Variability in cardiovascular control: The baroreflex reconsidered

Although blood pressure control is often viewed as a paradigmatic example of a "homeostatic'' biological control system, blood pressure levels can fluctuate considerably over shorter and longer time scales. In modern signal analysis, coherence between heart rate and blood pressure variability is used to estimate baroreflex gain. However, the shorter the measurement period, the more variability this gain factor reveals. We review evidence that this variability is not due to the technique used for the estimation, but may be an intrinsic property of the circulatory control mechanisms. The baroreflex is reviewed from its evolutionary origin, starting in fishes as a reflex mechanism to protect the gills from excessively high pressures by slowing the heart via the ( parasympathetic) vagus nerve. Baroreflex inhibition of cardiovascular sympathetic nervous outflow is a later development; the maximally possible extent of sympathetic activity probably being set in the central nervous system by mechanisms other than blood pressure per se. In the sympathetic outflow tract not only baroreflex inhibition but also as yet unidentified, stochastic mechanisms decide to pass or not pass on the sympathetic activity to the periphery. In this short essay, the "noisiness'' of the baroreflex as nervous control system is stressed. This property is observed in all elements of the reflex, even at the-supposedly-most basic relation between afferent receptor nerve input and efferent-vagus-nerve output signa

Time-domain cross-correlation baroreflex sensitivity: performance on the EUROBAVAR data set

Objective To test a new method (cross-correlation baroreflex sensitivity, xBRS) for the computation of time-domain baroreflex sensitivity on spontaneous blood pressure and heart interval variability using the EUROBAVAR data set. Methods We applied xBRS to the 42 records in the EUROBAVAR data set, obtained from 21 patients in the lying and standing positions. One patient had a recent heart transplant and one was diabetic with evident cardiac autonomic neuropathy. xBRS computes the correlation between beat-to-beat systolic blood pressure and R - R interval, resampled at 1 Hz, in a sliding 10 s window, with delays of 0-5 s for interval. The delay with the greatest positive correlation is selected and, when significant at P = 0.01, slope and delay are recorded as one xBRS value. Each 1 s of the recording is the start of a new computation. Non-parametric tests are used. Results With patients in the lying position, xBRS yielded a value of 12.4 ms/mmHg compared with the EUROBAVAR sequential 16.2 ms/mmHg, and for the standing positions the respective values were 6.2 and 6.7 ms/mmHg, giving lying to standing ratios of 1.96 and 2.10, respectively. xBRS yielded results for all files, with 20 values per minute on average at a lower within-patient variance. Best delays were 0, 1 and 2 s, and the delay increased by 102 ms when the patient was in the standing position. The xBRS method was successful in the patients with diabetes and the heart transplant. Conclusion The xBRS method should be considered for experimental and clinical use, because it yielded values that correlated strongly with and were close to the EUROBAVAR averages, yielded more values per minute, had lower within-patient variance and measured baroreflex dela

Effect of clonidine on cardiac baroreflex delay in humans and rats

The delay τ between rising systolic blood pressure (SBP) and baroreflex bradycardia has been found to increase when vagal tone is low. The α(2)-agonist clonidine increases cardiac vagal tone, and this study tested how it affects τ. In eight conscious supine human volunteers clonidine (6 μg/kg po) reduced τ, assessed both by cross correlation baroreflex sensitivity and sequence methods (both P < 0.05). Experiments on urethane-anaesthetized rats reproduced the phenomenon and investigated the underlying mechanism. Heart rate (HR) responses to increasing SBP produced with an arterial balloon catheter showed reduced τ (P < 0.05) after clonidine (100 μg/kg iv). The central latency of the reflex was unaltered, however, as shown by the unchanged timing with which antidromically identified cardiac vagal motoneurons (CVM) responded to the arterial pulse. Testing the latency of the HR response to brief electrical stimuli to the right vagus showed that this was also unchanged by clonidine. Nevertheless, vagal stimuli delivered at a fixed time in the cardiac cycle (triggered from the ECG R-wave) slowed HR with a 1-beat delay in the baseline state but a 0-beat delay after clonidine (n = 5, P < 0.05). This was because clonidine lengthened the diastolic period, allowing the vagal volleys to arrive at the heart just in time to postpone the next beat. Calculations indicate that naturally generated CVM volleys in both humans and rats arrive around this critical time. Clonidine thus reduces τ not by changing central or efferent latencies but simply by slowing the hear

Time course analysis of baroreflex sensitivity during postural stress

Postural stress requires immediate autonomic nervous action to maintain blood pressure. We determined time-domain cardiac baroreflex sensitivity (BRS) and time delay (tau) between systolic blood pressure and interbeat interval variations during stepwise changes in the angle of vertical body axis (alpha). The assumption was that with increasing postural stress, BRS becomes attenuated, accompanied by a shift in tau toward higher values. In 10 healthy young volunteers, alpha included 20 degrees head-down tilt (-20 degrees), supine (0 degree), 30 and 70 degrees head-up tilt (30 degrees, 70 degrees), and free standing (90 degrees). Noninvasive blood pressures were analyzed over 6-min periods before and after each change in alpha. The BRS was determined by frequency-domain analysis and with xBRS, a cross-correlation time-domain method. On average, between 28 (-20 degrees) to 45 (90 degrees) xBRS estimates per minute became available. Following a change in alpha, xBRS reached a different mean level in the first minute in 78% of the cases and in 93% after 6 min. With increasing alpha, BRS decreased: BRS = -10.1.sin(alpha) + 18.7 (r(2) = 0.99) with tight correlation between xBRS and cross-spectral gain (r(2) approximately 0.97). Delay tau shifted toward higher values. In conclusion, in healthy subjects the sensitivity of the cardiac baroreflex obtained from time domain decreases linearly with sin(alpha), and the start of baroreflex adaptation to a physiological perturbation like postural stress occurs rapidly. The decreases of BRS and reduction of short tau may be the result of reduced vagal activity with increasing alph

Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated vasovagal response

OBJECTIVES - We set out to determine the effect of sublingual nitroglycerin (NTG), as used during routine tilt testing in patients with unexplained syncope, on hemodynamic characteristics and baroreflex control of heart rate (HR) and systemic vascular resistance (SVR). BACKGROUND Nitroglycerin is used in tilt testing to elicit a vasovagal response. It is known to induce venous dilation and enhance pooling. Also, NTG is lipophilic and readily passes cell membranes, and animal studies suggest a sympatho-inhibitory effect of NTG on circulatory control. METHODS Routine tilt testing was conducted in 39 patients with suspected vasovagal syncope (age 36 16 years, 18 females). Patients were otherwise healthy and free of medication. Before a loss of consciousness set in, oncoming syncope was cut short by tilt-back or counter-maneuvers. Finger arterial pressure was monitored continuously (Finapres). Left ventricular stroke volume (SV) was computed from the pressure pulsations (Modelflow). Spontaneous baroreflex control of HR was estimated in the time and frequency domains. RESULTS During tilt testing, 22 patients developed presyncope. After NTG administration but before presyncope, SV and cardiac output (CO) decreased (p <0.001), whereas SVR and HR increased (p <0.001) in all patients. Arterial pressure was initially maintained. Baroreflex sensitivity decreased after NTG. On Cox regression analysis, the occurrence of a vasovagal response was related to a drop in SV after NTG (hazard ratio 0.86, p = 0.005). CONCLUSIONS The cardiovascular response to NTG is similar in vasovagal and non-vasovagal patients, but more pronounced in those with tilt-positive results. The NTG-facilitated presyncope appears to be CO-mediated, and there is no evidence of NTG-induced sympathetic inhibition. (C) 2004 by the American College of Cardiology Foundatio

NUMMER 27 • VOORJAAR 2002

this article that one will be used. I have mentioned earlier that there are some weaknesses of the official construction, that makes it impossible to make an exact reproduction without measuring distances by hand. The problems are 1. the length of the horizontal bars is unknown 2. the shape of the surrounding &quot;circle&quot; is not clear. Only the height and the relative position of the horizontal bars is defined 3. the thickness of the &quot;circle&quot; is unknown 4. the thickness of the horizontal bars is unknown 5. and, not really a problem, the lables (x) on both angles are misleading and do not seem to fulfill a real purpose. Perhaps these points are unclear on purpose, so the font designer has some freedom to let the euro symbol fit nicely into a given font. Whatever the reason is, we have to make assumptions about the unclear parts, in order to be able to express the shape in terms of a program. I will, for the sake of clearness, assume that the surrounding shape is a circle. While it looks like it in the eu construction, it looks a bit more squeezed in the ecb one. In the official construction there is a variable x that seems to be some kind of a unit. The diameter of the circle is 11x if the horizontal bars and the circle have a width of 1

TNF signalling in tooth development

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Impact of age on the vasovagal response provoked by sublingual nitroglycerine in routine tilt testing

NTG (nitroglycerine) is used in routine tilt testing to elicit a vasovagal response. In the present study we hypothesized that with increasing age NTG triggers a more gradual BP (blood pressure) decline due to a diminished baroreflex-buffering capacity. The purpose of the present study was to examine the effect of NTG on baroreflex control of BP in patients with distinct age-related vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 years old, 17 females) with clinically suspected VVS (vasovagal syncope) and a positive tilt test. Mean FAP (finger arterial pressure) was monitored continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output) and SVR (systemic vascular resistance) were computed from the pressure pulsations (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In the first 3 min after NTG administration, BP was well-maintained in all patients. This implied an adequate arterial resistance response to compensate for steeper reductions in SV and CO with increasing age. HR (heart rate) increased and the BRS decreased after NTG administration. The rate of mean FAP fall leading to presyncope was; inversely related to age (r = 0.51, P = 0.005). Accordingly, patients with a mean FAP fall > 1.44 mmHg/s (median) were generally younger compared with patients with a slower mean FAP-fall (30 +/- 10 years compared with 51 +/- 17 years; P = 0.001). The main determinant of the rate of BP fall on approach of presyncope was the rate of fall in HR (r = 0.75, P <0.001). It was concluded that, in older patients, sublingual NTG provokes a more gradual BP decline compared with younger patients. This gradual decline cannot be ascribed to failure of the baroreflex-buffering capacity with increasing age. Age-related differences in the laboratory presentation of a vasovagal episode depend on the magnitude of the underlying bradycardic respons