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Changes of autonomic nervous system function in healthy young men during initial phase at acute high-altitude exposure
आऋऑऎऊࣽईࣜऋंࣜ उँऀअࣿࣽईࣜ ࣿऋईईँःँएࣜऋंࣜऌईࣽ Journal of Medical Colleges of PLA 23 (2008) 270–275
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Changes of autonomic nervous system function in healthy young men during initial phase at acute high-altitude exposure Qin Jun1, Huang Lan1, Tian Kaixin1, Yu Shiyong1, Yu Yang1, Long Min2* 1
Cardiovascular Diseases Research Center, Xinqiao Hospital, Third military medical university, Chongqing 400037, China 2 Department of Endocrinology, Xinqiao Hospital, Third military medical university, Chongqing 400037, China Received 25 January 2008; accepted 28 April 2008
Abstract Objective: To investigate the changes of autonomic nervous system (ANS) function during the initial phase at acute high-altitude exposure. Methods: Ninety-nine healthy sea-level male residents were studied in Chengdu plain and then Tibet plateau. Heart rate variability (HRV), cold pressor test (CPT), resting heart rate (HR) and blood pressure (BP) were measured at baseline (560 m altitude) and in 2 to 4 d after arriving at Tibet plateau (3 675 m altitude) to assess the ANS function. Results: Compared with baseline, on day 2 in Tibet the standard deviation of normal to normal intervals (SDNN), high-frequency (HF) power, total power (TP), root mean square of delta RR (rMSSD), percentage of delta RR>50 ms (PNN 50 ), normalized high-frequency (HFnu) and fractal dimension (FD) decreased significantly (SDNN, HF, TP P<0.01, rMSSD, PNN 50 , HFnu, FD P<0.05), while the normalized low-frequency (LFnu) and LF/HF increased significantly (P<0.01). During day 3–4 in Tibet, SDNN, rMSSD, HF, TP and HFnu tended to rebound while LFnu and LF/HF decreased towards baseline day by day. In addition, in Tibet the increase in systolic pressure (SP) and diastolic pressure (DP) during CPT decreased significantly (P<0.01, 0.05), but resting HR increased compared with baseline (P<0.01). Conclusion: ANS modulation is generally blunted, and the relatively predominant sympathetic control is enhanced originally, then it reverts to the sea level states gradually during the initial days of acute high-altitude exposure. Keywords: Autonomic nervous system; High altitude; Heart rate variability; Cold pressor test
1. Introduction Acute mountain sickness (AMS) is very * Corresponding author. Tel.: 86-23-68774601 E-mail address: [email protected] (Long M.)
common in people who ascend from sea level to altitudes higher than approximate 3 000 m. We have known typical symptoms begin after 2–3 h exposure to acute high altitude, and then the symptoms will aggravate gradually. In 2–3 days later, AMS will be greatly alleviated [1]. Since AMS usually occurs in the first several days of
Qin Jun et al. / Journal of Medical Colleges of PLA 23 (2008) 270–275
acute high altitude exposure, we define it as the initial phase of acute high altitude exposure. The pathogenesis of AMS is not quite clear up to now. Recently, several studies revealed autonomic nervous system (ANS) was involved in AMS [2–4], and rough change of sympathetic and parasympathetic activity had been indicated [5–8]. However, so far few field studies about the change of ANS function have been carried out during the initial phase of acute high-altitude exposure due to the practical difficulty in plateau field study. In addition, the conclusions are inconsistent [5, 9, 10]. In our study, we attempted to reveal the dynamic change of ANS function during the initial phase of acute high-altitude exposure, and hope to provide practical evidences to AMS pathogenesis.
2. Subjects and methods
2.1. Subjects and procedure Ninety-nine healthy, nonsmoking sea-level male residents (age 19.20±0.96, height 167.00± 3.33 cm, body weight 59.16±5.63 kg) were subjected in this study. All subjects were recruited after being interviewed with a standardized scheme to ascertain their medical history. None of them suffered from any cardiovascular or pulmonary disease. Records were obtained at 560 m altitude (Chengdu plain, Sichuan province, China) and on day 2–4 at 3 675 m altitude (Tibet plateau, Tibet autonomous region, China). All subjects were transported by airplane to the Tibet plateau within 90 min. In the study, temperature was kept constant at 14–20 ć. Subjects were banned to drink coffee or take any medicine. Before each measurement, a 15-minute rest was necessary.
