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

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

Demographic and clinical data of all patients and of patients without and with hypertensive episodes.

a<p>With vs. without hypertension.</p>b<p>Mean (SD).</p>c<p>Left ventricular ejection fraction (LVEF)<40%.</p>d<p>Doxasozine or hydralazine.</p>e<p>Predialysis values.</p>*<p>Assessed in 103 patients, 52 with hypertensive episodes.</p>**<p>Assessed in 91 patients, 47 with hypertensive episodes.</p><p>ACE, angiotensin-converting enzyme; CRP, C-reactive protein; Hb, hemoglobin; LV, left ventricle; PTH, parathyroid hormone.</p

Representative tracings of continuous recordings of SBP and IBI oscillations and variability during intradialytic hypertension episodes with <i>decreased</i> (A) or <i>increased</i> heart rate (B).

<p>Tracings of a patient with marked intradialytic hypotension are depicted for comparison (C). The episodes associated with sudden changes in blood pressure are shown by the bolder parts of the tracings. LF, low frequency; HF, high frequency; IBI, interbeat interval.</p

Blood pressure variability, baroreflex sensitivity indices, interbeat intervals and low frequency/high frequency interbeat interval ratio at the beginning and at the end of hemodialysis^*.

*<p>Data given as median and interquartile range;</p>**<p>Number of patients: all sessions-108; without hypertension-51; with hypertension-57. Beginning-the initial 20 minutes of the dialysis session; End-the last 20 minutes of the dialysis session. Comparison of sessions without and with hypotension-Beginning:</p>a<p>p = 0.004;</p>b<p>p = 0.008; End:</p>c<p>p = 0.001;</p>d<p>p = 0.035.</p

Predictors of intradialytic hypertension based on logistic regression analysis.

<p>CI: confidence interval.</p><p>Variables in logistic regression models:</p><p>Clinical data: age, gender, dialysis vintage, history of intradialytic hypotension, history of hypertension, diabetes, ischemic heart disease, hyperlipidemia, anti- hypertensive medication, pre-dialysis SBP and IBI.</p><p>Laboratory data: pre-dialysis creatinine, calcium, phosphate, potassium, albumin, hemoglobin and PTH concentrations and CRP levels.</p><p>CDM measurements: pre-dialysis LF IBI, HF IBI, LF SBP, HF SBP, LF BRS and HF BRS.</p

Correlations of changes in interbeat intervals with changes in SBP during intradialytic hypertensive episodes associated with <i>increased</i> (n = 45) or <i>decreased</i> (n = 17) heart rate.

<p>HF, high frequency; LF, low frequency, IBI, interbeat interval.</p

SBP and interbeat interval and their variability indices before and during intradialytic hypertensive episodes associated with <i>increased</i> (n = 45) or <i>decreased</i> (n = 17) heart rate.

<p>Data are presented as box plots. The box stretches from the 25^th to the 75^th percentile; the median is shown as a small black square in the box. The range (the upper and the lower extreme values) is indicated by whiskers. HF, high frequency; LF, low frequency, IBI, interbeat interval.</p