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Author's present address P. J. Fadel: Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390–8586, USA.
We sought to quantify the contribution of cardiac output (Q) and total vascular conductance (TVC) to carotid baroreflex-mediated changes in mean arterial pressure (MAP) in the upright seated and supine positions. Acute changes in carotid sinus transmural pressure were evoked using brief 5 s pulses of neck pressure and neck suction (NP/NS) via a simplified paired neck chamber that was developed to enable beat-to-beat measurements of stroke volume using pulse-doppler ultrasound. Percentage contributions of Q and TVC were achieved by calculating the predicted change in MAP during carotid baroreflex stimulation if only the individual changes in Q or TVC occurred and all other parameters remained at control values. All NP and NS stimuli from +40 to −80 Torr (+5.33 to −10.67 kPa) induced significant changes in Q and TVC in both the upright seated and supine positions (P < 0.001). Cardiopulmonary baroreceptor loading with the supine position appeared to cause a greater reliance on carotid baroreflex-mediated changes in Q. Nevertheless, in both the seated and supine positions the changes in MAP were primarily mediated by alterations in TVC (percentage contribution of TVC at the time-of-peak MAP, seated 95 ± 13, supine 76 ± 17 %). These data indicate that alterations in vasomotor activity are the primary means by which the carotid baroreflex regulates blood pressure during acute changes in carotid sinus transmural pressure.
A number of investigations have utilized the application of brief periods of neck pressure (NP)/neck suction (NS) to evaluate carotid baroreceptor function at rest and during exercise (Potts et al. 1993; Potts & Raven, 1995; Norton et al. 1999b; Fadel et al. 2001). The advantage of rapid changes in NP/NS is that they mimic the physiological changes in carotid sinus pressure that would ordinarily occur in this region (Eckberg et al. 1975). In the development of this technique it has been well established that NP and NS stimuli decrease and increase carotid sinus transmural pressure, respectively, and elicit the expected carotid baroreflex-mediated responses in heart rate (HR) and mean arterial pressure (MAP) (Potts et al. 1993; Norton et al. 1999a). Although the alterations in blood pressure induced by NP and NS can indirectly affect aortic and cardiopulmonary baroreceptors, the brevity of this technique appears to obviate any counter responses emanating from extracarotid baroreceptors (Eckberg, 1980; Potts et al. 1993; Potts & Raven, 1995).
Changes in arterial blood pressure (ABP) due to alterations in carotid sinus transmural pressure with NP/NS have been used to assess carotid-vasomotor responses (Potts et al. 1993; Norton et al. 1999a). These findings were based upon the suggestion that the carotid baroreflex-induced changes in ABP were a function of changes in vascular smooth muscle tone brought about by reflex alterations in sympathetic nerve activity (SNA). This approach appeared justified for several reasons. (i) The peak HR response to NP/NS occurred within the first 2–3 s and returned to baseline at the time the peak blood pressure response occurred (Raven et al. 1997). (ii) Acute changes in carotid sinus transmural pressure appeared to have minimal effects on changes in stroke volume (Levine et al. 1990). (iii) Changes in NP/NS caused rather abrupt, although transient, changes in muscle SNA (Wallin & Eckberg, 1982; Rea & Eckberg, 1987; Fritsch et al. 1991). While these observations appear valid, there remains some question as to the specific interpretation of these data. For example, although peak HR changes occurred early in the stimulus, whether or not the peak blood pressure response was a temporal effect of changes in cardiac output, induced by alterations in HR, remains unclear. In addition, there is currently only one study that has evaluated stroke volume (SV) changes during carotid baroreflex stimulation and this investigation only used brief (500 ms) R wave-triggered changes in NP/NS from +40 to −65 Torr (+5.33 to −10.67 kPa; Levine et al. 1990). Hence, changes in SV may be quite different with the application of 5 s periods of NP/NS. Also, the investigations evaluating the muscle SNA responses to NP/NS were performed at rest in the supine position and there was no documentation of the concomitant changes in ABP induced by the NP/NS (Wallin & Eckberg, 1982; Rea & Eckberg, 1987). Therefore, interpretation of the results only applied to the resting supine position and were not applicable to other postures. Furthermore, it was not clear whether the reflex changes in muscle SNA actually induced alterations in ABP.