2.2. Heart rate variability (HRV) Analysis of HRV is an effective, noninvasive
271
method of assessing the cardiocirculatory system control, because it enables a distinction between sympathetic and parasympathetic components of the ANS. Owing to technique failure, 13 subjects HRV initial data were lost. After completed 5 min R-R intervals recording (Model D/SF-ĉ, Dikang Medical Digital Instru- ment Co. Ltd, Chengdu, China) in Chengdu plain successfully, 86 subjects were randomly assigned to group A (n=12), group B (n=48) and group C (n=26). They had no obvious difference in HRV at 560 m altitude. After exposure to plateau, group A received HRV testing on the 2nd day, group B was measured on the 3rd day, and group C did on the 4th day. Standard deviation of normal to normal intervals (SDNN), one important time domain index, reflects all the cyclic components responsible for variability in the period of recording. Root mean square of delta RR (rMSSD) and percentage of delta RR>50 ms (PNN 50) were closely related to parasympathetic activity. Power spectrum was obtained by an autoregressive modeling technique. The total power (TP, 0.03–0.15 Hz) is used to estimate of overall autonomic nervous activity. Disagreement exists in respect to the low-frequency (LF) power (0.04– 0.15 Hz), most of studies regard LF power as reflecting both sympathetic activity and parasympathetic activity. High-frequency (HF) power (0.15–0.40 Hz) is regarded as a marker of tonic parasympathetic activity. The representation of LF power and HF power in normalized units (LFnu=LF/[TPíVLF]×100%,HFnu=HF/[TPíVLF] ×100%, VLF refers to very low-frequency power) emphasizes the controlled and balanced behavior of the two branches of the autonomic nervous system. The LF-to-HF ratio (LF/HF) is considered by some investigators to mirror sympathovagal balance or to reflect the sympathetic modulations. Fractal dimension (FD), the only non-linear parameter in this study, reflects complex physiological meaning and related to autonomic and central nervous regulations [11].
272
Qin Jun et al. / Journal of Medical Colleges of PLA 23 (2008) 270–275
electrocardiogram monitor in plain and on day 2 in plateau.
2.3. Cold pressor test (CPT) Because of severe complaints during test and technique failure, 72 subjects’ CPT was performed in Chengdu plain and on day 2 in Tibet plateau respectively. After subjects had rested upright for at least 15 min indoor, resting blood pressure (BP) was measured in the right upper arm with an electrocardiogram monitor (MP-900F, Nanning Sanqiu Commerce Trade Co, Ltd, Nanning, China). The left hand below wrist was then immersed in cold water (3 to 5 ć ) for 2 min; blood pressure measurements were obtained at 30, 120, and 300 s after immersion. The maximal changes in systolic pressure (SP) and diastolic pressure (DP) from resting values during cold stimulus were defined as systolic response and diastolic response respecttively.
2.4. Resting blood pressure (BP) and heart rate(HR) In early morning, resting BP and HR were measured at the right brachial artery with an
2.5. Statistical analysis Data were analyzed with SPSS (Version 10.0) statistical package. Results were expressed as means±SD. Comparisons of different groups’ HRV means were analyzed by one-way analysis of variance (ANOVA). Comparison between sets was conducted by Q-test. The level of statistical significance was set at 0.05.
