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J Appl Physiol 95: 1789-1798, 2003. First published July 25, 2003; doi:10.1152/japplphysiol.01019.2001
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Change in spontaneous baroreflex control of pulse interval during heat stress in humans

Kichang Lee, Dwayne N. Jackson, Douglas L. Cordero, Takeshi Nishiyasu, Jochen K. Peters, and Gary W. Mack

John B. Pierce Laboratory and Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06519

Submitted 5 October 2001 ; accepted in final form 7 June 2003


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 
Spontaneous baroreflex control of pulse interval (PI) was assessed in healthy volunteers under thermoneutral and heat stress conditions. Subjects rested in the supine position with their lower legs in a water bath at 34°C. Heat stress was imposed by increasing the bath temperature to 44°C. Arterial blood pressure (Finapres), PI (ECG), esophageal and skin temperature, and stroke volume were continuously collected during each 5-min experimental stage. Spontaneous baroreflex function was evaluated by multiple techniques, including 1) the mean slope of the linear relationship between PI and systolic blood pressure (SBP) with three or more simultaneous increasing or decreasing sequences, 2) the linear relationship between changes in PI and SBP ({Delta}PI/{Delta}SBP) derived by using the first differential equation, 3) the linear relationship between changes in PI and SBP with simultaneously increasing or decreasing sequences (+{Delta}PI/+{Delta}SBP or -{Delta}PI/-{Delta}SBP), and 4) transfer function analysis. Heat stress increased esophageal temperature by 0.6 ± 0.1°C, decreased PI from 1,007 ± 43 to 776 ± 37 ms and stroke volume by 16 ± 5 ml/beat. Heat stress reduced baroreflex sensitivity but increased the incidence of baroreflex slopes from 5.2 ± 0.8 to 8.6 ± 0.9 sequences per 100 heartbeats. Baroreflex sensitivity was significantly correlated with PI or vagal power (r2 = 0.45, r2 = 0.71, respectively; P < 0.05). However, the attenuation in baroreflex sensitivity during heat stress appeared related to a shift in autonomic balance (shift in resting PI) rather than heat stress per se.

baroreceptors; thermoregulation; blood pressure regulation

THE AUTONOMIC NERVOUS SYSTEM'S response to heat stress is driven by sensory inputs from central and peripheral thermoreceptors that feed into the thermoregulatory center in the hypothalamus. Even though baroreceptors have no primary role in the generation of the differential vasomotor responses to heat stress (2), baroreceptors continuously modulate their activities in response to the change in blood pressure during heat stress (21). The addition of heat stress adds complexity to cardiovascular control mechanisms. Increased risk of orthostatic intolerance during heat stress has led to the proposal that blood pressure regulatory reflexes are attenuated. Convincing evidence exists to support a reduction in the baroreflex control of vasomotor tone during heat stress (3, 4, 22, 23, 25, 31). However, the impact of heat stress on baroreflex control of heart rate (HR) appears unclear (3, 4, 10, 23, 30, 33).

Several studies have assessed baroreflex activity in animals and in humans during heat stress. Gorman and Proppe (10) showed that a 2.6°C increase in core temperature in the baboon caused an upward shift of the baroreflex curve but no change in the slope of the HR-arterial blood pressure relationship (or baroreflex sensitivity) around the operating point. Baroreflex control of HR has been reported to increase (30) and decrease (23) with increasing core temperature in rats. These inconsistent results in animal studies are also evident in human studies. Yamazaki and Sone (33) found that whole body heating did not change baroreflex control of HR in humans. Crandall (3) reported no change in the gain of carotid-cardiac baroreflex curve during whole body heating but later reported (4) a decrease in the transfer function gain in the high-frequency range, indicating a decrease in dynamic baroreflex control of HR.

The inconsistencies in the previous studies could be attributed to a variety of factors ranging from species differences, age, the method of body heating, the magnitude of imposed heat stress, or the techniques used to assess baroreflex function. For example, Crandall (3) noted that the gain of the carotid-cardiac baroreflex curve was unchanged when the carotid-cardiac baroreflex curve was plotted as HR vs. carotid sinus pressure; however, the author found a 50% reduction in gain when pulse interval (PI) was used as an index of cardiac activity rather than HR.

