Heart rate response to blood pressure variations: sympathetic activation versus baroreflex response in patients with end-stage renal disease.

BACKGROUND: Continuous systolic blood pressure (SBP) and interbeat intervals (IBI) recordings reveal sequences of consecutive beats in which SBP and heart rate change in opposite direction, representing negative feedback baroreflex mechanisms, as well as sequences in which SBP and heart rate change in the same direction (non-baroreflex), believed to represent feedforward control mechanisms. The present study was undertaken to assess the relationship between baroreflex and non-baroreflex sequences in end stage renal insufficiency. METHODOLOGY/PRINCIPAL FINDINGS: Continuous beat-to-beat SBP and IBI monitoring was performed in patients on chronic hemodialysis (HD, n=72), in age-matched patients after renal transplantation (TX, n=41) and healthy (control) individuals (C, n=34). The proportion of baroreflex and nonbaroreflex episodes and the b coefficients (the regression line slope of SBP-IBI correlation) were determined using a newly developed 1 minute sliding window method, the classical sequence technique and the "Z" coefficient method. Analysis using the 1 minute sliding window showed an increased proportion of baroreflex episodes in controls and HD, and predominance of nonbaroreflex episodes in TX. An increased proportion of nonbaroreflex episodes in TX patients relative to HD was also revealed by the "Z" method. Baroreflex and nonbaroreflex b coefficients obtained by all methods were markedly decreased in HD. This alteration was reversed at least partly in TX. In HD, both baroreflex and nonbaroreflex b coefficients were inversely correlated to age and CRP levels; in TX, the nonbaroreflex b coefficient was influenced by the type of calcineurin inhibitor. CONCLUSION/SIGNIFICANCE: Renal status affects the contribution of baroreflex and nonbaroreflex mechanisms and the strength of SBP-IBI relationship. The predominant contribution of nonbaroreflex mechanisms in TX may be suggestive of enhanced central sympathetic control. Our data may be relevant for understanding of the pathogenesis and selection of appropriate treatment of post-transplant hypertension.

Sympathetic nervous system function and dysfunction in chronic hemodialysis patients.

Adequate sympathetic nervous system activation is essential for the compensatory mechanisms of blood pressure maintenance during the hemodialysis (HD) procedure. Chronic sympathetic nervous system overactivity, however, may lead to the development of hypertension and cardiovascular disease in HD patients. The present review focuses on recent findings on the sympathetic nervous system activity in these patients. Sympathetic overactivity has been demonstrated directly by muscle sympathetic nerve activity recordings (MSNA) in chronic renal disease, but only rarely in HD patients. In the latter, sympathetic activity has mostly been assessed using indirect methodology. Decreased heart rate variability, increased blood pressure variability (BPV), and suppressed baroreflex function are believed to represent chronic sympathetic overactivity in HD patients. The HD procedure and ultrafiltration are associated with enhanced sympathetic activity and baroreflex activation. During most episodes of intradialytic hypotension, the baroreflex is adequately activated; sympathetic withdrawal with bradycardia, however, has been reported during excessive hypovolemia. Sympathetic overactivity is also believed to be a mechanism associated with intradialytic hypertensive episodes and refractory hypertension. While successful renal transplantation is associated with improvement of heart rate variability (HRV), improvement and restoration of baroreflex function, persistent sympathetic overactivity has been documented in transplanted patients using MSNA recordings. Decreased HRV and baroreflex function have been reported to be associated with increased mortality and morbidity in HD patients. The predictive value of sympathetic outflow assessed by MSNA has yet to be determined. Optimization of HD treatment, pharmacological interventions, and renal sympathetic denervation are several approaches targeting sympathetic overactivity to improve cardiovascular morbidity and mortality.

Brain activation and heart rate during script-driven traumatic imagery in PTSD: preliminary findings.

Patients with posttraumatic stress disorder (PTSD) experience psychological and physiological distress. However, imaging research has mostly focused on the psychological aspects of the disorder. Considered an expression of distress, heart rate (HR) in PTSD is often elevated. In the current study, we sought to identify brain regions associated with increased HR in PTSD. Nine patients with PTSD and six healthy trauma survivors were scanned while resting, clenching teeth, and listening to neutral and traumatic scripts. Brain function was evaluated using H2O15 positron emission tomography (PET). HR was monitored by electrocardiogram. Data were analyzed using statistical parametric mapping (SPM). Subjects with PTSD exhibited a significant increase in HR upon exposure to traumatic scripts, while trauma survivors did not. Correlations between regional cerebral blood flow and HR were found only in patients with PTSD, in orbitofrontal, precentral and occipital regions. Neither group showed correlation between rCBF and HR in the amygdala or hippocampus. These preliminary results indicate that "top down" central nervous system regulation of autonomic stress response in PTSD may involve associative, sensory and motor areas in addition to regions commonly implicated in fear conditioning.

