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a Laboratory of Applied Physiology, Graduate School of Human and Environmental Studies, Kyoto University, Japan
Toshio Moritani, FACSM, Graduate School of Human & Environmental Studies, Kyoto University, Laboratory of Applied Physiology, Sakyo-ku, Kyoto 606-8501, Japan E-mail: moritani{at}virgo.jinkan.kyoto-u.ac.jp.
| Abstract |
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Methods. We performed an incremental submaximal exercise test in 24 healthy, older men aged 6070 years. They were divided into physically fit (PF, oxygen uptake at anaerobic threshold [AT
O2] = 25.2 ± 0.85 ml·kg-1·min-1) and physically unfit (PU, AT
O2 = 19.6 ± 0.42 ml·kg-1·min-1) groups, based upon the results of an incremental exercise stress test. The cardiac autonomic nervous system (ANS) activities were assessed by means of power spectral analysis of heart rate variability. Baroreflex sensitivity (BRS) testing was performed using simultaneous beat-by-beat blood pressure and heart rate measurement during a transition from supine horizontal position to 60° head-up-tilting (HUT).
Results. At rest conditions, the high-frequency component ( p = .03) and total power ( p = .04) of heart rate variability spectrum were significantly higher in the PF group. The BRS assessed during passive HUT was also significantly higher (7.5 ± 0.5 vs 3.0 ± 0.4 ms·mm Hg-1, p = .001) in the PF compared with the PU group. In addition, a significant correlation coefficient (r = .73, p = .001) was found between AT
O2 and BRS among the subjects.
Conclusions. The maintenance of high cardiorespiratory function, i.e., higher AT
O2 through a life-long active lifestyle including endurance exercise, may play an important role in reserving cardiac ANS and BRS in older men.
AGING leads to changes in cardiac autonomic functions. This is manifested by decreased parasympathetic influence on the heart (1), reduced cardiac responsiveness to ß-adrenergic stimulation (2), and decreased baroreflex sensitivity (BRS) (3). Multiple mechanisms are involved in the decline in BRS with advancing age. It has been characterized by a decrease in sensitivity of baroreceptor-heart rate reflex (4), reduced preloading, greater stiffness (a reduced compliance), increased average systolic blood pressure (SBP), and decreased intrinsic sino-atrial node functions (5).
Previous studies have demonstrated that, in myocardial infarction and heart failure, diminished BRS and heart rate variability (HRV) are both associated with increased mortality (6)(7). Furthermore, in an elderly community-based cohort of the Framingham study, the decrease in cardiac autonomic modulation with aging was associated with an increased risk of cardiac events in clinically disease-free individuals, even after adjusting for other known risk factors (8). It is assumed that a decrease in cardiac autonomic modulation with low parasympathetic nervous system (PNS) activity may decrease the fibrillation threshold and thus predispose to ventricular fibrillation (9). Thus, there is growing interest in the effects of cardiorespiratory fitness on improvement of cardiac autonomic functions. The findings of a number of studies (10)(11) have provided support for the association of cardiorespiratory fitness and enhanced BRS; however, not all of the studies are in agreement (12)(13).
Although autonomic nervous system (ANS) activities and BRS in young people and athletes have been widely studied, little is known about these functions in physically active older adult men. Davy and colleagues (14) reported that there is an inevitable decline in HRV and BRS in sedentary and physically active women. However, HRV and BRS were higher in physically active women, at any age. The question remains whether or not decreased cardiorespiratory fitness level is related to the decline of baroreceptor sensitivity in healthy older men. In the present study, we investigated the association between cardiorespiratory fitness level and cardiac ANS activities in conjunction with BRS in healthy older men using beat-by-beat measurement of HRV power spectral analysis and BRS measurement during passive head-up-tilting, respectively.