Recently, we have clearly identified that the changes in ABP induced by NP and NS are directly related to reflex-mediated changes in muscle SNA during seated rest (Fadel et al. 2001). However, the contribution of the reflex-mediated change in cardiac output to the changes in ABP remains a question because of the lack of quantification of SV during the application of NP/NS. The acquisition of beat-to-beat SV changes during NP/NS has been confounded by mechanical artifacts generated by the neck collar surrounding the pulse-doppler probe and the transferred movement of the probe placed at the suprasternal notch by the NP/NS protocol. Therefore, in the present investigation we utilized a simplified paired neck chamber that enables the acquisition of pulse-doppler recordings of ascending aortic blood flow velocity during NP/NS without mechanical interference from the collar (Raine & Cable, 1999). Since the paired neck chamber only distributes pressure to a small site of the neck overlying the carotid sinus baroreceptors, we first sought to validate the carotid baroreflex-mediated changes in HR and MAP elicited by the paired neck chamber by comparing these responses to those obtained with a traditional neck chamber, which covers the anterior two-thirds of the neck.
Our primary goal was to determine the involvement of reflex changes in cardiac output (Q) to NP/NS-induced changes in ABP and thereby proportion the NP/NS changes in ABP between Q and total vascular conductance (TVC) reflex responses. In addition, we examined the influence of cardiopulmonary baroreceptor unloading and loading on the carotid baroreflex-mediated changes in Q and TVC by performing measurements in the seated upright and supine positions. The reason for using the upright position was to evaluate if the proportionality of Q and TVC would be different because of the unloaded cardiopulmonary and arterial baroreceptors, which would result in a higher sympathetic neural activity as a background for the carotid baroreceptors to respond. On the contrary, the supine posture was used to assess if a maximized cardiac filling volume would cause a more effective cardiac response compared to the upright position. We hypothesized that: (i) reflex-mediated changes in TVC would be the primary means by which the carotid baroreflex alters ABP; and (ii) loading of the cardiopulmonary baroreceptors with a supine posture to decrease muscle SNA would decrease the contribution of changes in TVC to the reflex-mediated changes in ABP.
Seven men and five women (means ±s.e.m.: age, 27.2 ± 1.2 years; height 171.9 ± 2.2 cm; weight, 72.0 ± 5.2 kg) were recruited for voluntary participation in the present study. All subjects were free of known cardiovascular and pulmonary disorders, were normotensive non-smokers and were not taking prescribed or over the counter medications. Informed, written consent was obtained from all subjects, and the study protocol was approved by the University of North Texas Health Science Center Institutional Review Board for the use of human subjects. On experimental days, subjects were asked to abstain from caffeinated beverages for a minimum of 12 h and from strenuous physical activity for 24 h prior to arriving at the laboratory.
A simplified, paired neck chamber was devised by an adaptation of the neck chamber developed by Raine & Cable (1999). These chambers were adapted from gun ear protectors (Silencio Inc., Sparks, NV, USA). This new device was ideal for positioning over the carotid sinuses and came already cushioned with airtight sponge rubber surrounding the edges of the protectors to form a dependable seal against the contours of the anterior lateral neck. Therefore, the paired neck chamber allowed for easy access to the suprasternal notch for the measurement of the ascending aortic blood flow velocity during the application of NP and NS. We also utilized our traditional neck chamber (Pawelczyk & Raven, 1989; Potts et al. 1993) for comparisons of carotid baroreflex-mediated HR and MAP responses.
Cardiovascular variables were monitored beat to beat and recorded on a personal computer equipped with customized software. Heart rate was monitored utilizing a standard lead II electrocardiogram (ECG). The ECG signal output was connected to an ECG monitor (Hewlett-Packard 78342A, Andover, MA, USA) interfaced with the personal computer. ABP was measured non-invasively on a continuous basis using finger photoplethysmography (Finapres, Ohmeda, Madison, WI, USA). The Finapres was placed on the middle finger of the right hand and was supported on a modified surgical stand adjusted to position the finger cuff at heart level. Diastolic blood pressure recordings of the Finapres were matched with diastolic blood pressure obtained by brachial auscultation before recordings were started. Stroke volume was estimated from beat-to-beat measurements of ascending aortic pulse velocity waves obtained during continuous doppler recordings (RT6800, GE Medical Systems, Milwaukee, WI, USA). Stroke distance was calculated from the velocity time integral (VTI) of this signal. Aortic root diameter was determined using two-dimensional echocardiogram imaging from M mode recordings with the subject in the supine or left lateral recumbent position and SV calculated as: SV =π(D/2)2 VTI. Cardiac output (Q) was calculated from the product of SV and HR. Total vascular conductance (TVC) was calculated on a beat-to-beat basis from the ratio of Q to MAP (TVC =Q/MAP). In addition, total arterial compliance (TAC) was calculated on a beat-to-beat basis from the ratio of SV to pulse pressure (TAC = SV/pulse pressure).