Whereas the intensity of imposed heat stress to both animals and humans varied in previous studies, all the studies used whole body skin heating to force an increase in body temperature. This heating technique produces high skin temperatures and marked cutaneous vasodilation. In addition, even though cutaneous vascular resistance is decreased during heat stress, none of the earlier studies attempted to account for the impact of peripheral blood pooling on baroreflex function.

The purpose of this study was to investigate changes in baroreflex control of PI during heat stress. To overcome some of the potential limitations of earlier experimental designs, we implemented a number of specific experimental interventions. First, to increase body core temperature (~0.5°C), a lower leg immersion heating protocol was used that allowed mean skin temperature to change <1°C. This provided an alternative model to study the interaction between baroreflexes and thermoregulation. Second, spontaneous baroreflex control of PI was examined during heat stress with and without application of lower body positive pressure (LBPP) to help identify the impact of peripheral blood pooling during passive heating on spontaneous baroreflex control of PI. In addition, we estimated baroreflex sensitivity [the slope of the linear relationship between PI and systolic blood pressure (SBP)], when SBP was forced to decrease during application of -60 mmHg lower body negative pressure (LBNP). Finally, we report specific changes to the standard analysis of sequence data that improve the power of spontaneous baroreflex activity to assess baroreflex sensitivity.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 
Subjects

Nineteen healthy adult subjects (11 men, 8 women) aged 28 ± 7 yr volunteered to participate in this study. On a separate day, before the experiment, all subjects were familiarized with the experimental procedures. All studies were performed at the same time of day at 8:00 AM. The female subjects were tested during the early follicular phase of the menstrual cycle (days 1–4). The experimental protocol was approved by the Yale University School of Medicine Human Investigation Committee, and each subject was thoroughly acquainted with all aspects of the experiment before informed, written consent was obtained.

Experimental Protocol

Experiments were conducted in an environmental chamber controlled at a temperature of 27.0 ± 0.1°C. After entering the test chamber, the subjects rested in the supine position with the lower half of the body in a lower body pressure unit sealed at the level of the iliac crest by use of a flexible neoprene skirt. A custom-made water bath was placed inside the lower body pressure unit. Subjects bent their knees slightly (<20° above the horizontal plane of the hip) and immersed the lower legs in the 34°C water bath for 30–45 min during instrumentation. In all experiments subjects were allowed to relax for 15 min before they began a 5-min period of paced breathing (12 breaths per min) while beat-by-beat measures of SBP and PI were collected. After the data-collection period, all subjects were then passively heated for 30 min by raising the lower leg water bath temperature to 44°C. Within 25–30 min, body core (esophageal) temperature reached a new plateau and another 5-min data collection was performed. Data for the first eight subjects were collected as part of a series of experiments designed to evaluate baroreflex control of skin blood flow (28). In addition to measurement of spontaneous variations in PI and SBP, we were able to analyze beat-by-beat changes in PI and SBP during application of -60 mmHg LBNP. LBNP was applied at -1.0 mmHg/s and was maintained for 2 min at -60 mmHg. For each subject, the linear relationship between PI and SBP was determined during application of -60 mmHg LBNP when SBP fell in a progressive manner. This generally occurred during the first minute of application of -60 mmHg LBNP and constituted ~10–20 s of data. During the heating protocol for the initial eight subjects, we noted a small yet significant decrease in central venous pressure. As such, we began a second series of experiments that incorporated an additional 5-min period of paced breathing with the application of +20 mmHg LBPP in attempt to reverse the impact of heating on the reduction in central blood volume. In this second series of experiments (n = 11), +20 mmHg LBPP was applied at a rate of 0.7 mmHg/s and the data in this transitional period were excluded from data analysis. During all data-collection periods, the subjects synchronized their breathing to a metronome set to a cadence of ~12 breaths per minute (0.2 Hz).

Measurements

Body temperature. Body core temperature was measured by use of a thermocouple inserted through a nostril into the esophagus to the approximate level of the heart. Insertion depth was calculated as 25% of subject's standing height. Skin temperature was monitored by using surface thermocouples placed at seven sites, and mean skin temperature was calculated by using the following regional percentages: abdomen 28%, chest 10%, forehead 21%, forearm 6%, upper arm 12%, anterior thigh 15%, and lateral calf 8%. The weighting of each site is based on the product of regional area (11) and local relative thermal sensitivity (24).

