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INTEGRATIVE |
1 Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba City, Ibaraki, 305-8574, Japan
2
Applied Physiology Laboratory, Toyota Technological Institute, Nagoya 468-8511, Japan
3
Faculty of Human Development, Kobe University, Kobe 657-8501, Japan
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Abstract |
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(Received 18 July 2006;
accepted after revision 15 August 2006;
first published online 17 August 2006)
Corresponding author T. Nishiyasu: Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba City, Ibaraki, 305-8574, Japan. Email: nisiyasu{at}taiiku.tsukuba.ac.jp
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Introduction |
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The ABR is known to influence the incidence and strength of MSNA bursts on a beat-to-beat basis and is thought to be the major modulator of MSNA in humans (Delius et al. 1972; Wallin et al. 1975; Sundlof & Wallin, 1978b; Wallin & Eckberg, 1982; Fagius et al. 1985; Macefield & Wallin, 1999; Kienbaum et al. 2001). Recent studies in both animals (Kamiya et al. 2005b) and humans (Ichinose et al. 2004b) suggest that orthostatic stress resets the ABR control over sympathetic nerve activity (SNA) to higher levels (upward resetting), which would augment the orthostatic activation of SNA and contribute to the prevention of postural hypotension (Kamiya et al. 2005b). Ichinose et al. (2004b) reported that application of a lower body negative pressure (LBNP) of –15 mmHg resets the ABR-mediated beat-to-beat control over total MSNA (overall MSNA control) to higher levels by upwardly resetting the ABR control over both the incidence and strength of MSNA bursts, while an LBNP of –35 mmHg resets ABR control over total MSNA still further upward by upwardly resetting control over burst strength without significantly altering control over burst incidence. These results indicate that the modulation of ABR control over MSNA in response to mild orthostatic stress differs from the response to moderate orthostatic stress. It is unknown, however, whether and how ABR control over the occurrence and strength of MSNA bursts is modulated during severe orthostatic stress that progressively increases to syncope. According to Ogoh et al. (2004), carotid baroreflex control over HR and mean arterial pressure (MAP) is largely absent during head-up tilt-induced syncope. Although several explanations for impairment of the baroreflex during development of syncope are conceivable (e.g. sympathoinhibition at orthostatic syncope and/or the baroreceptor stimulus is outside the functional range), the precise mechanism(s) remain unclear. That said, the results of the study by Ogoh et al. (2004) raise the possibility that the sensitivity of ABR control over beat-to-beat MSNA is impaired during development of orthostatic syncope; however, this has never been tested.
The purpose of the present study therefore was to test the hypothesis that, in humans, ABR-mediated beat-to-beat control over the occurrence and strength of MSNA bursts and overall MSNA is progressively modulated as orthostatic stress is increased until induction of syncope, and that ABR control over MSNA becomes impaired during development of orthostatic syncope.
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Methods |
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We studied 17 healthy volunteers (14 men and three women) with a mean age of 24 ± 1 year, mean body weight of 62.1 ± 2.5 kg and mean height of 168.9 ± 2.3 cm. The subjects were all non-smokers and none was taking any medication. The study, which was carried out in accordance with the Declaration of Helsinki, was approved by the Human Subjects Committee of the University of Tsukuba, and each subject gave informed written consent.
Procedures
After entering the test room, which was maintained at 25°C, each subject adopted a supine position with the lower torso, up to the iliac crest, enclosed in an LBNP box, which had a small door at the bottom that enabled recording of MSNA (using the microneurographic technique) from the tibial nerve at the popliteal fossa (Saito et al. 1990). Once we identified MSNA (see below for criteria), the door was closed and sealed. Then after a rest period of at least 15 min, the LBNP protocol and data collection were begun.