Prior to any experimental testing each subject visited the laboratory for familiarization with the techniques and procedures of the experimental protocol. Two experimental sessions were conducted on separate days. On the first day, all testing was performed with the subject in an upright seated position, while on the second day subjects were studied in the supine position. Experimental procedures were performed at the same time of day. Since we had recently identified that the anatomic location of the carotid sinus bifurcation varied between subjects (Querry et al. 2001), the carotid sinuses of each subject were anatomically located non-invasively by using pulse-doppler ultrasound to ensure correct placement of the neck collars. After being instrumented for the measurement of HR and MAP, subjects were fitted with the traditional neck chamber that encircled the anterior two-thirds of the subject's neck for the application of NP and NS. Carotid baroreflex responsiveness was then assessed at rest using a random order of neck pressure presentation of +40, +20, 0, −20, −40, −60 and −80 Torr. Each amount of NP and NS was delivered to the carotid sinus for a period of 5 s during a 10–15 s breath hold at end-expiration. The breath hold minimized the effect of respiratory related modulation of HR and MAP (Eckberg, 1976). Three to four NP/NS were performed at each of the six pressures. The peak HR and MAP responses to each stimulus were determined and averaged to provide a mean response for each subject. Estimated changes in carotid sinus pressure were calculated as MAP minus the neck chamber pressure.
After the experiments with the traditional neck chamber each subject was fitted with the paired neck chamber at the site of the carotid sinuses. The same protocol used with the traditional neck chamber was performed with the simplified paired neck chamber to allow for the measurement of aortic blood flow velocity and thus, SV. The doppler probe was placed at the subject's suprasternal notch and beat-to-beat SV responses to each NP/NS stimulus were recorded throughout the breath-hold period and recorded on-line. Stroke volume responses to each stimulus were measured as the mean SV value obtained from all heartbeats during each 5 s period of NP and NS. The SV responses for each level of NP and NS were averaged to provide a mean response for each subject. On the second experimental day, the experimental trials using the traditional neck chamber and paired neck chamber were conducted in a counterbalanced order from day one to avoid any effects of order on the physiological responses to NP and NS.
The carotid-HR and the carotid-MAP responses were evaluated by plotting the peak changes in HR and MAP against estimated carotid sinus pressure (ECSP), respectively. Each carotid baroreflex stimulus-response curve was fitted to the logistic model described by Kent et al. (1972). This function incorporates the following equation:
where HR or MAP is the dependent variable, ECSP is the estimated carotid sinus pressure, A1 is the range of response of the dependent variable (maximum − minimum), A2 is the gain coefficient (i.e. slope), A3 is the carotid sinus pressure required to elicit equal pressor and depressor responses (centring point), and A4 is the minimum response of HR or MAP. Data were fitted to this model by non-linear least-squares regression (utilizing a Marquardt-Levenberg algorithm), which minimized the sum-ofsquares error term to predict a curve of ‘best fit’ for each set of raw data. The coefficient of variation for the overall fit of this model to the individual responses was found to be 18 % (Potts et al. 1993). The gain was calculated from the first derivative of the logistic function and the maximal gain (Gmax) was applied as the index of carotid baroreflex responsiveness. Threshold (CSPthr), the point where no further increase in the dependent variable occurred despite reductions in ECSP and saturation (CSPsat), the point where no further decrease in the dependent variable occurred despite increases in ECSP, were calculated as the maximum and minimum second derivatives, respectively, of the logistic function curve. For calculation of CSPthr and CSPsat, we applied equations described by Chen & Chang (1991) : CSPthr=−2.0/A2+A3 and CSPsat= 2.0/A2+A3. These calculations of CSPthr and CSPsat have been found to be the carotid sinus pressure at which MAP or HR is within 5 % of their maximal or minimal responses.
