This study compared spontaneous baroreflex sensitivity (BRS) estimates obtained from an identical set of data by 11 European centers using different methods and procedures. Noninvasive blood pressure (BP) and ECG recordings were obtained in 21 subjects, including 2 subjects with established baroreflex failure. Twenty-one estimates of BRS were obtained by methods including the two main techniques of BRS estimates, i.e., the spectral analysis (11 procedures) and the sequence method (7 procedures) but also one trigonometric regressive spectral analysis method (TRS), one exogenous model with autoregressive input method (X-AR), and one Z method. With subjects in a supine position, BRS estimates obtained with calculations of alpha-coefficient or gain of the transfer function in both the low-frequency band or high-frequency band, TRS, and sequence methods gave strongly related results. Conversely, weighted gain, X-AR, and Z exhibited lower agreement with all the other techniques. In addition, the use of mean BP instead of systolic BP in the sequence method decreased the relationships with the other estimates. Some procedures were unable to provide results when BRS estimates were expected to be very low in data sets (in patients with established baroreflex failure). The failure to provide BRS values was due to setting of algorithmic parameters too strictly. The discrepancies between procedures show that the choice of parameters and data handling should be considered before BRS estimation. These data are available on the web site (http://www.cbi.polimi.it/glossary/eurobavar.html) to allow the comparison of new techniques with this set of results.

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The risk related to cardiovascular autonomic neuropathy dysautonomia should lead to a specific assessment of this complication of diabetes. The aim of this study was to estimate the accuracy of a battery of blood pressure (BP) and heart rate (HR) variability indexes obtained in different subgroups of diabetic subjects classified according to the conventional laboratory autonomic function tests (Ewing scores). Blood pressure was measured continuously at the finger level with a Finapres monitor while subjects were in the supine position and again while they were standing. Pulse intervals were derived from BP recordings and were taken as surrogates for R-R intervals. Subjects with borderline or definite cardiovascular autonomic neuropathy showed a similar degree of alterations of both HR and BP variability (spectral measures) and in the relationship between BP and HR (cross-spectral and sequence analysis). Subjects with no evidence of cardiovascular autonomic neuropathy on the basis of the conventional tests showed an altered relationship between BP and HR. This baroreceptor-HR reflex dysfunction could represent an early stage of cardiovascular autonomic neuropathy undetected by the conventional tests. The areas under the receiver operating characteristic plots indicated that the high-frequency peak of pulse interval was highly discriminant in the supine and standing positions. The cross-spectral analysis showed the best discrimination for the gain in the high-frequency range. For the sequence analysis, the slope was the best discriminant factor for any degree of cardiovascular autonomic neuropathy. In conclusion, these estimates of baroreceptor-HR function may provide a powerful tool for assessing cardiovascular autonomic neuropathy at any stage, including the early stage, which is not detected by the conventional tests.

Laude D, Baudrie V, Elghozi J-L. Applicability of recent methods used to estimate spontaneous baroreflex sensitivity to resting mice. Am J Physiol Regul Integr Comp Physiol 294: R142-R150, 2008. First published November 7, 2007 doi:10.1152/ajpregu.00319.2007.-Shortterm blood pressure (BP) variability is limited by the arterial baroreflex. Methods for measuring the spontaneous baroreflex sensitivity (BRS) aim to quantify the gain of the transfer function between BP and pulse interval (PI) or the slope of the linear relationship between parallel BP and PI changes. These frequency-domain (spectral) and time-domain (sequence) techniques were tested in conscious mice equipped with telemetric devices. The autonomic relevance of these indexes was evaluated using pharmacological blockades. The significant changes of the spectral bandwidths resulting from the autonomic blockades were used to identify the low-frequency (LF) and highfrequency (HF) zones of interest. The LF gain was 1.45 Ϯ 0.14 ms/mmHg, with a PI delay of 0.5 s. For the HF gain, the average values were 2.0 Ϯ 0.19 ms/mmHg, with a null phase. LF and HF bands were markedly affected by atropine. On the same 51.2-s segments used for cross-spectral analysis, an average number of 26.4 Ϯ 2.2 slopes were detected, and the average slope in resting mice was 4.4 Ϯ 0.5 ms/mmHg. Atropine significantly reduced the slopes of the sequence method. BRS measurements obtained using the sequence technique were highly correlated to the spectral estimates. This study demonstrates the applicability of the recent methods used to estimate spontaneous BRS in mice. There was a vagal predominance in the baroreflex control of heart rate in conscious mice in the present conditions. baroreceptors; heart rate; sympathetic; vagus nerve THE IMPORTANCE OF THE BAROREFLEX in blood pressure (BP) regulation in mice can be appreciated by the marked increase in BP variability that occurs after sinoaortic deafferentation of baroreceptors that are located in the carotid sinuses and aortic arch (9, 21). The ability of the baroreflex to buffer BP fluctuations varies depending on the frequency of the BP fluctuations (19). BP and heart rate (HR) fluctuate at regular frequencies, the magnitude of which can be accurately quantified using power spectral analysis (25, 30). The absolute frequency bands at which these oscillations occur in mice were analyzed in a previous report (3). One recent approach to estimating the spontaneous baroreflex sensitivity (BRS) over a stationary period is the calculation of the gain of the transfer function between BP and R-R interval in the low-frequency (LF) and high-frequency (HF) bands (20,28). This spectral analysis approach has been recently applied to conscious mice (2, 7, 9 -12, 16, 18, 32). Another recent approach is the dynamic evaluation of the spontaneous BRS called the sequence technique (4). This method is based on the computerized scanning of beat-to-beat series of systolic BP and R-R interval values in search of spontaneous sequences of consecutive increases o...