3. Results 3.1. Results of HRV Table 1 shows the dynamic change of HRV in the initial phase of acute exposure to Tibet plateau in detail. SDNN, HF power and TP were decreased significantly on day 2 in Tibet plateau compared with baseline (P<0.01). rMSSD, PNN50, HFnu and FD also were reduced obviously (P<0.05). Similarly LF power had a tendency to decrease (P>0.05). But both LFnu and LF/HF ratio were
Table 1 Dynamic change of HRV in initial phase of acute exposure to Tibet plateau (mean±SD) Parameters SDNN (ms)
Chengdu plain
On day 2 in Tibet
On day 3 in Tibet
On day 4 in Tibet
(n=86)
plateau (n=12)
plateau (n=48)
plateau (n=26)
62.81±35.51
40.26±17.59
b a
rMSSD (ms)
70.33±51.19
41.06±27.54
PNN 50 (%)
15.55±9.46
8.22±7.80 a
LF power (ms2 ) 2
HF power (ms ) 2
TP (ms )
156.02±140.17 205.92±226.42 497.45±409.07
105.45±78.92 73.95±63.19
b
260.31±195.41 b
b
45.58±23.13
b
52.36±37.29
47.46±31.34
a
57.83±58.63
10.46±10.03 b
6.43±6.17 a
101.80±74.09 b
115.95±83.23
98.08±88.47 b
110.62±109.91
340.59±220.92
374.34±310.22
48.87±16.51
a
49.11±15.28
LFnu (%)
42.66±11.80
56.44±15.13
HFnu (%)
51.92±12.72
40.74±14.16 a
44.08±15.10 b
45.39±15.02 a
0.93±0.52
1.92±1.46 b
1.36±1.02 a
1.31±0.80 a
6.93±1.39
a
a
5.55±1.85 a
LF/HF ratio FD
5.61±2.44
6.08±1.28
SDNN: standard deviation of normal to normal intervals; rMSSD: root mean square of delta RR; PNN50 : percentage of delta RR>50 ms; LF: low-frequency; HF: high-frequency; TP: total power; LFnu: LF/TPíVLF×100%; HFnu: HF/TPíVLF×100%; FD: fractal dimension; aP<0.05, b P<0.01vs baseline (Chengdu plain).
Qin Jun et al. / Journal of Medical Colleges of PLA 23 (2008) 270–275
increased significantly (P<0.01). From day 3 to day 4 SDNN, rMSSD, HF, TP, HFnu and LF tended to rebound, while LFnu and LF/HF ratio presented an opposite change. In addition PNN50 and FD undulated at the low level. On day 4, HFnu, PNN50 and FD were significantly lower than baseline (P<0.05), while LF/HF was significantly higher (P<0.05).
3.2. Outcomes of CPT Compared with baseline, the increase in SP and DP during CPT displayed a more pronounced decline (SP: 17.05±10.91 vs 10.76±8.42 mmHg, P<0.01; DP: 13.20±8.70 vs 9.86±6.43 mmHg, P<0.05). While resting HR increased significantly at acute exposure to Tibet plateau (75.07±12.16 vs 96.42±13.54 bpm, P<0.01). No marked change was found in resting SP and DP (SP:120.49±11.65 vs 119.35±12.91 mmHg, P>0.05; DP: 80.05±7.80 vs 80.49±9.59 mmHg, P>0.05).
4. Discussion Since 1990s, a few studies on the change of ANS function at acute high-altitude exposure have been carried out. Most of them indicated hypoxia caused decreased parasympathetic and increased sympathetic activity [9, 12, 13]. However, ANS measurements in most previous studies were finished on day 5 or even after a week at high altitude. Not only the measurements were late, but also only a small scale of subjects (usually less than 10) was involved. At present, accurate dynamic change of ANS activity in the initial several days of acute high-altitude exposure was not very clear and the change in ANS modulation awaited an in-depth study. In the present study, dynamic analysis of HRV parameters on day 2–4 showed that SDNN, rMSSD, HF, TP and HFnu decreased significantly on day 2 in Tibet plateau but tended to increase on day 3–4. While LFnu and LF/HF increased significantly on
273
day 2 in Tibet plateau and tended to decrease on day 3–4. PNN 50, HFnu, LF/HF and FD on day 4 in Tibet plateau were still significantly different from the baseline. Dynamic changes of HRV indicated that ANS modulation and parasympathetic activity tended to recover day by day after a transient reduction. The balance of sympathetic and parasympathetic nervous turned to relatively predominant sympathetic control at acute exposure to Tibet plateau initially, then tended to recover to baseline state. In addition we have to notice that not every subject’s HRV was recorded daily at high altitude. In order to exclude the internal difference among groups, we designed three groups which had similar HRV in plain. CPT is a classic method of assessing sympathetic modulation through nervous reflex. Body’s reaction to the stress reflects ANS modulation. Overreaction in CPT (BP is elevated over 20/20 mmHg) suggests that the sympathetic activity is too active [14], for ANS modulation on cardiovascular system is relatively weak [15].The increase in SP and DP during CPT in the initial phase of acute exposure to Tibet plateau decreased, which suggested sympathetic activity decreased and ANS modulating function reduced. This finding was in agreement with the HRV results of this study and our previous study [8]. Similarly, in a study about stepwise exposure of 12 young males to a simulated altitude of 4 500 m, researchers have found that increase in SP during CPT decreased significantly compared with baseline [6]. In addition, the attenuate of sympathetic activity and ANS modulation also were confirmed by decrease of plasma neurotransmitter noradrenaline (NA) secreted by sympathetic nervous system and BP in mental stress test in the initial phase of acute high-altitude exposure [6]. The reports on resting HR and BP change at acute high-altitude exposure were different from one another. Except for significant change of HRV and total peripheral resistances, a field study found that SP, DP and HR on day 2 and day 6 at 4 350 m