Since TVC is the sum of all regional vascular conductances, the percentage contributions of Q and TVC to carotid baroreflex-mediated changes in MAP can be calculated. This was achieved by calculating the predicted change in MAP during carotid baroreflex stimulation if only the individual changes in Q or TVC occurred and all other parameters remained at control levels (Augustyniak et al. 2000; Collins et al. 2001). The percentage contributions of Q and TVC were calculated as follows:
where MAPQ is the MAP response to carotid baroreceptor stimulation due to Q alone, MAPTVC is the MAP response to carotid baroreceptor stimulation due to TVC alone, MAPcontrol is the MAP value prior to NP/NS, Qcontrol is the Q value prior to NP/NS and TVCcontrol is the TVC value prior to NP/NS.
Data are expressed as means ±s.e.m. Statistical comparison of descriptive variables for traditional neck chamber and paired neck chamber groups were performed using Student's paired t tests. Statistical comparison of physiological responses (HR, MAP, SV, Q and TVC) to changes in ECSP between seated and supine positions were made utilizing a repeated measures two-way analysis of variance (ANOVA) with a 2 × 7 design (position × chamber pressure). A repeated measures one-way ANOVA was also used to compare the contributions of Q and TVC at the time of peak HR and MAP in the upright seated and supine positions. In all ANOVA analyses, a Student-Newman-Keuls test was employed post hoc when main effects were significant. Statistical significance was set at P < 0.05. Analyses were conducted using SigmaStat (Jandel Scientific Software, SPSS Inc., Chicago, IL, USA) for Windows.
Comparisons of carotid baroreflex function curve parameters between traditional neck chamber and paired neck chamber
A comparison of the logistic function parameters describing the carotid baroreflex control of HR and MAP are presented in Tables 1 and 2, respectively. No significant differences were found in the carotid-HR or carotid-MAP baroreflex function curve parameters between the traditional neck chamber and paired neck chamber in both the upright seated and supine positions.
Table 1. Comparison of carotid–HR baroreflex function curve parameters between the paired neck chamber and the traditional neck chamber
Values are means ±s.e.m.A1, range of response of the dependent variable (maximum–minimum); A2, gain coefficient; A3, centring point; A4, minimum response of HR; Gmax, maximal point on first derivative curve of logistic function (maximum gain); CSPthr, carotid sinus threshold pressure; CSPsat, carotid sinus saturation pressure. There were no significant differences for any of the parameters in carotid–HR baroreflex function curves when comparing the two chambers. * Significant differences between the seated and supine positions (P < 0.05).
A1 (beats min−1)
17.4 ± 1.9
17.1 ± 2.1
13.7 ± 1.6
14.5 ± 2.1
0.10 ± 0.02
0.12 ± 0.02
0.09 ± 0.01
0.10 ± 0.01
77.7 ± 2.9
74.8 ± 2.2
72.5 ± 4.0
72.9 ± 4.1
A4 (beats min−1)
55.3 ± 2.4
57.0 ± 2.6
47.6 ± 1.7*
46.7 ± 1.7*
Gmax (beats min−1 mmHg−1)
−0.40 ± 0.05
−0.40 ± 0.05
−0.31 ± 0.05
−0.34 ± 0.06
52.7 ± 4.9
49.9 ± 4.7
48.2 ± 5.3
48.3 ± 5.4
102.7 ± 4.5
100.7 ± 5.2
96.8 ± 4.2
97.6 ± 6.0
Table 2. Comparison of carotid–MAP baroreflex function curve parameters between the paired neck chamber and the traditional neck chamber
Values are means ±s.e.m.A1, range of response of the dependent variable (maximum–minimum); A2, gain coefficient; A3, centring point; A4, minimum response of MAP; Gmax, maximal point on first derivative curve of logistic function (maximum gain); CSPthr, carotid sinus threshold pressure; CSPsat, carotid sinus saturation pressure. There were no significant differences for any of the parameters in carotid–MAP baroreflex function curves when comparing the two chambers.