Raw recordings of arterial blood pressure and MSNA during supine rest (control) and at LBNPs of –50 mmHg and –60 mmHg for a subject who experienced symptoms of presyncope at LBNP = –60 mmHg are shown in Fig. 1. Control data were acquired for 5 min before application of LBNP. Then a series of 5 min steps was applied in which LBNP was progressively increased from –10 mmHg to –60 mmHg in 10 mmHg increments. The LBNP was terminated and the box pressure returned to the ambient pressure if the subject developed symptoms of presyncope, such as nausea, sweating, yawning, grey-out and dizziness, or if there was a reduction in systolic blood pressure to < 80 mmHg. Three subjects (all men) completed the LBNP protocol; nine (six men and three women) experienced LBNP-induced syncope, so that the LBNP protocol was terminated before completion (LBNP-induced syncope developed at –30 mmHg in one subject, at –40 mmHg in one subject, at –50 mmHg in three subjects and at –60 mmHg in four subjects). These nine subjects tolerated the final LBNP level for at least 2.5 min before development of presyncopal symptoms. For these syncopal subjects, calculation of basal data (HR, blood pressure and MSNA) and analysis of ABR control over MSNA for the final LBNP level were carried out using the data obtained during a 1–2 min period when blood pressure and MSNA were largely stable, before the symptoms of presyncope developed (Fig. 1). In five subjects who did not develop LBNP-induced syncope, the LBNP protocol was terminated before completion because the MSNA signal was no longer sufficiently clear for analysis (LBNP protocol was terminated at –50 mmHg for four subjects and at –60 mmHg for one subject). The data for these five subjects were therefore obtained until LBNP reached one level below the termination level.
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HR was monitored via a three-lead electrocardiogram (ECG). Beat-to-beat changes in blood pressure were monitored with finger photoplethysmography (Finapres 2300; Ohmeda, Englewood, CO, USA) using a cuff placed around the middle finger; the forearm and hand were supported so that the cuff was aligned at heart level. The subjects wore a mask connected to a respiratory flowmeter (RF-H; Minato Medical Science, Osaka, Japan), enabling measurement of respiratory flow and tidal volume. LBNP box pressure was measured using a pressure transducer. The analog signals representing the ECG, blood-pressure waveforms, respiratory flow, respiratory volume, box pressure, and the mean voltage neurogram (see below) were continuously recorded on an FM magnetic-tape data-recorder (MR-30; TEAC, Tokyo, Japan). The data were also digitized at a sampling frequency of 400 Hz through an analog-to-digital converter (Maclab/8e; ADInstruments, Castle Hill, Australia), then fed into a personal computer (Powerbook 1400C; Apple, Tokyo, Japan).
Multiunit muscle sympathetic nerve discharges were recorded using the microneurographic technique. A tungsten microelectrode with a shaft diameter of 0.1 mm and an impedance of 1–5 M
was inserted manually by an experimenter into the tibial nerve at the popliteal fossa and then adjusted until MSNA was encountered. The criteria for MSNA were spontaneous burst discharges that were synchronized with the heart beat and enhanced by Valsalva's manoeuvre or apnoea but unaffected by cutaneous touch or arousal stimuli (Delius et al. 1972; Vallbo et al. 1979; Saito et al. 1990). The experimenter did not touch the intraneural electrode once the protocol had begun. The neurogram was fed to a differential amplifier and amplified 100 000 times through a band-pass filter (500–3000 Hz), then full-wave rectified and integrated using a capacitance-integrated circuit with a time constant of 0.1 s. The mean voltage neurogram was continuously recorded as described above.
Data analysis
Beat-to-beat heart rate was calculated from the R-R intervals on the ECG. Beat-to-beat systolic and diastolic blood pressures (SAP and DAP, respectively) were obtained from the arterial-pressure waveform. MAP was calculated using the equation:
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| (1) |
Assessment of the ABR control over burst incidence, burst strength and total MSNA using spontaneous beat-to-beat fluctuations in both blood pressure and MSNA has been described in detail elsewhere (Ichinose et al. 2004b,c). Briefly, we investigated the ABR control over MSNA parameters during the control period and at each LBNP level as follows. First, taking into account the latency between the R wave of the ECG and the sympathetic burst (Fagius & Wallin, 1980), the DAP for each individual heart beat was related to the corresponding MSNA data. Because changes in MSNA correlate closely with the changes in DAP, but not with changes in SAP (Sundlof & Wallin, 1978b), we used DAP in this analysis. Second, all DAP values measured under each condition were grouped into 1 mmHg bins. In each group, diastoles were inspected to see whether or not they were associated with an MSNA burst, after which the percentage of diastoles associated with each MSNA burst (burst incidence/beat) were calculated. Third, we used signal-averaging to determine the burst strength and total MSNA activity for each diastolic-pressure bin (Halliwill, 2000). Briefly, the MSNA signals