Because the primary function of baroreflex is acute blood pressure (BP) regulation, including that caused by postural changes, which requires a major demand of system to keep the homeostasis, we evaluated BRS using experimentally induced orthostatic challenges to cardiovascular mechanism. Specifically, during the passive tilting, the decrease in BP is thought to cause immediate heart rate (HR) acceleration through sympathetic stimulation mediated by withdrawal of vagal tone (15), evoked by pressure changes at the baroreceptors. This method has been reported in many studies (16)(17) and has been proven as a reliable noninvasive method for quantitative and qualitative assessment of BRS in human subjects.
| Methods |
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All subjects were normotensive (BP <140/90 mm Hg) with no history of syncope or varicose veins. Also, they were free of cardiopulmonary disease assessed by medical history and by electrocardiogram at rest and during an incremental exercise test. Because older individuals exercising regularly may not always show high cardiorespiratory fitness because walking, the most common exercise modality among our subjects, does not sometimes sufficiently increase maximal oxygen uptake or oxygen uptake at anaerobic threshold (AT
O2), we decided to separate the subjects into physically fit (PF, n = 12) and physically unfit (PU, n = 12) groups based on the results of the progressive exercise stress test. The subjects' anthropometrical and cardiorespiratory fitness data are presented in Table 1 .
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Determination of Anaerobic Threshold
The submaximal exercise test protocol (a ramp load 10 W·min-1) was used to determine the AT
O2 of all subjects. An electrocardiographic signal (CM5) was monitored during the whole experimental session. The ventilation volume, oxygen uptake, and carbon dioxide production were measured using an open system Aero-monitor AE 280 (Minato Medical Science, Osaka, Japan). The anaerobic threshold (18) was determined by submaximal exercise testing accomplished by cycle ergometer. The exercise test was terminated for the safety of our elderly subjects once AT
O2 was clearly identified. All AT
O2 determinations were performed by the same investigator, who was blinded to the assignment of the fitness category of the subjects. Our computer-aided gas exchange parameters and AT
O2 determination procedures have been previously reported elsewhere (19)(20).
ECG and BP Recordings at Rest and During the Tilt
All subjects received bipolar lead (CM5 lead) ECG for 256 s after the stabilization period. Simultaneously, the indirect BP wave was recorded using an automatic sphygnomanometer (Finapress 2300, Ohmeda, Englewood, CO) connected to a finger cuff containing a plethysmotranducer. The finger cuff was fitted to the middle finger of the left hand, while the forearm and the hand were maintained horizontal, at the level of the fifth intercostal space with the aid of a support. Then, analog output of the electrocardiogram (ECG) (with band pass filter between 0.5 and 100 Hz) and BP signal were digitized via a 13-bit analog-to-digital converter (Trans Era A/D 410, South Orem, UT) at a sampling rate of 1 kHz. The ECG and BP signals were simultaneously stored on a computer hard disk for later analysis. Subjects were evaluated in the supine position on the tilt table and were instructed to relax and breathe in synchrony with a metronome at 15 times·min-1 (0.25 Hz). After at least a 10-minute stabilization period, resting cardiac autonomic functions and BRS data were then collected for 360 s including 270 s in rest and 90 s for head-up and head-down tilting. The baseline BP and HRV power spectral data were obtained during the supine resting condition for an initial period of 240 s. The BP signal was processed to detect beat-by-beat SBP and diastolic blood pressure (DBP) values and was then averaged for the entire 240-s period.
ECG R-R Interval Analysis
From the obtained ECG data, the QRS spikes and the interval of impulses (R-R intervals) were detected and sequentially aligned into 2-Hz time series (21) by means of our software. Then, the DC component and linear trend were completely removed by digital filtering for band-pass between 0.03 and 0.5 Hz. After passing through the Hamming-type data window, power spectral analysis by means of a fast Fourier transform was performed on consecutive 256-s time series of ECG R-R interval data obtained during rest.