Cardiovascular variables. Arterial blood pressure was continuously recorded from the middle digit of the left hand by the Peñáz method (Ohmeda Finapres 2300, Louisville, CO), and, simultaneously, arterial blood pressure was also assessed from the right arm every minute by automated brachial auscultation (Colin STBP model 780B, Aichi, Japan). The literature supports the use of finger blood pressure in tracing beat-by-beat changes in central SBP and its use in frequency-domain analysis (16). In addition, our experimental design (thermoneutral conditions and mild heat stress) provides conditions that minimize the absolute overestimation of central SBP by the Finapres. Stroke volume (SV) was determined noninvasively by impedance cardiography (Minnesota Impedance cardiograph model 304-B, Minneapolis, MN) using the ensemble average of 25 s of cardiac cycles. HR and PI were determined beat to beat from lead II of an ECG recording, and cardiac output (CO) was calculated by multiplying HR and SV.

Data Analysis

Data were continuously digitized and stored in data files on a personal computer. Finapres blood pressure and ECG were recorded with an eight-channel computerized data-acquisition system at a sampling rate of 400 Hz (ADInstruments MacLab 8e, Castle Hill, Australia). Beat-by-beat diastolic blood pressure (DBP) and SBP, HR, and PI were determined by use of peak detection algorithms developed in this laboratory using Matlab software (Mathworks, Natick, MA). All detected signals were manually inspected to confirm that there were no missing data.

Spontaneous baroreflex function was evaluated by multiple techniques to disclose possible changes in baroreflex control of PI during heat stress (Fig. 1). First, the slope of the linear relationship between PI and SBP (baroreflex sensitivity) was determined whenever a baroreflex sequence (three or more consecutive beat-to-beat increases in PI with a simultaneous increase in SBP or three or more consecutive beat-to-beat decreases in PI with a simultaneous decrease in SBP) was identified (1). Linear regression analysis was applied to each baroreflex sequence. Only those sequences in which the correlation between PI and SBP was >0.85 were accepted. The average of the individual baroreflex slopes in each thermal condition was taken as a measure of spontaneous baroreflex sensitivity. The incidence of baroreflex sequences is reported as sequences per 100 pulses to normalize for differences in HR. Also, the total number of heartbeats involved in baroreflex responses is reported as an absolute pulse number and as a percentage of the total heart beats within a given 5-min measurement period. Baroreflex sequences were identified using programs developed in our laboratory by use of Matlab software.



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  		Fig. 1. Representative data from 1 subject demonstrating the attenuation of spontaneous baroreflex control of pulse interval during heat stress. A: extraction of baroreflex sequences from the 5-min data set and the mean slope of these baroreflex sequences. B: calculated baroreflex sensitivity based on all the beat-by-beat changes in pulse interval and systolic blood pressure during the entire 5-min collection period. This latter analysis would include both baroreflex and nonbaroreflex sequences. In this example we see a small decrease in systolic blood pressure with heat stress.

 

Beat-by-beat PI and SBP data were further processed to estimate baroreflex sensitivity during each experimental condition as described by Frankel et al. (6). Changes in PI and SBP were derived by using the first differential equations

where n = 2nd, 3rd,... heartbeats.

These data were screened for noise and artifacts, and data were excluded if |{Delta}PI| >= 1,000 ms or |{Delta}SBP| >= 30 mmHg. After data screening, the linear relationship between {Delta}PI and {Delta}SBP ({Delta}PI/{Delta}SBP) was studied by use of geometric mean regression analysis. The slope of the regression was taken as an index of spontaneous baroreflex sensitivity (Frankel method). This method uses 100% of the available data and does not discriminate between baroreflex ({Delta}PI and {Delta}SBP increase or decrease together) and nonbaroreflex sequences ({Delta}PI and {Delta}SBP change in opposite directions).

We modified the analysis described by Frankel et al. (6) so that we used only beat-to-beat changes in both PI and SBP when they simultaneously increased (+{Delta}PI/+{Delta}SBP) or decreased (-{Delta}PI/-{Delta}SBP) (identified throughout as "modified Frankel method"). Total number of heartbeats involved in assessment of the baroreflex response is reported as an absolute pulse number and percentage of the total heart beats within the 5-min collection period.

Assessments of baroreflex sensitivity during spontaneous fluctuations in SBP were compared with baroreflex sensitivity calculated when SBP was forced to decrease during application of -60 mmHg LBNP. Arterial blood pressure usually fell during the first minute of application of -60 mmHg LBNP. The slope of the linear relationship between PI and SBP during the period when SBP falls (~10–20 s of data) was used as an estimate of baroreflex sensitivity. For comparison purposes, the estimates of baroreflex sensitivities were also calculated by using HR instead of PI for all analyses we performed.