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altitude were significantly higher than the baseline [5]. Researchers concluded that this kind of BP change was related to increased sympathetic activity [5]. Despite the significant increase in resting HR in the initial phase of acute exposure to Tibet plateau, marked change in resting SP and DP was not found in our study. The change of arterial blood pressure did not support increased sympathetic activity in the initial phase of acute high-altitude exposure. Compared with the heart controlled by ANS, HR of denervated human heart in heart transplanted subjects increased significantly for lack of ANS control [16]. In our study, the generally reduced ANS activity and significantly increased HR were found, which were similar to those of denervated heart. We had to suppose HR and BP change in the initial phase of acute high-altitude exposure were probably related to the generally reduced ANS activity and the rebuilt balance between sympathetic and parasympathetic nervous systems. We held that in assessing ANS function, 3 aspects should be kept in mind: (1) absolute activities of sympathetic and parasympathetic; (2) the balance between sympathetic and parasympathetic; (3) ANS modulation in response to stress. The above three aspects, jointly reflecting ANS function, were to be considered together in the assessment of ANS function in our study. In summary, sympathetic and parasympathetic activities reduced transiently, sympathetic control was predominant, and ANS modulation was generally blunted, during initial phase at acute high-altitude exposure. Then, ANS function subsequently recovered to the baseline state gradually. It should be noted that owing to the limitation of the conditions in our present study, ANS function was not monitored on day 1 in Tibet plateau. Basing on HRV change on day 2–4, we inferred that the reduction of ANS modulation was more noticeable on day 1 at acute high-altitude exposure than on day 2.
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www.elsevier.com/locate/jmcpla
Changes of autonomic nervous system function in healthy young men during initial phase at acute high-altitude exposure Qin Jun1, Huang Lan1, Tian Kaixin1, Yu Shiyong1, Yu Yang1, Long Min2* 1
Cardiovascular Diseases Research Center, Xinqiao Hospital, Third military medical university, Chongqing 400037, China 2 Department of Endocrinology, Xinqiao Hospital, Third military medical university, Chongqing 400037, China Received 25 January 2008; accepted 28 April 2008
Abstract Objective: To investigate the changes of autonomic nervous system (ANS) function during the initial phase at acute high-altitude exposure. Methods: Ninety-nine healthy sea-level male residents were studied in Chengdu plain and then Tibet plateau. Heart rate variability (HRV), cold pressor test (CPT), resting heart rate (HR) and blood pressure (BP) were measured at baseline (560 m altitude) and in 2 to 4 d after arriving at Tibet plateau (3 675 m altitude) to assess the ANS function. Results: Compared with baseline, on day 2 in Tibet the standard deviation of normal to normal intervals (SDNN), high-frequency (HF) power, total power (TP), root mean square of delta RR (rMSSD), percentage of delta RR>50 ms (PNN 50 ), normalized high-frequency (HFnu) and fractal dimension (FD) decreased significantly (SDNN, HF, TP P<0.01, rMSSD, PNN 50 , HFnu, FD P<0.05), while the normalized low-frequency (LFnu) and LF/HF increased significantly (P<0.01). During day 3–4 in Tibet, SDNN, rMSSD, HF, TP and HFnu tended to rebound while LFnu and LF/HF decreased towards baseline day by day. In addition, in Tibet the increase in systolic pressure (SP) and diastolic pressure (DP) during CPT decreased significantly (P<0.01, 0.05), but resting HR increased compared with baseline (P<0.01). Conclusion: ANS modulation is generally blunted, and the relatively predominant sympathetic control is enhanced originally, then it reverts to the sea level states gradually during the initial days of acute high-altitude exposure. Keywords: Autonomic nervous system; High altitude; Heart rate variability; Cold pressor test
1. Introduction Acute mountain sickness (AMS) is very * Corresponding author. Tel.: 86-23-68774601 E-mail address: [email protected] (Long M.)