16.7 ± 1.4
16.2 ± 2.1
17.5 ± 1.6
16.9 ± 1.5
0.11 ± 0.01
0.12 ± 0.01
0.10 ± 0.01
0.10 ± 0.01
72.3 ± 1.7
70.4 ± 3.5
72.7 ± 3.4
73.0 ± 4.2
68.4 ± 2.0
66.7 ± 2.4
66.8 ± 1.9
66.8 ± 1.5
−0.43 ± 0.05
−0.41 ± 0.04
−0.42 ± 0.05
−0.41 ± 0.05
51.9 ± 1.9
49.5 ± 3.9
49.2 ± 4.8
50.0 ± 3.9
92.6 ± 3.0
91.1 ± 4.7
96.2 ± 5.0
96.0 ± 5.9
Operating Point (mmHg)
75.5 ± 1.7
73.9 ± 1.9
74.7 ± 1.5
73.8 ± 1.5
Carotid baroreflex control of cardiovascular variables
We examined multiple efferent carotid baroreflex responses including HR, MAP, SV, Q and TVC. Figure 1A, B and C summarize the HR, MAP and SV responses to changes in ECSP. Each NP and NS stimulus elicited a significant alteration in HR in both the upright seated and supine positions (P < 0.001). Compared with the supine position, the upright seated position resulted in a significantly higher HR at all carotid sinus pressures (P < 0.001). All NP and NS stimuli caused significant changes in MAP in both the upright seated and supine positions (P < 0.001), Fig. 1B. However, there were no significant differences in MAP responses between the upright seated and supine positions at any carotid sinus pressures (P= 0.942). No significant changes in SV were noted during the application of NP and NS in the upright seated and supine positions (P= 0.571), Fig. 1C. However, SV at any given ECSP was significantly lower in the upright seated position compared with the supine position at all carotid sinus pressures (P= 0.009).
Figure 2A and B summarize the Q and TVC responses to changes in carotid sinus transmural pressure. Each NP and NS stimulus elicited a significant alteration in Q in both the upright seated and supine positions (P < 0.001). However, there were no significant differences in the Q responses between the upright seated and supine positions at any carotid sinus pressure (P= 0.625), suggesting that the increase in baseline HR compensated for the reduced SV of the upright seated position. Similar to Q, all NP and NS stimuli caused significant alterations in TVC in both the upright seated and supine positions (P < 0.001), see Fig. 2B. No significant differences in TVC responses were found between the two positions at any carotid sinus pressure (P= 0.887).
Figure 3 provides the group averages for carotid baroreflex-mediated changes in MAP, TVC, TAC, Q and HR elicited by 5 s of +40 Torr NP in the upright seated position. The calculated predicted MAPQ, predicted MAPTVC and percentage contribution of Q and TVC to achieve the carotid baroreflex-mediated change in blood pressure during 5 s of +40 Torr neck pressure in the upright seated position are presented in Fig. 4. As noted, there was a time lag between the peak change in Q (group average 3.3 ± 0.5 s) and the peak change in MAP (6.3 ± 0.5 s) to +40 Torr NP (P < 0.05). Thus, at the time of the peak MAP response the percentage contribution of Q to the change in MAP was significantly lower (4 ± 15 %) than TVC (100 ± 18 %).
Figure 5 summarizes the percentage change in the contribution of Q and TVC to the carotid baroreflex-mediated changes in MAP in the upright seated and supine positions. The contribution of Q to the change in MAP was highest during the last three beats of the 5 s NS/NP stimulation, which corresponded with the peak HR response. However, after the 5 s NS/NP stimuli ceased, the contribution of Q decreased, and the contribution of TVC increased to a peak at approximately the same time as the peak MAP response. This temporal relationship between changes in Q and vascular conductance was maintained regardless of the amount of NP or NS used. There were no significant differences in the contributions of Q or TVC between different chamber pressures at the time of peak HR and MAP in both seated and supine positions. The responses in the supine position were qualitatively similar to those in the upright seated position. However, the carotid baroreflex-mediated changes in MAP at the time of the peak HR response was 32–48 % of the peak MAP response in the upright seated position and 53–68 % of the peak MAP response in the supine position. The percentage contribution of Q to the changes in MAP (±2 mmHg) at the time of peak HR was 165 ± 29 % in the upright seated position and 230 ± 51 % in the supine position. However, at the time of peak MAP response the percentage contribution of Q was only 0 ± 15 % in the upright seated position and 23 ± 17 % in the supine position. Overall, the percentage contribution of Q to the change in MAP at the time of peak MAP (±8 mmHg) was significantly lower than the contribution of TVC (P < 0.05) in both the upright seated and supine positions. In addition, the percentage contribution of TVC at the time of peak MAP in the upright seated position was significantly higher than that in the supine position (P < 0.05).