The technique of ECG R-R power spectral analysis in our laboratory has been applied in physiological and clinical research fields, and its validity has been described in our previous studies (22)(23)(24). In brief, the technique of power spectral analysis of HRV provides a convenient and noninvasive way to derive specific quantitative information about the balance between parasympathetic nervous system and sympathetic nervous system influences on HR regulation (25)(26). To evaluate ANS activity, we analyzed low frequency (0.030.15 Hz, LO), high vagal component (0.150.5 Hz, HI), and total power (0.030.5 Hz, TOTAL) by integrating the spectrum of the respective bandwidth. The mean HR of each 256-s segment was also calculated together with standard deviation.
Postural Tilt Test
The subject was tilted head-up using a tilt table with straps around the upper parts of the chest, thighs, and ankles with his feet on a bottom plate. After supine rest, the tilt table was inclined in a 30-s period to 60° head-up-tilt (HUT) and maintained at this angle for 30 s. A tilt-back maneuver to the horizontal position was then performed during 30 s. None of the subjects developed symptoms of syncope during the tilt or upright position. The assessment of BRS was performed using simultaneous beat-by-beat SBP and ECG R-R interval measurements. Specifically, we assessed BRS by examining the magnitude of the ECG R-R interval per mm Hg change in SBP (
R-R/
SBP) during a transition from supine horizontal position to 60° HUT. Then, the consecutive changes in SBP and the corresponding ECG R-R interval were taken for analysis. Linear regression analyses of instantaneous changes in ECG R-R against SBP during tilting were calculated for each subject using our computer system. The fall in the SBP during the HUT caused a progressive shortening of the ECG R-R interval in all subjects. In our results, the fit of linear regression coefficient was on average r = .80 ± .12. The BRS during tilting was expressed as slope (gain) of regression equation derived from ECG R-R interval against the SBP.
Statistical Analysis
Data are expressed as mean values ± SE. A Student's unpaired t test was performed to assess statistical differences in anthropometrical characteristics and parameters regarding ANS and BRS between the two groups. An alpha level of .05 was used to determine statistical significance.
| Results |
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O2 ranged from 16.8 to 29.3 ml·kg-1·min-1. The mean AT
O2 of the physically fit (PF, 25.2 ± 0.85 ml·kg-1·min-1) group was significantly higher ( p = .001) than the physically unfit (PU, 19.6 ± 0.42 ml·kg-1·min-1) group. Furthermore, the questionnaire of history of physical activity revealed that the PF group had a mean of 10 (SE = 4.5), and the PU group had a mean of 1.7 (SE = 0.98), years of consecutive participation in exercise programs.
Spectral Analysis
Fig. 1 shows representative data sets using our analysis procedures. The overall R-R interval fluctuation in the PU group was much smaller compared with the PF group. Similarly, the HI and TOTAL powers were much reduced in the PU subjects than in the PF subjects. Fig. 2 represents the group data with respect to ECG R-R spectral parameters (LO, HI, and TOTAL) obtained from PF and PU groups during resting. The mean values of TOTAL powers (409 ± 110 vs 145 ± 39 ms2, p = .04) and HI frequency (141 ± 40 vs 41 ± 9 ms2, p = .03) were significantly higher in PF group. There was, however, no significant difference in LO frequency (269 ± 99 vs 104 ± 30 ms2, p = .14) between the PF and PU groups.
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O2 and BRS among the subjects. Fig. 5 represents a scatter plot between these variables.
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| Discussion |
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Because a significant alteration in ANS activities occurs with advancing age (16)(27) with the vagal predominance being significantly impaired (1), we compared the resting ANS activities using frequency domain spectral analyses in our PF and PU groups. In the resting conditions, we found a higher HRV together with significantly higher TOTAL (overall ANS activity) and HI (mainly PNS activity) frequency components in the PF group. During the HUT, our results showed that the PF older adults demonstrated a larger increase in HR with passive HUT as well as a smaller blood pressure fall as compared with PU older adult peers. Furthermore, we found a significant correlation (r = .73, p = .01) between AT
O2 and BRS in the 24 older adults evaluated. These results supported the earlier work of Frederiks and colleagues (28) using HUT to measure the BRS, demonstrating that the interruption of training resulted in a significant decrease in the
O2max in athletes, which correlated significantly (r = .71, p = .02) with the extent of decrease in BRS.