Autonomic system response to each experimental condition was assessed with a fast Fourier transform-based algorithm (Welch's periodogram) of PI variability using a stationary 256 data points with application of Hanning window (Mathworks). The spectrum associated with different frequency bands of response was calculated by integrating the amplitude of the spectrum over the desired frequency range (11a). Total power was defined as the area under the spectrum for the frequencies <=0.5 Hz. The spectrum displayed a high power at 0.2 Hz corresponding to breathing frequency, and the area under the spectrum from 0.15 to 0.4 Hz [high-frequency component (HF)] was used as an index of cardiac parasympathetic activity and the log2 of this area was defined as vagal power. The low-frequency component (LF, 0.04 to 0.15 Hz) was identified, and the LF/HF ratio was used as an index of sympathovagal balance (26). Spectral components are presented both in absolute values of power (ms2/Hz) and normalized units representing the relative value of LF or HF in proportion to the total power minus the very-low-frequency component (11a). Transfer function analysis was performed on SBP and PI at both the LF and HF of the power spectral plot as described by Saul et al. (29). Cross-spectral density of SBP and PI divided by the power spectral density of SBP was used to estimate transfer function gain (units = ms/mmHg).

Statistics

Data were compared by use of a two-way ANOVA with repeated measures. The factors used in the analysis were thermal stage (thermoneutral vs. heat stress) and pressure (with or without LBPP). If a significant interaction was observed, simple effects analysis with the Bonferroni adjustment was used to examine specific pairwise differences. All values are presented as means ± SE for the specific number of subject in each comparison group. Statistical significance was accepted at P < 0.05.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 
Temperature and Cardiovascular Responses

A summary of the body temperature and cardiovascular responses to passive heating is presented in Table 1. During heat stress, mean skin temperature increased 0.9 ± 0.1°C (P < 0.05) and body core temperature increased 0.6 ± 0.1°C (P < 0.05). During application of +20 mmHg LBPP, mean skin temperature decreased (Table 1, P < 0.05). The decrement in skin temperature was associated with a decrease in skin temperatures below the iliac crest (site of seal for pressure box) averaging 0.2 ± 0.1 and 0.3 ± 0.1°C during thermoneutral and heat stress conditions, respectively.


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  		Table 1. Cardiovascular and body temperature parameters before and after passive heating

 

Passive heating decreased SV (P < 0.05) but the increase in HR resulted in a 1.4 ± 0.5 l/min increase in CO (P < 0.05). Mean arterial pressure was unchanged by heat stress. PI decreased 23 ± 2% from 1,007 ± 43 to 776 ± 37 ms with passive heating (P < 0.05). Application of +20 mmHg LBPP increased DBP during thermoneutral condition and SBP, DBP, and mean arterial pressure during the passive heating. In addition, during passive heating application of +20 mmHg LBPP increased PI and SV (P < 0.05).

Spontaneous Baroreflex Sensitivity

The impact of passive heating on spontaneous baroreflex function is summarized in Tables 2 and 3. In the thermoneutral condition, spontaneous baroreflex sensitivity based on standard sequence methodology averaged 15.0 ± 1.8 ms/mmHg at rest, and it decreased to 10.1 ± 1.0 ms/mmHg during heat stress (n = 19, P < 0.05). Spontaneous baroreflex sensitivity described by the Frankel method was not significantly altered by heat stress, averaging 10.1 ± 3.9 ms/mmHg during thermoneutral conditions and 10.1 ± 1.4 ms/mmHg during heat stress. When the baroreflex sensitivity was assessed by using the modified Frankel method (+{Delta}PI/+{Delta}SBP or -{Delta}PI/-{Delta}SBP), it was significantly attenuated from 18.4 ± 1.8 ms/mmHg at rest to 9.9 ± 1.1 ms/mmHg during heat stress. The same analysis performed using HR instead of PI showed no impact of heat stress on baroreflex sensitivity.