The major accomplishment of the present investigation was the beat-to-beat quantification of SV and subsequent assessment of the contribution of cardiac output (Q) and total vascular conductance (TVC) to the reflex-mediated change in blood pressure resulting from alterations in carotid sinus pressure. Since the brief periods of NS or NP did not alter stroke volume in the upright seated or supine position, the HR response was a true representation of the reflex-mediated changes in Q. More importantly, our findings indicated that alterations in vascular conductance were the primary means by which the carotid baroreflex responded to acute changes in carotid sinus pressure. However, changing posture from the seated to the supine position appeared to influence the mechanism by which the carotid baroreflex responded to NP/NS stimuli and caused a slightly greater reliance on carotid baroreflex-mediated changes in Q.
The peak changes in HR occurred within 2–3 s when MAP had changed approximately 2 mmHg, i.e. within one to two pulse intervals. This change in HR caused a subsequent change in Q that was responsible for the initial reflex-mediated changes in MAP, as SV was unaltered and TVC changed minimally or actually went in the opposite direction expected for baroreflex responses during these first few seconds. Hence, the percentage contribution of Q and TVC to the initial reflex-mediated changes in MAP was 165 ± 29 and −73 ± 31 %, respectively, in the seated position and 230 ± 51 and −143 ± 54 %, respectively, in the supine position (Fig. 4 and Fig. 5). It is probable that the initial opposite changes in TVC observed may be due to the dependence of the quantification of resistance and/or conductance on steady-state conditions, which clearly do not occur within the first few seconds of NP/NS. It is likely that during this time period (when arterial pressure is changing minimally) blood volume is accumulating in the arterial system due to its compliant properties. As such, the measured cardiac output overestimates the flow through resistance vessels and probably leads to the directionally opposite changes noted. Nevertheless, these data indicate that the contribution of vasomotor changes due to peripheral nerve activity resulting from the carotid baroreflex-mediated change in MAP were negligible in the first few seconds.
In contrast to HR, the peak changes in MAP in response to the application of NP or NS occurred 6–8 s after the initiation of the stimulus. The percentage contribution of Q and TVC to the peak change in MAP was 0 ± 15 and 95 ± 13 %, respectively, in the seated upright position and 23 ± 17 and 76 ± 17 %, respectively, in the supine position (see Fig. 5). At the time of peak MAP (6–8 s), the percentage contribution of TVC was reflective of the vasomotor responses due to the carotid baroreflex-mediated changes in peripheral nerve activity because Q was nearly at control values. Therefore, we suggest that most of the change in MAP at 6–8 s was due to the carotid baroreflex-mediated changes in SNA (Fadel et al. 2001). The carotid-HR latency of the peak response was similar in both seated upright and supine positions and are in agreement with previous findings (Potts & Raven, 1995). Regardless of position, the temporal relationship between changes in the contribution of Q and TVC were maintained across all NP and NS stimuli. The differences in proportional response of Q and TVC between the upright seated and supine positions were probably attributable to an increased baseline sympathetic nerve activity combined with a reduced central blood volume and SV in the seated upright position. Previously, the baseline muscle SNA of subjects seated upright compared to supine was reported to be increased (Burke et al. 1977) and was linked to the decreased central filling volume of the heart resulting in unloading of the cardiopulmonary baroreceptor and subsequent withdrawal of the central inhibition of sympathetic neural outflow (Ray et al. 1993; Vissing et al. 1994; Mano, 1996).