common in people who ascend from sea level to altitudes higher than approximate 3 000 m. We have known typical symptoms begin after 2–3 h exposure to acute high altitude, and then the symptoms will aggravate gradually. In 2–3 days later, AMS will be greatly alleviated [1]. Since AMS usually occurs in the first several days of
Qin Jun et al. / Journal of Medical Colleges of PLA 23 (2008) 270–275
acute high altitude exposure, we define it as the initial phase of acute high altitude exposure. The pathogenesis of AMS is not quite clear up to now. Recently, several studies revealed autonomic nervous system (ANS) was involved in AMS [2–4], and rough change of sympathetic and parasympathetic activity had been indicated [5–8]. However, so far few field studies about the change of ANS function have been carried out during the initial phase of acute high-altitude exposure due to the practical difficulty in plateau field study. In addition, the conclusions are inconsistent [5, 9, 10]. In our study, we attempted to reveal the dynamic change of ANS function during the initial phase of acute high-altitude exposure, and hope to provide practical evidences to AMS pathogenesis.
2. Subjects and methods
2.1. Subjects and procedure Ninety-nine healthy, nonsmoking sea-level male residents (age 19.20±0.96, height 167.00± 3.33 cm, body weight 59.16±5.63 kg) were subjected in this study. All subjects were recruited after being interviewed with a standardized scheme to ascertain their medical history. None of them suffered from any cardiovascular or pulmonary disease. Records were obtained at 560 m altitude (Chengdu plain, Sichuan province, China) and on day 2–4 at 3 675 m altitude (Tibet plateau, Tibet autonomous region, China). All subjects were transported by airplane to the Tibet plateau within 90 min. In the study, temperature was kept constant at 14–20 ć. Subjects were banned to drink coffee or take any medicine. Before each measurement, a 15-minute rest was necessary.
2.2. Heart rate variability (HRV) Analysis of HRV is an effective, noninvasive
271
method of assessing the cardiocirculatory system control, because it enables a distinction between sympathetic and parasympathetic components of the ANS. Owing to technique failure, 13 subjects HRV initial data were lost. After completed 5 min R-R intervals recording (Model D/SF-ĉ, Dikang Medical Digital Instru- ment Co. Ltd, Chengdu, China) in Chengdu plain successfully, 86 subjects were randomly assigned to group A (n=12), group B (n=48) and group C (n=26). They had no obvious difference in HRV at 560 m altitude. After exposure to plateau, group A received HRV testing on the 2nd day, group B was measured on the 3rd day, and group C did on the 4th day. Standard deviation of normal to normal intervals (SDNN), one important time domain index, reflects all the cyclic components responsible for variability in the period of recording. Root mean square of delta RR (rMSSD) and percentage of delta RR>50 ms (PNN 50) were closely related to parasympathetic activity. Power spectrum was obtained by an autoregressive modeling technique. The total power (TP, 0.03–0.15 Hz) is used to estimate of overall autonomic nervous activity. Disagreement exists in respect to the low-frequency (LF) power (0.04– 0.15 Hz), most of studies regard LF power as reflecting both sympathetic activity and parasympathetic activity. High-frequency (HF) power (0.15–0.40 Hz) is regarded as a marker of tonic parasympathetic activity. The representation of LF power and HF power in normalized units (LFnu=LF/[TPíVLF]×100%,HFnu=HF/[TPíVLF] ×100%, VLF refers to very low-frequency power) emphasizes the controlled and balanced behavior of the two branches of the autonomic nervous system. The LF-to-HF ratio (LF/HF) is considered by some investigators to mirror sympathovagal balance or to reflect the sympathetic modulations. Fractal dimension (FD), the only non-linear parameter in this study, reflects complex physiological meaning and related to autonomic and central nervous regulations [11].
272
Qin Jun et al. / Journal of Medical Colleges of PLA 23 (2008) 270–275
electrocardiogram monitor in plain and on day 2 in plateau.