were averaged over a period corresponding to the length of the heart beat, taking into account the presumed latency from the R wave of the ECG, after which the area under the averaged MSNA signal was calculated. To calculate the burst strength related to each diastolic-pressure bin (burst strength/beat), only those MSNA signals associated with a burst were selected and averaged, enabling us to calculate the area of the averaged MSNA signal using the above-mentioned technique. The total MSNA related to each diastole-pressure bin (total activity/beat) was calculated as the area of the averaged MSNA signal created from all the MSNA signals in each bin, whether or not they were associated with an MSNA burst. Finally, the calculated burst incidence, burst strength and total MSNA obtained for each diastolic-pressure bin was plotted against the corresponding DAP, and linear regression analysis was performed for each diagram. At the high blood pressures tested, MSNA was often completely inhibited (i.e. burst incidence went to zero at the high DAPs). Within this range, MSNA did not change despite changes in DAP (i.e. burst incidence was always zero). Below this high DAP range, MSNA is negatively correlated with DAP, however. We therefore constructed the regression line relating DAP to MSNA using only DAPs and the corresponding MSNA data from levels below the high DAP range. We took the slope of each regression line as indicating the ABR sensitivity in the control over each variable. The points corresponding to the average DAP on the regression lines relating burst incidence or total MSNA to DAP were taken as the prevailing points for a given relationship and as an index of the MSNA corresponding to the ABR operating pressure. Because of the weak relationship between burst strength and DAP (described in detail in the Results and Discussion), we did not calculate the prevailing point for the regression line relating burst strength to DAP.
Statistical analysis
Data are presented as means ± S.E.M. For physiological responses (arterial blood pressure, HR and MSNA) and for the slope and prevailing point of the linear relationship relating MSNA and DAP, comparisons among control and each LBNP level were made using a one-way analysis of variance. To determine whether ABR control over MSNA was impaired during development of orthostatic syncope, in a syncopal subjects group, the slopes of the linear relationships between MSNA and DAP during the control period, at the LBNP level at which syncope occurred, and at the two preceding levels were, respectively, averaged and compared using one-way analysis of variance. Fisher's post hoc test was used to assess differences between group means. The characteristics of the ABR relationship between MSNA and DAP (DAP-burst incidence, DAP-burst strength and DAP-total MSNA) were determined using least-squares linear-regression analysis. Values of P < 0.05 were considered significant.
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Results |
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Table 1 shows the group values obtained for arterial blood pressure, HR, respiratory frequency, minute ventilation and MSNA during the control period and at each LBNP level. Application of LBNPs of –10 and –20 mmHg did not alter arterial blood pressure or HR. Sequential application of LBNPs ranging from –30 to –60 mmHg caused a progressive decline in SAP and pulse pressure (PP) and a progressive increase in HR. Respiratory frequency and minute ventilation were significantly increased at LBNPs of –40 and –30 mmHg, respectively, and both parameters increased further with continued increases in LBNP. The increases in LBNP also caused progressive increases in burst frequency, mean burst strength and total MSNA. Burst incidence increased progressively until LBNP = –30 mmHg and then stabilized, so that there were no further increases at LBNPs of –40 to –60 mmHg.
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Figure 2 shows the linear regression lines relating burst incidence, burst strength, and total MSNA to DAP for a non-syncopal subject (Fig. 2A, C and E) and for a syncopal subject who experienced syncope at LBNP = –60 mmHg (Fig. 2B, D and F). The derived variables describing ABR control over burst incidence, burst strength and total MSNA are presented for the group in Tables 2, 3 and 4, respectively. Figure 3 shows the group averaged values of the slopes of the linear regression lines relating burst incidence (Fig. 3A), burst strength (Fig. 3B) and total MSNA (Fig. 3C) to DAP in the syncopal and non-syncopal subjects during the control period and at the three highest LBNP levels are shown in Fig. 3. All of the subjects showed significant negative correlations between burst incidence or total MSNA and DAP under all conditions (Tables 2 and 4). Not all of the subjects showed a significant negative correlation between burst strength and DAP, however. The numbers of subjects who exhibited significant negative correlations between burst strength and DAP in the control period and at each LBNP level were 10, 6, 11, 12 (of 17), 11 (of 16), 7 (of 11) and 4 (of 7), respectively, and even in those who did show significant relationships, the correlation coefficients were smaller than those relating burst incidence or total MSNA to DAP (Table 3).