On the other hand, some investigators have reported that endurance exercise training may not be beneficial for highly fit endurance-trained individuals or athletes because they showed a deficient BRS during HUT and lower body negative pressure (29). It has been argued by Levine and colleagues (30) who reported that the elevated calf venous conductance as well as larger stroke volume in endurance athletes would be associated with a larger reduction in central blood volume during HUT, predisposing to blood pressure dysregulation. Furthermore, previous studies (31)(32) using spontaneous BRS and lower body negative pressure procedures in middle-aged and older women and men reported no alteration of BRS with moderate or strenuous exercise training for 12 and 30 weeks, respectively. It was suggested that more intense and prolonged training might be required to bring about significant changes in BRS. In the absence of significant alterations in cardiac PNS activity, one of the major factors controlling BRS, it may be difficult to alter BRS to a significant extent. Thus, so far, the evidence for altered BRS following exercise training has been remarkably inconsistent due possibly to the selection of subjects, age, gender, training intensity, duration, and the subject trainability as well as the methods of BRS determination.
Some studies have demonstrated that the amplitude of HRV at rest conditions was correlated with BRS. Cardiac vagal activity was also found to increase as a sigmoid function in proportion to the intensity of baroreceptor stimulation (33). O'Leary and Seamans (34) reported that a reflex change in HR was dependent on the relative tonic level of autonomic nervous activities. Recently, Kollai and colleagues (15) estimated the relation between cardiac vagal tone and BRS using regression between cardiac vagal tone against BRS in response to cholinergic blockade. They reported that cardiac vagal tone could be generated by both baroreflex-dependent (69%) and independent mechanisms (1622%), while the baroreflex-dependent mechanism was the dominant factor. The results of our study showed a higher cardiac vagal tone (HI frequency) as well as markedly higher BRS in the PF group compared with less fit older adults. These results support the previous investigation (35) and reinforce that one mechanism of enhanced baroreflex response among physically fit individuals might be related to an enhanced cardiac responsiveness to vagal input. This notion was substantiated by our finding of a significantly larger increase in delta HR during the HUT, which could in turn counteract against the rapid fall in SBP. Because our PF group showed lower HR than the PU group before the tilting (although the difference was not statistically significant), one might think that the significant increase in HR observed for PF disappears if the HR were to be equated. This was, however, not the case because lower HR with larger stroke volume would require a smaller HR increase for adjusting BP for any given changes. The significantly larger increase in HR was, therefore, at least in part, a result of well-preserved cardiac PNS responsiveness.
Another speculative mechanism by which an increase in cardiovascular fitness is associated with enhancement of BRS in older adults is that endurance training but not recreational activity results in increased arterial compliance (36). The stiffening of large cardiothoracic arteries might lead to less afferent firing for a given change in arterial pressure, which would reduce baroreceptor afferent responsiveness (37). Thus, this modification in vessel wall properties can contribute to the age-related impairments in BRS, which reduce the capacity of normal elderly persons to increase the HR in response to hypotensive stress and contribute to the increased prevalence of orthostatic hypotension with advancing age (38).
This study suggests that older adults with higher levels of cardiorespiratory fitness induced adaptations in the cardiac autonomic functions as well as BRS. Whereas, the maintenance of higher levels of cardiorespiratory fitness together with higher parasympathetic predominance may attenuate age-related neural and vessel wall properties and mechanical changes in the heart that lead to a decrease in BRS. These adaptations may be a cardioprotective factor that contributes to increase the fibrillation threshold as well as greater BP buffering action, including those caused by postural changes, which requires a major demand of the neural system to keep the homeostasis in older adults.
| Acknowledgments |
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Received January 2, 2002
Accepted April 9, 2002
| References |
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O2max. Aviat Space Environ Med. 55:702-708. [Medline]
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