2.3. Cold pressor test (CPT) Because of severe complaints during test and technique failure, 72 subjects’ CPT was performed in Chengdu plain and on day 2 in Tibet plateau respectively. After subjects had rested upright for at least 15 min indoor, resting blood pressure (BP) was measured in the right upper arm with an electrocardiogram monitor (MP-900F, Nanning Sanqiu Commerce Trade Co, Ltd, Nanning, China). The left hand below wrist was then immersed in cold water (3 to 5 ć ) for 2 min; blood pressure measurements were obtained at 30, 120, and 300 s after immersion. The maximal changes in systolic pressure (SP) and diastolic pressure (DP) from resting values during cold stimulus were defined as systolic response and diastolic response respecttively.
2.4. Resting blood pressure (BP) and heart rate(HR) In early morning, resting BP and HR were measured at the right brachial artery with an
2.5. Statistical analysis Data were analyzed with SPSS (Version 10.0) statistical package. Results were expressed as means±SD. Comparisons of different groups’ HRV means were analyzed by one-way analysis of variance (ANOVA). Comparison between sets was conducted by Q-test. The level of statistical significance was set at 0.05.
3. Results 3.1. Results of HRV Table 1 shows the dynamic change of HRV in the initial phase of acute exposure to Tibet plateau in detail. SDNN, HF power and TP were decreased significantly on day 2 in Tibet plateau compared with baseline (P<0.01). rMSSD, PNN50, HFnu and FD also were reduced obviously (P<0.05). Similarly LF power had a tendency to decrease (P>0.05). But both LFnu and LF/HF ratio were
Table 1 Dynamic change of HRV in initial phase of acute exposure to Tibet plateau (mean±SD) Parameters SDNN (ms)
Chengdu plain
On day 2 in Tibet
On day 3 in Tibet
On day 4 in Tibet
(n=86)
plateau (n=12)
plateau (n=48)
plateau (n=26)
62.81±35.51
40.26±17.59
b a
rMSSD (ms)
70.33±51.19
41.06±27.54
PNN 50 (%)
15.55±9.46
8.22±7.80 a
LF power (ms2 ) 2
HF power (ms ) 2
TP (ms )
156.02±140.17 205.92±226.42 497.45±409.07
105.45±78.92 73.95±63.19
b
260.31±195.41 b
b
45.58±23.13
b
52.36±37.29
47.46±31.34
a
57.83±58.63
10.46±10.03 b
6.43±6.17 a
101.80±74.09 b
115.95±83.23
98.08±88.47 b
110.62±109.91
340.59±220.92
374.34±310.22
48.87±16.51
a
49.11±15.28
LFnu (%)
42.66±11.80
56.44±15.13
HFnu (%)
51.92±12.72
40.74±14.16 a
44.08±15.10 b
45.39±15.02 a
0.93±0.52
1.92±1.46 b
1.36±1.02 a
1.31±0.80 a
6.93±1.39
a
a
5.55±1.85 a
LF/HF ratio FD
5.61±2.44
6.08±1.28
SDNN: standard deviation of normal to normal intervals; rMSSD: root mean square of delta RR; PNN50 : percentage of delta RR>50 ms; LF: low-frequency; HF: high-frequency; TP: total power; LFnu: LF/TPíVLF×100%; HFnu: HF/TPíVLF×100%; FD: fractal dimension; aP<0.05, b P<0.01vs baseline (Chengdu plain).
Qin Jun et al. / Journal of Medical Colleges of PLA 23 (2008) 270–275
increased significantly (P<0.01). From day 3 to day 4 SDNN, rMSSD, HF, TP, HFnu and LF tended to rebound, while LFnu and LF/HF ratio presented an opposite change. In addition PNN50 and FD undulated at the low level. On day 4, HFnu, PNN50 and FD were significantly lower than baseline (P<0.05), while LF/HF was significantly higher (P<0.05).
3.2. Outcomes of CPT Compared with baseline, the increase in SP and DP during CPT displayed a more pronounced decline (SP: 17.05±10.91 vs 10.76±8.42 mmHg, P<0.01; DP: 13.20±8.70 vs 9.86±6.43 mmHg, P<0.05). While resting HR increased significantly at acute exposure to Tibet plateau (75.07±12.16 vs 96.42±13.54 bpm, P<0.01). No marked change was found in resting SP and DP (SP:120.49±11.65 vs 119.35±12.91 mmHg, P>0.05; DP: 80.05±7.80 vs 80.49±9.59 mmHg, P>0.05).