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  		Table 2. Index of baroreflex sensitivity assessed by progressive increases or decreases in pulse interval and systolic blood pressure over 3 or more consecutive beats

 

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  		Table 3. Index of baroreflex sensitivity assessed by beat-by-beat changes in pulse interval and systolic blood pressure

 

Forced reductions in SBP during application of LBNP resulted in an average slope of the PI-SBP relationship of 7.7 ± 8.9 ms/mmHg. During heat stress the slope of the PI-SBP relationship decreased to 4.3 ± 2.6 ms/mmHg (Fig. 2, P < 0.05). The same analysis performed using HR instead of PI resulted in similar slopes of the HR-SBP relationship during thermoneutral (-0.67 ± 0.14 beat/mmHg) and heat stress conditions (-0.60 ± 0.08 beat/mmHg).



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  		Fig. 2. Representative data from 4 subjects showing the attenuation of the pulse interval-systolic blood pressure relationship (baroreflex sensitivity) during a forced reduction in systolic blood pressure during -60 mmHg of lower body negative pressure. The change in baroreflex sensitivity during heat stress in subjects 1 (A) and 3 (C) appears to resemble a shift in the operating points on the same stimulus-response curve. The data in subjects 2 (B) and 4 (D) represent shifts to different stimulus-response curves.

 

The number of baroreflex sequences averaged 5.2 ± 0.8 sequences per 100 heartbeats involving 22 ± 3% of the total heartbeats. Passive heating increased the number of baroreflex sequences to 8.6 ± 0.9 sequences per 100 heartbeats, encompassing 37 ± 4% of total heartbeats (Table 2, P < 0.05). In the modified Frankel method, the total number of heartbeats used in the analysis was unchanged by heat stress and averaged ~60%.

Application of +20 mmHg LBPP had little impact on baroreflex sensitivity or number of baroreflex sequences per 100 heartbeats (Tables 2 and 3). However, during heat stress, baroreflex sensitivity tended to increase (P = 0.07) with application of +20 mmHg LBPP (Table 3). Spontaneous baroreflex sensitivity expressed in beats per millimeters of mercury was unchanged by heat stress or LBPP.

Autonomic Nervous System Responses

Heat stress caused significant changes in the power spectral densities for PI variability. Specifically, total power and both LF and HF decreased in absolute power (Table 4, P < 0.05). When spectral components are normalized for the drop in total power, we see that heat stress caused an increase in the LF (P < 0.05) and a decrease in the HF (P < 0.05). The ratio of low- to high-frequency power was increased (P < 0.05) and vagal power was decreased (P < 0.05) during heat stress. Transfer function gain based on cross-spectral density of SBP and PI decreased 40% in the high-frequency range with heat stress (Table 4, P < 0.05). Transfer function gain based on cross-spectral density of SBP and HR showed a similar reduction in the high-frequency range during heat stress (Table 4, P < 0.05). Application of +20 mmHg LBPP had no signifi-cant impact on spectral analysis of PI variability or transfer gain estimates (Table 4).


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  		Table 4. Spectral analysis of pulse interval variability and baroreflex sensitivity assessed by transfer function estimate

 

Changes in spontaneous baroreflex sensitivity during heat stress were not correlated with the changes in arterial blood pressure (SBP, DBP, or mean arterial pressure). However, baroreflex sensitivity assessed by standard sequence techniques and the modified Frankel method were correlated with PI (r2 = 0.26 and r2 = 0.45, respectively, P < 0.05). Spontaneous baroreflex sensitivity was significantly correlated with estimates of vagal power when estimated by the standard sequence methodology, (r2 = 0.47, P < 0.05) or the modified Frankel method (r2 = 0.71, P < 0.05; Fig. 3).



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  		Fig. 3. Curvilinear relationship between spontaneous baroreflex sensitivity and vagal power (r2 = 0.71, P < 0.05). HF, high-frequency component of power spectral density plot. LBPP, +20 mmHg of lower body positive pressure.

 