1 An investigation was made into the effects of conditioned running (1 h and 2h at 20mmin-'), which accelerates lipolysis, on the concentrations of tryptophan (Trp) in plasma, liver and brain and on 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in brain. 2 Running caused time-dependent increases in plasma free Trp and brain Trp of the rat, leading to increased brain 5-HT turnover as revealed by higher amounts of its metabolite, 5-HIAA. The ratio of brain Trp to plasma free Trp was decreased after 2 h of running. 3 Liver Trp content rose only after 3 h of running, while liver unesterified fatty acid (UFA) concentrations remained unmodified. 4 A comparison between food deprivation and running (both of which promote lipolysis) was performed. Running for 2 h affected to the same extent plasma Trp disposition when compared with 24 h food deprivation. Nevertheless, the ratio of brain Trp to plasma free Trp was decreased in the food-deprived rats, when compared to the runners. 5 Valine, an inhibitor ofentry ofTrp into the brain decreased its level there to the same extent in both controls and I h runners. 6 Nicotinic acid, which inhibits fat catabolism, completely abolished the plasma UFA increase induced by 1 h of running. The drug did not affect plasma free Trp, brain Trp, 5-HT or 5-HIAA but enhanced plasma total Trp level. 7 Naloxone, an opiate antagonist, which decreased running-induced lipolysis, did not alter plasma Trp disposition.8 Desipramine, an antidepressant compound, affected only peripheral Trp concentrations of the runners. Plasma free and total Trp concentrations were increased in desipramine-treated runners, compared with saline-treated runners. In addition, desipramine increased the ratio of brain Trp to plasma free Trp of the runners. Brain 5-HT and 5-HIAA were increased in both desipramine-treated controls and runners. 9 The results suggest that running, which like food deprivatiQn accelerates lipolysis, increases brain Trp content and then 5-HT turnover. Comparison of these two physiological situations suggests that effectiveness of brain Trp entry is much more altered by fasting.

The analysis of blood pressure (BP) and heart rate (HR) variability by spectral methods has proven a useful tool in many animal species for the assessment of the vagal and sympathetic contributions to oscillations of BP and HR. Continuous BP measurements obtained in mice by telemetry were used to characterize the spectral bandwidths of autonomic relevance by using an approach with no a priori. The paradigm was based on the autonomic blockades obtained with conventional drugs (atropine, prazosin, atenolol). The spectral changes were estimated in all of the combinations of spectral bandwidths. The effect of hydralazine was also tested using the same systematic analysis, to detect the zones of sympathetic activation resulting reflexly from the vasodilatory action of the drug. Two zones of interest in the study of the autonomic control of BP and HR were observed. The first zone covered the 0.15-0.60 Hz range of the systolic BP spectrum and corresponds to the low-frequency zone (or Mayer waves). This zone reflects sympathetic control since the power spectral density of this zone was significantly reduced with alpha1-adrenoceptor blockade (prazosin), while it was significantly amplified as a result of a reflex sympathetic activation (hydralazine). The second zone covered the 2.5-5.0 Hz range of the pulse interval spectrum and corresponded to the high-frequency zone (respiratory sinus arrhythmia) under vagal control (blocked by atropine). These zones are recommended for testing the autonomic control of circulation in mice.

The spectral analysis of SBP in the high frequencies shows that the changes in cardiac parameters are coupled with a decrease in sympathetic vasomotor control (-18%) and a reduction in diastolic pressure (-3.2%) in the response to the tilt test at the end of ITP. Spectral analysis could be a means of demonstrating impairment of autonomic balance for the purpose of detecting a state of fatigue that could result in overtraining.

To investigate the differences between heart rate (HR) variability and pulse rate (PR) variability, short-term variability of finger pulse wave and ECG signals were studied in 10 children with a fixed ventricular pacemaker rhythm (80 beats/min). Ten healthy children in sinus rhythm served as a reference population. Distal PR and HR were measured continuously using a Finapres device and an ECG respectively. Power spectra for HR and PR were calculated in both the supine and orthostatic positions. In paced subjects, PR spectra exhibited the characteristic respiratory peak, although the HR spectra were flat. Similarly, in healthy children the respiratory fluctuations were more pronounced when calculated from the finger pulse wave signal compared with the ECG signal. The overestimation of HR respiratory fluctuation resulting from distal PR measurement was more pronounced in the standing position; however, this postural effect was demonstrated only in healthy subjects. We observed mechanical respiratory modulation of distal PR independent of classical HR modulations. Our results suggest a mechanical respiratory influence via cardiac output and aortic transmural pressure changes on pulse wave velocity. We conclude that respiratory PR variability does not precisely reflect respiratory HR variability in standing healthy subjects and in patients with low HR variability. Consequently, HR modulation should be studied using the ECG signal rather than the distal pulse wave signal. However, when ECG recording is not available, the distal pulse wave is an acceptable alternative.