In agreement with the current findings, McKeown & Shoukas (1998) reported that changes in non-pulsatile carotid sinus pressure caused significant changes in arterial pressure, heart rate and total peripheral resistance, whereas no significant changes were observed in cardiac output and stroke volume in normotensive rats. Additionally, Brunner et al. (1984) demonstrated that there were potentially two types of interaction between carotid and aortic baroreflexes, which may act to control total peripheral resistance. Similar to the results of the present study, these investigators reported that both carotid and aortic arch pressure exhibited a sigmoidal relationship with arterial pressure that primarily reflected changes in total peripheral resistance. Moreover, Ohsumi & Scher (1992) indicated the importance of the control of vascular resistance by arterial baroreceptors after bilateral/unilateral carotid sinus or aortic baroreceptor denervation in conscious rabbits.
One advantage of these animal studies is the ability to directly measure cardiac output and peripheral resistance in more of a steady-state environment to evaluate carotid baroreflex function. However, this steady-state evaluation is difficult to reproduce in human investigations using NP/NS. In addition, O'Leary (1991) suggested that while neither resistance nor conductance was a perfect index of vasomotor responses, changes in conductance reflected the importance of the response in pressure regulation far better than changes in regional resistance. Therefore, we attempted to calculate the beat-to-beat changes in TVC and the contributions of Q and TVC to estimate the influence of both cardiac and vasomotor activities on blood pressure regulation during carotid baroreceptor stimulation in humans. An experimental protocol more likely to reflect the initial arterial baroreflex regulation that occurs at the beginning of an arterial pressure transient such as a change in posture. Also, we assume because of the parallel activity of the aortic and carotid baroreceptors that a selective modelling of the carotid baroreflex would be characteristic of arterial baroreflex as long as no interaction between the two baroreceptors was initiated (Eckberg et al. 1975; Eckberg, 1976, 1980; Potts & Raven, 1995).
Recently, Collins et al. (2001), using bilateral carotid occlusion in dogs, demonstrated that the reflex response to carotid baroreceptor stimulation was primarily due to peripheral vasoconstriction and they did not identify any alterations in cardiac output as being part of the reflex-mediated response. The data presented by Collins et al. (2001) reported the steady-state response achieved at 1.5–2 min following bilateral carotid occlusion. In the present investigation, we identified the immediate responses at the onset of carotid baroreceptor stimulation and clearly demonstrated that the initial (2–3 s) response reflected the carotid-cardiac input of the reflex in that > 100 % of the initial reflex alteration in blood pressure was due to changes in Q. However, the more predominant and longer lasting response to carotid baroreceptor stimulation was reflected in changes in TVC and confirms the data of Collins et al. (2001). Furthermore, both Potts et al. (1993) and Raven et al. (1997) had hypothesized that because the peak HR response occurred earlier than the peak MAP response, the peak HR and MAP data could be used independently to model the carotid-cardiac and carotid-vasomotor reflex arms of the carotid baroreflex, respectively. The data from the present investigation indicated their hypothesis to be correct and suggests that the carotid HR response can be used to assess the carotid-cardiac reflex, as SV does not change during NP/NS. Moreover, it appears that the carotid-MAP response primarily reflects a carotid-vasomotor reflex in that the MAP response was mainly due to reflex-mediated changes in TVC, a consequence of carotid baroreflex- induced changes in SNA, as demonstrated by Fadel et al. (2001).
Previously, during 500 ms changes in NP/NS from +40 to −65 Torr, Levine et al. (1990) acquired pulse-doppler measures of aortic blood flow velocity and reported no significant reflex-mediated changes in SV. As the use of the pulse-doppler probe was compromised by artifactual distortion of the flow velocity profile when used with the traditional neck chamber developed by Eckberg et al. (1975), we modified the simplified paired neck chamber, developed by Raine & Cable (1999), to enable a more accurate measurement of the flow velocity profile using a pulse-doppler flow probe. In addition, we extended the stimulus duration to 5 s to more completely assess carotid baroreflex-mediated changes in SV. Unfortunately, Raine & Cable (1999) did not compare responses of the same subjects to pressure changes applied with paired vs. traditional neck chambers. Therefore, we compared the responses induced by using both neck chambers to ensure the validity of our new paired neck chamber. The data presented in Tables 1 and 2 confirm the validity of the carotid baroreflex responses obtained using the traditional neck chamber or paired neck chamber in assessing the baroreflex response of humans.