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Discussion |
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Although the cardiovascular responses to severe central hypovolaemia have been previously examined using high levels of LBNP in humans (Stevens & Lamb, 1965; Murray et al. 1968; Wolthuis et al. 1974; Cooke et al. 2004), data on sympathetic vasomotor activity under such conditions are quite limited. To the best of our knowledge, only two earlier studies reported MSNA data at LBNPs above –50 mmHg (Khan et al. 2002; Convertino et al. 2004). Khan et al. reported that at an LBNP of –60 mmHg burst frequency was increased by 340% from control in three subjects (before the bed rest condition in their study), while Convertino et al. reported a 262% increase in four subjects. In the present study, we found that, at the same LBNP, burst frequency was increased by 292 ± 35.2% from control in non-syncopal subjects (n = 3) and by 310 ± 24.5% from control in subjects who experienced syncope at –60 mmHg LBNP (n = 4). The average increase in burst frequency for all seven subjects was 302 ± 19.4% from control. Collectively then, the results of those earlier studies and our present study all indicate that an LBNP of –60 mmHg evokes about a 300% increase in burst frequency in healthy subjects. Furthermore, as far as we know this is the first study in which burst strength was quantified and total MSNA was calculated at such high LBNPs. This is advantageous because total MSNA is dependent on both burst frequency and burst strength and is thus a better index for quantifying the level of MSNA than is either of those variables separately (Victor & Leimbach, 1987; Hjemdahl et al. 1989; Vissing et al. 1989; Ichinose et al. 2004b,c). We also found that, for the same seven subjects, the average mean burst strength was increased by 191 ± 17.3% from control, while total MSNA was increased by 580 ± 73.8% from control at LBNP = –60 mmHg. The percentage increase in total MSNA was thus about twofold greater than the percentage increase in burst frequency (302 ± 19.4%). This suggests that activation of MSNA under conditions of central hypovolaemia sufficient to cause syncope is far greater than previously thought, and that under such conditions vasomotor sympathetic activity is increased nearly sixfold in healthy human subjects.
Sundlof & Wallin (1978b) quantified ABR control in humans in terms of both burst incidence and burst strength using the linear relationship between spontaneous variations in DAP and MSNA. They also found that burst incidence correlated closely with DAP during application of LBNP (–5 to –40 mmHg) (Sundlof & Wallin, 1978a), just as it did under control conditions. However, the progressive modulation of ABR control over burst incidence that occurred as orthostatic stress was increased to levels sufficient to induce syncope had never been demonstrated. Consistent with earlier studies (Sundlof & Wallin, 1978a; Ichinose et al. 2004b), we found that the close relationship between burst incidence and DAP was maintained from the control conditions across all LBNP levels (Table 2), suggesting that ABR control over burst incidence is maintained irrespective of the level of orthostatic stress. What is more, our results show that under orthostatic stress the upward resetting of ABR control over burst incidence has an upper limit that is reached at around –40 mmHg, and that the sensitivity of ABR control over burst incidence is diminished under severe orthostatic stress.
We found that burst frequency gradually increased with increasing LBNPs, which is in agreement with earlier reports (Sundlof & Wallin, 1978a; Victor & Leimbach, 1987; Vissing et al. 1989; Khan et al. 2002; Convertino et al. 2004; Ichinose et al. 2004b). Burke et al. (1977) described three patterns of increase in burst frequency that occur as a subject goes from a supine to a sitting position and then to a standing position. The increase in burst frequency was achieved via (1) increases in burst incidence, (2) increases in HR with a constant burst incidence, and (3) increases in both burst incidence and HR. This suggests an interaction between the mechanisms controlling HR and burst incidence in the regulation of burst frequency. Our results showed that at LBNPs of –10 and –20 mmHg, the increase in burst frequency was achieved through the upward resetting of ABR control over burst incidence without a significant change in HR. At LBNPs ranging from –40 to –60 mmHg, by contrast, increases in burst frequency beyond those seen at –30 mmHg were accomplished without further upward resetting, but with an increase in HR. This suggests that the mechanisms mediating ABR control over burst incidence and HR may interact to regulate burst frequency, and that the reflex increase in HR that occurs in response to severe orthostatic stress may work to increase MSNA as well as maintain cardiac output. The underlying mechanisms that govern the interrelation between the control over HR and the control over SNA remain uncertain, however.