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 
During heat stress, baroreflex-mediated changes in vaso- and venomotor tone and HR act in concert to minimize the fall in SV to help regulate arterial blood pressure. A deficit in any of these reflex arcs will contribute to orthostatic intolerance during heat stress. A significant finding of this study is that the occurrence of baroreflex sequences increased during heat stress. This observation implies that a reduced ability to maintain blood pressure during heat stress is not because the baroreceptor system is not actively engaged but rather reflects how effectively the system works. In addition, heat stress caused a reduction in baroreflex sensitivity, defined as the slope of the linear relationship between changes in PI and SBP. This reduction in baroreflex sensitivity was confirmed by four separate analysis techniques: 1) standard baroreflex sequence analysis (1, 7, 13) that used only 20% of the available heartbeats, 2) a modified baroreflex sequence analysis (see METHODS) that used considerably more (60%) of the available heartbeats by calculating changes in both PI and SBP when they simultaneously increased (+{Delta}PI/+{Delta}SBP) or decreased (-{Delta}PI/-{Delta}SBP), 3) changes in PI and SBP when arterial blood pressure was forced to decrease with application of -60 mmHg LBNP, and 4) transfer gain estimates (4, 17). The change in baroreflex sensitivity was strongly correlated with the change in resting PI and vagal power. One interpretation of these data is that the reduction in baroreflex sensitivity during heat stress is due, in part, to a reduction in vagal tone. The impact of peripheral venous pooling on baroreflex sensitivity was negligible because application of +20 mmHg LBPP had no impact on the slope of the PI-SBP relationship during heat stress.

One interpretation of our data is that baroreflex sensitivity (the slope of the PI-SBP relationship) decreased with heat stress. This interpretation depends on the acceptance of certain assumptions. First, we have used PI, as opposed to HR, to evaluate baroreflex sensitivity. In this study, estimates of baroreflex sensitivity based on HR show little change with heat stress. The hyperbolic relationship between PI and HR has always evoked controversy regarding the interpretation of baroreflex function. Specifically, evaluating baroreflex sensitivity has often led to different interpretations depending on whether the authors used PI or HR (3, 17). However, animal studies demonstrate that PI varies in direct proportion with vagal stimulation (19). These data support the idea that PI is an accurate index of cardiac vagal activity and is an appropriate index to use when estimating baroreflex sensitivity. All analysis techniques using PI showed a reduced baroreflex sensitivity with heat stress. Specifically, our estimates of baroreflex sensitivity based on baroreflex sequence analysis, modified Frankel analysis, forced reductions in SBP with -60 mmHg LBNP, and transfer function analysis all demonstrate a reduction in baroreflex sensitivity with heat stress.

A review of studies using spontaneous variations in PI and SBP to estimate baroreflex sensitivity indicates that baroreflex sensitivity is proportional to resting PI, regardless of the nature of the resting PI (i.e., age, gender, tilt, or LBNP) (5, 7, 9, 12–15, 18, 27). In this study, we found a significant correlation between PI and baroreflex sensitivity. Thus, whereas we observe a reduction in baroreflex sensitivity with heat stress, this response appears related to the shift in resting PI rather than heat stress per se.

Another assumption associated with evaluation of spontaneous baroreflex response is that the analysis has sufficient fidelity to identify small changes in baroreflex function. Analysis of spontaneous baroreflex sequences is limited by the incidence rate of these sequences. Typically, this analysis uses only ~20% of the available heartbeats within a 5-min collection period. For example, we observed that four subjects with low HR (53 ± 1 beats/min) had less than 10 baroreflex sequences during thermoneutral conditions. Under conditions of a low resting HR we are likely to bias the analysis of baroreflex sensitivity. On the other hand, using every beat to estimate baroreflex sensitivity (Frankel method, Ref. 6) is also limited by inclusion of what others have called "nonbaroreflex sequences." We modified the Frankel method to use only changes in PI and SBP that either increase or decrease together. This change in the analysis technique allowed us to use ~60% of the available heartbeats. This modified Frankel method had more power than the standard baroreflex sequence analysis. This would account for the inability of the latter technique to detect a reduction in baroreflex sensitivity with heat stress when the number of subjects was limited to n = 11 (Table 2) but could identify a significant reduction when n = 19. The modified Frankel technique identified the reduction in baroreflex sensitivity with heat stress in all conditions (Table 3). As such, the analysis of baroreflex sensitivity using baroreflex sequence analysis is limited by the low number of heartbeats used within the analysis. Longer recording periods may provide more sequences for analysis and improve the power of this analysis. Many of the earlier studies using estimates of baroreflex sensitivity that used baroreflex sequence analysis used 5-min recording periods for only 8–10 subjects (10, 23). On the basis of our data, these studies may not have had sufficient power to detect a change in baroreflex sensitivity associated with heat stress.