4. Discussion Since 1990s, a few studies on the change of ANS function at acute high-altitude exposure have been carried out. Most of them indicated hypoxia caused decreased parasympathetic and increased sympathetic activity [9, 12, 13]. However, ANS measurements in most previous studies were finished on day 5 or even after a week at high altitude. Not only the measurements were late, but also only a small scale of subjects (usually less than 10) was involved. At present, accurate dynamic change of ANS activity in the initial several days of acute high-altitude exposure was not very clear and the change in ANS modulation awaited an in-depth study. In the present study, dynamic analysis of HRV parameters on day 2–4 showed that SDNN, rMSSD, HF, TP and HFnu decreased significantly on day 2 in Tibet plateau but tended to increase on day 3–4. While LFnu and LF/HF increased significantly on
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day 2 in Tibet plateau and tended to decrease on day 3–4. PNN 50, HFnu, LF/HF and FD on day 4 in Tibet plateau were still significantly different from the baseline. Dynamic changes of HRV indicated that ANS modulation and parasympathetic activity tended to recover day by day after a transient reduction. The balance of sympathetic and parasympathetic nervous turned to relatively predominant sympathetic control at acute exposure to Tibet plateau initially, then tended to recover to baseline state. In addition we have to notice that not every subject’s HRV was recorded daily at high altitude. In order to exclude the internal difference among groups, we designed three groups which had similar HRV in plain. CPT is a classic method of assessing sympathetic modulation through nervous reflex. Body’s reaction to the stress reflects ANS modulation. Overreaction in CPT (BP is elevated over 20/20 mmHg) suggests that the sympathetic activity is too active [14], for ANS modulation on cardiovascular system is relatively weak [15].The increase in SP and DP during CPT in the initial phase of acute exposure to Tibet plateau decreased, which suggested sympathetic activity decreased and ANS modulating function reduced. This finding was in agreement with the HRV results of this study and our previous study [8]. Similarly, in a study about stepwise exposure of 12 young males to a simulated altitude of 4 500 m, researchers have found that increase in SP during CPT decreased significantly compared with baseline [6]. In addition, the attenuate of sympathetic activity and ANS modulation also were confirmed by decrease of plasma neurotransmitter noradrenaline (NA) secreted by sympathetic nervous system and BP in mental stress test in the initial phase of acute high-altitude exposure [6]. The reports on resting HR and BP change at acute high-altitude exposure were different from one another. Except for significant change of HRV and total peripheral resistances, a field study found that SP, DP and HR on day 2 and day 6 at 4 350 m
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altitude were significantly higher than the baseline [5]. Researchers concluded that this kind of BP change was related to increased sympathetic activity [5]. Despite the significant increase in resting HR in the initial phase of acute exposure to Tibet plateau, marked change in resting SP and DP was not found in our study. The change of arterial blood pressure did not support increased sympathetic activity in the initial phase of acute high-altitude exposure. Compared with the heart controlled by ANS, HR of denervated human heart in heart transplanted subjects increased significantly for lack of ANS control [16]. In our study, the generally reduced ANS activity and significantly increased HR were found, which were similar to those of denervated heart. We had to suppose HR and BP change in the initial phase of acute high-altitude exposure were probably related to the generally reduced ANS activity and the rebuilt balance between sympathetic and parasympathetic nervous systems. We held that in assessing ANS function, 3 aspects should be kept in mind: (1) absolute activities of sympathetic and parasympathetic; (2) the balance between sympathetic and parasympathetic; (3) ANS modulation in response to stress. The above three aspects, jointly reflecting ANS function, were to be considered together in the assessment of ANS function in our study. In summary, sympathetic and parasympathetic activities reduced transiently, sympathetic control was predominant, and ANS modulation was generally blunted, during initial phase at acute high-altitude exposure. Then, ANS function subsequently recovered to the baseline state gradually. It should be noted that owing to the limitation of the conditions in our present study, ANS function was not monitored on day 1 in Tibet plateau. Basing on HRV change on day 2–4, we inferred that the reduction of ANS modulation was more noticeable on day 1 at acute high-altitude exposure than on day 2.
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