We found several differences in the ABR control over burst strength and burst incidence during the LBNP protocol. The relatively weak relationship between burst strength and DAP, as compared to the close relationship between burst incidence and DAP, suggests that input from the arterial baroreceptors is not strong enough to exert the same degree of control over burst strength that it exerts over burst incidence. It is therefore likely that inputs other than those from the arterial baroreceptors exert stronger effects on burst strength. This notion is consistent with the findings of earlier studies in both animals (Malpas & Ninomiya, 1992a,b; Malpas et al. 1996) and humans (Hjemdahl et al. 1989; Sverrisdottir et al. 2000; Kienbaum et al. 2001; Ichinose et al. 2004b,c). In anaesthetized cats, for example, arterial chemoreflex stimulation is reported to primarily affect the amplitude of renal SNA rather than burst occurrence (Malpas & Ninomiya, 1992b). In humans, moreover, an increase in MSNA burst amplitude (without a change in the number of bursts) has been observed during mental stress (Hjemdahl et al. 1989). In the present study, we found that the weak relationship between burst strength and DAP was maintained throughout the LBNP protocol, suggesting that, in humans, mechanisms other than the ABR (e.g. cardiopulmonary baroreceptors) play key roles in modulating the burst strength elicited by orthostatic stress.
It has been suggested that the upward resetting of ABR control over SNA in response to orthostatic stress augments the activation of SNA, thereby contributing to the prevention of postural hypotension (Ichinose et al. 2004b; Kamiya et al. 2005b). Our results suggest that in humans MSNA is progressively increased in response to increasing orthostatic stress through the gradual upward resetting of ABR control over MSNA. Given that ABR control over total MSNA is dependent on its control over both burst incidence and strength (Ichinose et al. 2004b,c), the upward resetting of ABR control over total MSNA elicited by LBNPs up to –30 mmHg would reflect the upward resetting of ABR control over both burst incidence and strength. On the other hand, because there is no further upward resetting of ABR control of burst incidence at LBNPs higher than –30 mmHg, the upward resetting of ABR control over burst strength would be the major cause of the further upward resetting of ABR control over total MSNA seen at LBNPs above –30 mmHg. These results confirm our previous results (Ichinose et al. 2004b) and provide additional evidence that the mechanisms underlying the progressive upward resetting of ABR control over MSNA in response to increasing orthostatic stress are not uniform over the range of mild to very severe orthostatic stress.
We cannot provide a definitive explanation of the mechanism(s) responsible for the progressive modulation of ABR-mediated beat-to-beat control over MSNA in response to increasing orthostatic stress. It is possible this modulation reflects the interactions between ABR and other systems contributing to the regulation of SNA. For instance, it has been suggested that afferent neural information emanating from the cardiopulmonary baroreceptors influences the ABR at sites within the central nervous system (CNS) (Victor & Mark, 1985; Pawelczyk & Raven, 1989; Ogoh et al. 2003; Charkoudian et al. 2004, 2005; Ichinose et al. 2004a). Because the nucleus tractus solitarii (NTS) receives several visceral inputs, including afferents from arterial and cardiopulmonary baroreceptors, any interaction between those types of baroreflexes may well take place within the NTS (Spyer, 1990; Li et al. 1998; Potts et al. 2003). In particular, a progressive modulation of the ABR control over the incidence and strength of sympathetic bursts during gradual unloading of the cardiopulmonary baroreceptors, as was found in this study, could only be affected within such a site of integration.
Alternatively, the modulation of ABR control over MSNA might be associated with the unloading of the arterial baroreceptors themselves. For example, the upward shift of the DAP–MSNA relationship during LBNP could reflect increased MSNA due to unloading of the arterial baroreceptors induced by reductions in SAP and PP, even though the average DAP remained unchanged. Moreover, the DAP–MSNA relationship could approach the upper plateau of the sigmoidal baroreflex function through unloading of the arterial baroreceptors; if so, this could be one cause for the reduction in the slope of the DAP–burst incidence line at high levels of LBNP and the reduction in the slope of the DAP–MSNA (all three parameters) line prior to the orthostatic syncope. Earlier studies suggested that LBNP levels not sufficient to cause hypotension (less than –20 mmHg) selectively unload cardiopulmonary baroreceptors without changing afferent activity from arterial baroreceptors (Zoller et al. 1972; Johnson et al. 1974; Rowell, 1986). On the basis of those reports, the modulation of ABR control over MSNA under mild LBNP ought to be induced by unloading the cardiopulmonary baroreceptors without unloading arterial baroreceptors. However, it should be noted that according to Taylor et al. (1995), a small reduction in central blood volume induced by mild LBNP actually reduces the dimensions of the aortic baroreceptive areas. In light of this finding, the modulation of the beat-to-beat control over MSNA mediated by ABR during progressive increases in LBNP may be associated with unloading of both the cardiopulmonary and arterial baroreceptors. In any case, the precise mechanisms remain to be elucidated.