Sympathetic activation and baroreflex function during intradialytic hypertensive episodes.

BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI) and systolic blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF) and high (HF) frequency ranges were assessed using the complex demodulation technique (CDM). Intradialytic hypertensive episodes were associated with an increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of-dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes are associated with higher end-of-dialysis blood pressure, suggesting that intradialytic hypertension may play a role in generation of interdialytic hypertension.

Delayed effect of blood pressure fluctuations on heart rate in patients with end-stage kidney disease.

The time delay of the baroreflex may be affected by decreased autonomic activity in uremia. To assess the magnitude and the time delay of heart rate response in patients with end-stage renal disease, continuous beat-to-beat intervals (IBI) and systolic blood pressure (SBP) recordings were monitored in hemodialysis (HD) patients (n = 72), in patients after renal transplantation (TX) (n = 41) and in age-matched controls (C) (n = 34). A 2-term prediction model was computed, in which each IBI change was represented as a function of SBP difference values of two immediately preceding beats. Baroreflex slope and the frequency domain variables low frequency (LF) α index, phase shift, and lag time were also calculated. b1 coefficient, representing the dependence of IBI difference with the first previous SBP difference was lower in HD than in Cs, but increased after TX. b1 correlated with age, baroreflex slope, and LF α, and b2 (the 2nd term), with both the phase shift between SBP and IBI and lag time. The latter was lower in Cs than in HD or transplanted patients. These findings show that the time delay of the heart rate response to SBP variations is increased in renal insufficiency. The prolonged delay may contribute to the circulatory instability in uremic patients.

Baroreflex sensitivity and sympatho-vagal balance during intradialytic hypotensive episodes.

OBJECTIVES: The role of the baroreflex function in the pathogenesis of hemodialysis-associated hypotension is controversial. Complex demodulation technique (CDM), providing continuous assessment of the amplitude of cardiovascular oscillation over time, is particularly suitable to assess dynamic changes in autonomic nervous system and baroreceptor sensitivity (BRS) during dialysis. In the present study, CDM was used to determine the effects of dialysis treatment on BRS and to characterize BRS changes during acute intradialytic hypotension. METHODS: Continuous beat-to-beat blood pressure and interbeat intervals (IBIs) were monitored in 93 chronic patients without (n = 70) and with (n = 26) hypotension during 96 dialysis sessions. The amplitudes of SBP and DBP, IBIs, and BRS change in the low-frequency (around center frequency of 0.09 Hz) and high-frequency (around center frequency of 0.30 Hz) ranges were followed during the whole dialysis session. RESULTS: Hemodialysis treatment was associated with increased low-frequency BRS, especially in sessions without hypotension. Hypotensive episodes were associated with significant increases in both low-frequency BRS and high-frequency BRS, mainly in patients with severe hypotension. The magnitude of the increase in baroreflex indices was proportional to the decrease in blood pressure. Low-frequency IBI/high-frequency IBI ratio, a marker of sympatho-vagal balance, did not significantly change during hypotension. CONCLUSION: Our study shows that the baroreflex mechanism is preserved and adequately activated during intradialytic hypotension. Other factors, such as ischemic heart disease, left ventricular dysfunction, and inadequate arteriolar tone, rather than failure of baroreflex function, are more likely to be responsible for dialysis-induced hypotension.

Restoration of baroreflex function in patients with end-stage renal disease after renal transplantation.

BACKGROUND: Renal transplantation improves the uraemic autonomic dysfunction and heart rate variability (HRV). The effects of successful transplantation on blood pressure variability (BPV) and baroreflex function are not well defined. METHODS: BPV, HRV and baroreceptor indices were determined in (1) 52 non-diabetic chronic haemodialysis patients, (2) 44 transplanted patients, 24 in the first year after renal transplantation (< or =1 year) and 20 at least 1 year (>1 year) after renal transplantation, and (3) 41 control individuals with normal renal function, age-matched to (1) and (2). Power spectrum analysis of interbeat intervals (IBI) and systolic blood pressure (SBP) was performed in the low-frequency (LF 0.04-0.15 Hz) and the high-frequency (HF 0.15-0.40 Hz) bands. Spontaneous baroreceptor sensitivity (BRS) was determined by the sequence (slope) and spectral (alpha coefficient) techniques. RESULTS: In haemodialysis patients, BPV was increased, while HRV, BRS slope and LF alpha and HF alpha coefficients were markedly decreased as compared to control individuals. Renal transplantation was associated with normalization of BPV at short term (< or =1 year) and long term and with improvement of HRV at a long-term (>1 year) follow-up. In patients with long-standing functioning grafts (>1 year), baroreceptor indices were significantly increased and returned to values similar to those of the control subjects. CONCLUSIONS: Our data show that renal transplantation improves blood pressure and HRV and restores baroreflex function to near normal range on the long-term follow-up. These effects may contribute to the improvement of blood pressure control and survival after successful transplantation.