The spontaneous baroreflex methodology examines a limited range of changes in SBP. As such, a complete stimulus-response curve cannot be evaluated. However, our analysis of changes in PI and SBP during -60 mmHg LBNP supports the idea that heat stress causes a reduction in baroreflex sensitivity. We cannot determine whether the change in slope of the baroreflex function is due simply to a change in PI and a shift in the operating point or whether there is a real change in the slope at a given PI. Figure 2 illustrates the kind of changes on the PI-SBP relationship during application of -60 mmHg LBNP in thermoneutral and heat stress conditions. On the basis of the response of subjects 1 and 3, we might speculate that the shift in slope during heat stress was the result of a shift in the operating point on the same stimulus response curve. However, the response of subjects 2 and 4 does not support this interpretation.

Previous work on the impact of heat stress on baroreflex control of HR has provided conflicting results. Whole body heating, induced by skin heating using a liquid-perfused garment, did not change spontaneous baroreflex control of HR (33) or gain of the carotid-cardiac baroreflex curve (3). In this latter study, Crandall (3) noted the fact that the gain of the baroreflex was attenuated with PI as a dependent variable. Consistent with this interpretation, Crandall et al. (4) reported that whole body heating decreased the transfer function gain in the high-frequency range, reflecting a decrease in dynamic baroreflex control of HR. Our results are consistent with the latter work by Crandall et al. In addition, we observed that the reduction in baroreflex sensitivity during heat stress is associated with a concomitant decrease in the HF (0.15 to 0.4 Hz) of the power spectral density plot of PI variability.

On the basis of the results of this study, we can suggest that heat stress contributes to the reduction in baroreflex sensitivity in two ways. First, changes in autonomic balance will both impact resting HR and alter vagal-mediated baroreflex sensitivity (20). Table 4 clearly shows the shift in autonomic balance during heat stress. The combined effect of a decrease in the normalized HF component (vagal activity) and the increase in the LF/HF ratio (sympathetic activity) provide evidence of a shift in autonomic balance that results in an increase in HR. We also note a strong correlation between PI or vagal tone and baroreflex sensitivity (Fig. 3). However, this alteration in baroreflex sensitivity may not be attributed to heat stress, per se, but to the shift in autonomic balance caused by heat stress. Second, in animal models the stimulation of hypothalamic nuclei acts to inhibit vagal bradycardia induced by baroreceptor loading (8). It is possible that the increase in body core temperature during heat stress will activate hypothalamic nuclei and contribute to a reduction in baroreflex sensitivity. We noted an inverse relationship between the increase in body core temperature and the decrease in baroreflex sensitivity (r2 = 0.47, P < 0.05). However, these latter data provide meager support for the hypothesis that afferent input to hypothalamic nuclei from thermal receptors contribute to attenuated baroreflex control of PI during heat stress.

In conclusion, baroreflex control of PI assessed by several different techniques provides consistent evidence of a reduction in baroreflex sensitivity during heat stress. Our interpretation is biased by the use of PI rather than HR as our index of vagal modulation of cardiac activity. A reduction in transfer function gain between HR (or PI) and SBP supports a reduced coupling between changes in SBP and cardiac activity during heat stress. The cardiovascular adjustments to heat stress include a shift in the cardiac sympathovagal balance to reduced vagal and increased sympathetic components. It is likely that this modulation of autonomic balance contributes to an attenuated baroreflex control of PI during heat stress. This conclusion is based on the use of PI as an appropriate index of vagal modulation of cardiac activity. Whereas the ability to adjust PI in response to spontaneous changes in arterial blood pressure may be attenuated during heating the occurrence of baroreflex sequences is increased. Thus arterial baroreflexes are clearly active during heat stress but appear less effective in adjusting PI for a given change in arterial blood pressure. The attenuation in baroreflex function during heating is consistent with the known effects of changes in sympathovagal balance on vagal inhibitory activity. It remains unclear whether the inhibitory effect of hypothalamic stimulation on vagal inhibitory responses contributes to the reduction in baroreflex sensitivity with heat stress.


   DISCLOSURES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
ACKNOWLEDGMENTS
 REFERENCES
 
This work was supported by National Heart, Lung, and Blood Institute Grant HL-39818.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
REFERENCES
 
We thank the volunteer subjects for their time and cooperation. Also, we thank Dr. Christopher Cheatham for valuable comments.


   FOOTNOTES
 

Address for reprint requests and other correspondence: G. W. Mack, John B. Pierce Laboratory, 290 Congress Ave., New Haven, CT 06519 (E-mail: mack{at}jbpierce.org).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
 ACKNOWLEDGMENTS
 REFERENCES
 

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