The function of the ABR during development of orthostatic syncope is largely unknown. Ogoh et al. (2004) reported that as presyncopal symptoms develop during head-up tilt in humans, the sensitivity of the carotid baroreflex control over HR and MAP declines substantially, and then declines still further during syncope. In addition, Kamiya et al. (2005a) recently reported that low frequency oscillations in MSNA are reduced though MSNA remains elevated during the early phase of development of head-up tilt-induced syncope. These results suggest that one or more control systems governing MSNA are modulated prior to the inhibition of MSNA during the development of orthostatic syncope. Our results confirm those earlier reports and show that the sensitivities of the ABR control over burst incidence, burst strength and total MSNA are all substantially diminished prior to the apparent inhibition of MSNA during the development of orthostatic syncope. We believe it is unlikely that this reflects a sudden reduction in the responsiveness of the arterial baroreceptors; more likely, the influence of the arterial baroreceptors on MSNA is inhibited within the CNS. It has been hypothesized that the withdrawal of sympathetic nerve activity and the concomitant bradycardia seen during orthostatic syncope (vasovagal reaction) is initiated from receptors situated in the inferior part of the left ventricle, which are activated by the combination of low cardiac filling secondary to venous pooling and an increased inotropic state of the heart (often termed the ‘Bezold-Jarisch reflex’) (Madsen & Secher, 1999; Kinsella & Tuckey, 2001; Campagna & Carter, 2003). We suggest that during development of orthostatic syncope, the cardiac depressor reflex may be activated and may initially act within the CNS to inhibit the effect of ABR on SNA. Subsequently, ABR function may be overridden completely, so that withdrawal of sympathetic activity and bradycardia occur concomitantly with the severe hypotension that leads to syncope. However, the precise mechanisms remain to be determined.
Limitations
To evaluate the ABR control over MSNA, we examined spontaneous fluctuations in blood pressure and MSNA. There are several limitations attached to this approach. Although the linear relationship between the spontaneous fluctuations in MSNA and DAP has been demonstrated previously (Sundlof & Wallin, 1978a,b; Kienbaum et al. 2001; Ichinose et al. 2004b,c), spontaneous blood pressure fluctuations are not particularly large. This means that the ABR stimulus response range that can be examined with this method is limited (within 20 mmHg). Although this is a narrower range than is obtained using other methods, such as the neck-chamber technique (Pawelczyk & Raven, 1989; Ogoh et al. 2003; Ichinose et al. 2004a) or invasive pharmacological manipulation (Halliwill et al. 1996), a 20 mmHg change in blood pressure is within the physiological range and should be a good reflection of the ABR control over MSNA under physiological conditions. Furthermore, to investigate the reflex effect elicited when two or more inputs are summed (e.g. the arterial and cardiopulmonary baroreceptor inputs in this study) it is important to use inputs that are small enough not to cause saturation of the output due to the inherent limitation on the effector responses of the system (Sagawa, 1983). On that basis, our experimental results can be taken as indicative of physiological modulation of the ABR control over MSNA during orthostatic stress.
In conclusion, our results show that in humans ABR controls over burst incidence, burst strength and total MSNA are all progressively modulated as orthostatic stress is increased until induction of syncope. Furthermore, the sensitivity of ABR control over the aforementioned MSNA variables was substantially reduced during the development of syncope. We suggest that progressive modulation of ABR function is one of the mechanisms mediating the gradual increase in MSNA as orthostatic stress increases, and that impairment of ABR control over sympathetic vasomotor activity leads to the severe hypotension associated with orthostatic syncope.
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P < 0.05 versus the 2nd LBNP level.