardiographic and non-invasive blood pressure monitoring. Cardiac BRS (baroreceptor sensitivity) was calculated from the combined alpha-index. PWV (pulse wave velocity) measurement and determination of arterial wave reflexion by applanation tonometry was performed in all patients. Mean (S.D.) cardiac BRS was 10.8 (7.1) ms/mmHg and mean (S.D.) PWV was 8.6 (1.7) m/s. Reduced GFR was correlated with increased PWV and decreased cardiac BRS. On logistic regression analysis with adjustment for clinical significant risk factors, severely impaired renal function (assessed by GFR < 15 ml x min(-1) x m(-2)) was associated with increased large artery stiffness [odds ratio for PWV = 3.14 (95% confidence intervals, 1.03-9.53); P = 0.04] and increased cardiovascular autonomic dysfunction [odds ratio for BRS = 0.87 (95% confidence intervals, 0.75-1.80); P = 0.06]. In conclusion, non-dialysis dependent non-diabetic CKD patients with decreasing GFR have reduced cardiac BRS and increased large artery stiffness. This may have important prognostic and therapeutic consequences for the management of vascular disease in a pre-dialysis population.

Abnormalities in cardiac baroreceptor sensitivity in acute ischaemic stroke patients are related to aortic stiffness

Cardiac BRS (baroreceptor reflex sensitivity) is impaired following ischaemic stroke and predicts the risk of subsequent long-term death and disability. Impaired cardiac BRS may be due to impaired central processing of baroreceptor information following stroke or reduced baroreceptor activity due to increased large artery stiffness. We evaluated the relationship between large (aortic) artery stiffness and cardiac BRS during the acute phase of ischaemic stroke and in comparison with a group of stroke-free control subjects. Thirty-one ischaemic stroke patients were studied within 48 h of onset and again on day 14, along with 26 control subjects free of cerebrovascular disease. Cardiac BRS (determined by spectral analyses) and arterial stiffness estimated by PWVcf (carotid-femoral pulse wave velocity) using applanation tonometry were obtained. At baseline, cardiac BRS was lower in the stroke compared with the control group (4.3+/-2.3 compared with 6.5+/-4.2 ms/mmHg; P < 0.05). Cardiac BRS values were correlated with PWVcf at < 48 h (r = -0.51, P < 0.01) and on day 14 (r = -0.54, P < 0.01), but not in the control group (r = -0.27, P = not significant). In quantile regression models, taking into account the effect of all cardiovascular variables, cardiac BRS was independently related to PWVcf at baseline and on day 14 in the stroke patients, but stroke was not related to cardiac BRS level when other cardiovascular variables were considered. Wall stiffness of the arterial vessels involved in the baroreflex arc may account for, at least in part, the reduced cardiac BRS observed in acute stroke patients.

Bendrofluazide Fails to Reduce Elevated Blood Pressure Levels in the Immediate Post-Stroke Period

Introduction: Blood pressure (BP) levels, beat-to-beat blood pressure variability, dynamic cerebral autoregulation and cardiac baroreceptor sensitivity are frequently abnormal following acute stroke and are associated with an adverse short- and long-term prognosis. Thiazide diuretics are effective antihypertensive agents in preventing primary and secondary stroke, but their hypotensive and cerebral autoregulatory effects in the immediate post-stroke period have not been studied. Methods: Thirty-seven hypertensive neuroradiologically proven ischaemic stroke patients were randomized in a double-blind, placebo controlled, parallel group study to bendrofluazide 2.5 mg daily or matching placebo, within 96 h of stroke onset, for a 7-day period. Casual and non-invasive beat-to-beat arterial BP levels, cerebral blood flow velocity, ECG and transcutaneous carbon dioxide levels were measured within 70 ± 20 h of cerebral infarction and again 7 days later. Dynamic cerebral autoregulatory indices, pulse interval, BP variability and cardiac baroreceptor sensitivity were also calculated. Results: Small, non-significant falls were seen in casual and beat-to-beat BP levels over the 7-day period in both active and placebo-treated patients with no differences between treatments. No significant changes were seen in dynamic cerebral autoregulation or in cardiac baroreceptor sensitivity during the follow-up in either group. Conclusion: Following acute ischaemic stroke, the standard dose of bendrofluazide at 2.5 mg daily in this study sample did not lower systemic BP levels over the subsequent 7-day period. There was no evidence that bendrofluazide significantly altered cerebral autoregulation or improved cardiac baroreceptor sensitivity post-ictus. Bendrofluazide appears to be an ineffective hypotensive agent at the standard dosage in the initial post-stroke period.

Cardiac baroreceptor sensitivity: A prognostic marker in predialysis chronic kidney disease patients?

Small, uncontrolled studies of dialysis-dependent chronic kidney disease (CKD) patients have demonstrated abnormalities of cardiovascular autonomic control and vascular compliance, which may contribute to adverse cardiovascular morbidity in this population. However, there is little information utilizing newer, noninvasive techniques in predialysis patients with increasing degrees of uremia. One hundred and five nondialysis CKD patients with a median GFR of 23 mL/min/1.73 m(2) (range: 6 to 102) at baseline were studied. Cardiac baroreceptor sensitivity (BRS) was recorded by time- and frequency-domain techniques, and its relationship with increasing degrees of uremia studied. During a mean follow-up period of 42 months (range: 3 to 70), primary (death, dialysis, transplantation) and secondary (fatal and nonfatal cardiovascular events) outcome measures were recorded. The importance of cardiac BRS in comparison to other important renal and cardiovascular prognostic variables in predicting outcome was assessed. Median cardiac BRS by time domain analysis at baseline was 8.85 msec/mm Hg (interquartile range: 6.85), and impaired cardiac BRS was related to reduced GFR, increasing age, and hypertension on quantile regression analysis. 'Impaired' cardiac BRS was associated with a trend toward increased likelihood of both primary and secondary outcomes, and may act as a surrogate measure of other cardiovascular risk factors, including age, hyperlipidemia, hypertension, previous cardiovascular disease, and doubling of creatinine. Nondialysis-dependent CKD patients have impaired cardiac BRS, and this was related to decreasing GFR. There was a trend toward poorer prognosis in patients with impaired cardiac BRS that requires further study. Cardiac BRS may provide a simple, bedside, noninvasive assessment of overall cardiovascular risk in this population.

Losartan reduces muscle sympathetic nerve activity and increases cardiac baroreceptor sensitivity in patients with mild-to-medium hypertension,

Losartan reduces muscle sympathetic nerve activity and increases cardiac baroreceptor sensitivity in patients with mild-to-medium hypertension,