The data of the present investigation indicate that the 5 s period of NP/NS stimulation did not elicit significant changes in SV of humans in either the seated or supine positions. These results confirm the data reported by Levine et al. (1990) in humans and Geerdes et al. (1993) in animals. Our findings suggest that at rest, SV changes have minimal influence in regulating ABP during carotid baroreceptor stimulation. Therefore, carotid baroreflex-mediated changes in HR were an important contributing factor to accomplish changes in Q. However, it is important to note that the carotid baroreflex has been reported to influence changes in SV under different stimulus conditions (Potts et al. 1996). In addition, baroreflex stimulation has been reported to affect changes in myocardial contractility (Iriuchijima et al. 1968; Kostiuk et al. 1976; Potts et al. 1996) and venous capacitance (Shoukas & Sagawa, 1973; Greene & Shoukas, 1986).
In the present investigation we utilized the difference between the upright seated position and the supine position as a means of unloading and loading the cardiopulmonary baroreceptors, respectively. Previous investigations have found that by unloading cardiopulmonary baroreceptors, forearm vascular resistance, muscle SNA and the maximal gain of the carotid baroreflex were increased (Pawelczyk & Raven, 1989; Vissing et al. 1994; Shi et al. 1996). Our data identified no differences between baseline TVC and reflex responses to NP/NS obtained in the seated upright or supine position despite the baseline stroke volumes (an index of cardiac filling volume) being significantly less in the upright seated position compared to the supine position. However, the absolute response of Q at the peak MAP was significantly greater in the supine position compared to the seated upright position suggesting that the carotid vasomotor arm of the reflex was more responsive to NP/NS in the seated upright position i.e. when the cardiopulmonary baroreceptors were unloaded. This would suggest that the supine position and its subsequent loading of the cardiopulmonary baroreceptors provided an increased sympathoinhibition (Burke et al. 1977; Ray et al. 1993; Vissing et al. 1994; Mano, 1996), which alters the mechanisms by which the carotid baroreflex responds to changes in carotid sinus pressure. However, the ability of the carotid baroreflex to regulate blood pressure appears to be unaltered by these postural changes, as there were no differences in the reflex-mediated changes in MAP between the upright seated and supine positions.
Potential limitations in the design and interpretation of the present investigation should be considered. First, with the application of NP/NS it is possible that the pressure transmitted to the carotid sinus may not be the same as the recorded external neck chamber pressure. However, Querry et al. (2001) directly measured transmission pressures using a balloon tipped (Millar) transducer placed under the fascia external to the carotid sinus and reported that correction of internal transmission resulted in minimal and non-significant changes in calculated carotid baroreflex parameters. Furthermore, findings suggested that the differences between animal and human experimental estimates of the maximal gain of the reflex was not a result of neck tissue dampening the transmission of the applied pressure, but was more probably a result of the anatomical and postural differences between species. Second, we recognize that the measurement of central venous pressure is necessary to calculate TVC and therefore, our absolute TVC values should be evaluated carefully. However, as central venous pressure was not altered during the application of NP/NS (Potts et al. 1993), the differences in absolute values of central venous pressure during supine and upright seated positions had no effect on the calculated baroreflex variables and their proportional responses. Any alterations in central blood volume were present prior to the start of any NP/NS stimulus and therefore, only contributed to baseline (i.e. prestimulus) haemodynamic differences manifested when assuming the supine and seated upright postures.
We conclude that alterations in vasomotor activity are the primary means by which the carotid baroreflex regulates ABP. Furthermore, since the brief periods of NP or NS did not alter stroke volume in the upright seated or supine position, the heart rate response was a true representation of the reflex-mediated changes in cardiac output. Also, it appeared that cardiopulmonary baroreceptor loading influenced the relationship between the contribution of Q and TVC to the carotid baroreflex-mediated change in MAP with an apparent greater reliance on carotid baroreflex-mediated changes in Q and thus, HR in the supine position compared with the upright seated position. Nevertheless, in both seated and supine positions the changes in MAP were primarily mediated by alterations in total vascular conductance.
We appreciate the laboratory support provided by Selena Godoy and David Keller, and the secretarial support in preparation of the manuscript by Lisa Marquez. We also sincerely thank the subjects for their interest and co-operation. This study was supported in part by the National Institutes of Health (NIH) Grant HL45547 and by the National Life Sciences Division of the National Aeronautics and Space Administration (NASA) of the United States under grant NAG5–4668.