Blood pressure and heart rate variability in patients on conventional or sodium-profiling hemodialysis.

BACKGROUND: Autonomic nervous system dysfunction and dialysate sodium (Na) concentration are believed to play a role in the pathogenesis of hemodialysis-related hypertension. The present study was undertaken to determine whether increases in blood pressure in hemodialysis patients are associated with changes in heart rate variability (HRV), a measure of the autonomic nervous system function, and long-term exposure to increased dialysate Na concentration. METHODS: Baseline clinical, biochemical data and HRV of patients undergoing increased Na profiling dialysis (High-Na, n = 9) and on conventional treatment (Control, n = 11) were compared with those obtained after one year of study. RESULTS: After one year, the mean predialysis systolic blood pressure (SBP) increased in seven patients of the High-Na and in five of the Control group, and decreased or remained unchanged in the remaining subjects. Initial HRV was significantly higher in patients with increased SBP, and it increased further in these patients after one year. At the end of the study, post-dialysis plasma Na, osmolality, and weight gains were significantly higher in the High-Na group. No significant correlation, however, was found between individual changes in intradialytic sodium elimination and the alterations in blood pressure. CONCLUSION: These data suggest that the dialysate sodium concentration, a most important determinant of interdialytic weight gain and fluid balance, is only partly correlated with long-term changes in blood pressure. An increased blood pressure over time may develop in a subset of hemodialysis patients with higher HRV, suggestive of increased sympathetic activity.

Predictors of haemodynamic instability and heart rate variability during haemodialysis.

BACKGROUND: The pathogenesis of haemodialysis-induced hypotension is multifactorial and may include autonomic nervous system dysfunction. The present study was undertaken to (i) determine heart rate variability (HRV) in chronic haemodialysis patients without and with haemodynamic instability (hypotension-prone) during ultrafiltration and (ii) identify patients at risk and the predictors of dialysis-related hypotension. METHODS: HRV was evaluated in 56 chronic haemodialysis patients without (stable; n = 27) and with symptomatic hypotension episodes (unstable; n = 29) during daytime, haemodialysis and night-time periods. Logistic regression analysis was performed in a model that included clinical and biochemical data and HRV measurements. RESULTS: HRV was significantly reduced in haemodynamically unstable as compared with the stable patients. LF/HF ratio, an index representative of sympathovagal balance, was significantly lower in unstable patients, especially in those with ischaemic heart disease and diabetes mellitus. In a logistic regression model including clinical data and HRV measurements, ischaemic heart disease and left ventricular systolic dysfunction were found to be the main predictors of haemodynamic instability. CONCLUSIONS: These data suggest that haemodynamic instability is strongly associated with a decreased HRV and an impaired sympathovagal balance, suggesting disturbed autonomic control in uraemic patients with cardiac damage. Patients with ischaemic heart disease, reduced left ventricular systolic function and decreased HRV may be at the highest risk to be haemodynamically unstable during haemodialysis. The role of early detection and treatment of ischaemic heart disease in preventing symptomatic hypotensive episodes in these patients remains to be determined.

Scaling vs. nonscaling methods of assessing autonomic tone in streptozotocin-induced diabetic rats.

We studied heart rate variability in rats by power scaling spectral analysis (PSSA), autoregressive modeling (AR), and detrended fluctuation analysis (DFA), assessed stability by coefficient of variation between consecutive 6-h epochs, and then compared cross-correlation among techniques. These same parameters were checked from baseline conditions through acute and chronic disease states (streptozotocin-induced diabetes) followed by therapeutic intervention (insulin). Cross-correlation between methods over the entire time period was r = 0.94 (DFA and PSSA), r = 0.81 (DFA and AR), and r = 0.77 (AR and PSSA). Under baseline conditions the scaling parameter measured by DFA and PSSA and the high-frequency (HF) component measured by AR fluctuated around an average value, but these fluctuations were different for the three methods. After diabetes induction, a strong correlation was found between the HF power and the short-term scaling parameter. Despite their differences in methodology, DFA and PSSA assess changes in parasympathetic tone as detected by autoregressive modeling.