- Email: [email protected]
Muscle sympathetic nerve response to vestibular stimulation by sinusoidal linear acceleration in humans
Neuroscience Letters 267 (1999) 181±184
Muscle sympathetic nerve response to vestibular stimulation by sinusoidal linear acceleration in humans Jian Cui a, Satoshi Iwase a, Tadaaki Mano a,*, Naomi Katayama b, Shigeo Mori b a
Department of Autonomic Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464±8601, Japan b Space Medicine Research Center, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464±8601, Japan Received 14 January 1999; received in revised form 13 April 1999; accepted 13 April 1999
Abstract To clarify the effects of natural otolith stimulation on muscle sympathetic nerve activity (MSNA) in humans, eight male volunteers were seated in a linear accelerator (sled) during the recording of MSNA from the tibial nerve with microneurography, and also the recording of electrocardiogram, blood pressure measured with a Finapres device and thoracic impedance during movement. Sinusoidal linear acceleration with peak values of ^0.10, 0.15 and 0.20 Gx were applied to the sitting subjects in the anteroposterior direction. Both the total activity and the burst rate of MSNA decreased during the sinusoidal linear acceleration, whereas the average heart rate, thoracic impedance and mean arterial pressure did not change signi®cantly. These results suggest that moderate sinusoidal linear acceleration in the anteroposterior direction may suppress MSNA in humans. q 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Muscle sympathetic nerve activity; Otolith; Microneurography
The sympathetic out¯ow to muscles, which plays an important role in cardiovascular control, is mediated by a number of re¯ex mechanisms. Although some research has focused on the vestibulo-autonomic re¯ex [1,4,8±10,12,14± 18], human studies on the re¯ex controlling the sympathetic out¯ow to muscles have not provided enough data to elucidate the precise mechanism. In our previous studies, we showed that the muscle sympathetic nerve activity (MSNA) from the human tibial nerve is enhanced after caloric vestibular stimulation [2,7], whereas the skin sympathetic nerve activity is suppressed during the nystagmus evoked by the caloric vestibular stimulation [3]. These results suggest that the stimulation of the horizontal semicircular canal has effects on sympathetic out¯ows to muscle and skin in humans. Animal studies showed that the vestibular afferents were involved in blood pressure regulation during postural changes in cats [4]. Yates et al. [15] demonstrated that the neurons in the rostral ventrolateral medulla, which is a major source of excitatory input to sympathetic preganglionic neurons, received vestibular input which appeared to come mainly from otolith receptors in cats. In human studies, MSNA was reported to increase during * Corresponding author. Tel.: 181-52-789-3883; fax: 181-52789-5047. E-mail address: [email protected] (T. Mano)
sustained head-down neck ¯exion, which was considered to be in¯uenced by static input from otolith organs [9,12]. Since an animal study showed that the response patterns of sympathetic nerve activity were related to the direction of the stimulation on the otolith organs [17], we hypothesized that the MSNA response to stimulation of otolith organs in humans in the anteroposterior (naso-occipital or occipitonasal) direction may be different from that in the craniocaudal direction. Furthermore, much less is known about the MSNA response to dynamic acceleratory stimulation of otolith organs in humans. Since otolith organs sense linear acceleration and head orientation with respect to gravity, we used a linear accelerator to stimulate the vestibular organs, especially otolith organs, in sitting subjects in the anteroposterior direction. Following the standard acceleration nomenclature as presented by Glaister [5], the forward acceleration is de®ned as 1Gx, which tends to displace internal tissues such as eyeballs to the occipital direction (`eyeballs in'); while the backward acceleration is de®ned as 2Gx, which tends to displace internal tissues to the nasal direction (`eyeballs out'). We recorded the MSNA from the tibial nerve with microneurography, and observed the hemodynamic responses during movement. Eight healthy male volunteers (mean age ^ SE, 21:8 ^ 0:4 years) participated in the present study. Written informed consent was obtained from each subject. The
0304-3940/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 9 9) 00 36 0- 2
182
J. Cui et al. / Neuroscience Letters 267 (1999) 181±184
Fig. 1. Representative tracings obtained for one subject during baseline, sinusoidal linear acceleration with peak value of ^0.10 Gx and after acceleration. The traces show the acceleration (Gx), instantaneous heart rate (HR), blood pressure (BP), and integrated muscle sympathetic nerve activity (MSNA).
study was approved by the Human Research Committee, Research Institute of Environmental Medicine, Nagoya University. Subjects were seated in a capsule of a linear accelerator (sled), in which a magnetic levitation system is employed at the Research Institute of Environmental Medicine, Nagoya University (Nagoya, Japan). The experimental capsule was sealed against electromagnetic noise and outside light. The subject was strapped into a chair of the capsule, and not only the body but also the head were ®rmly restrained with Velcro tape. The legs were extended at the knee joint in a horizontal position, and the feet were supported at the lower part of the calves with a supporter. Subjects were in a dark environment in the capsule during the experiments. Acceleration in a sinusoidal mode was applied along the anteroposterior (^Gx, naso-occipital and occipito-nasal) directions of subjects with a ®xed moving distance of 14
Table 1 The averages of burst rate and total activity of MSNA, heart rate (HR), thoracic impedance (Impedance), and mean arterial pressure (MAP) before, during and after sinusoidal linear acceleration a Baseline
Acc
MSNA (bursts/min) 23.6 ^ 1.4 13.4 ^ 1.3* MSNA (%) 100 60.1 ^ 5.0* HR (beats/min) 64.6 ^ 1.2 64.3 ^ 1.4 Impedance (V ) 29.1 ^ 0.4 29.2 ^ 0.5 MAP (mmHg) 99.8 ^ 2.2 100.4 ^ 2.3 a
After 1
n
19.0 ^ 1.8 86.4 ^ 9.8 65.3 ^ 1.3 29.1 ^ 0.4 99.5 ^ 2.1
4 4 8 8 8
The results are the averages of the three stimulations, in which the peak acceleration were at ^0.10, ^0.15, ^0.20 Gx. Values are means^SE. Baseline, 1 min before the movement; Acc, the total period of the sinusoidal linear acceleration; after 1, the ®rst minute after the movement stops. n, subject number. *P , 0:05 vs. baseline.
m. In each stimulation, ®ve cyclic movements with the same peak acceleration were repeated continuously. In each subject, three stimulations were applied, with peak values of the sinusoidal acceleration of ^0.10 Gx (0.98 m/s 2), ^0.15 Gx (1.47 m/s 2) and ^0.20 Gx (1.96 m/s 2), respectively. The periods for one cyclic movement with peak accelerations of ^0.10, 0.15 and 0.20 Gx were 16.7, 13.3 and 11.6 s, respectively. The interval between stimulations was 5 min. MSNA was recorded from the right tibial nerve by using microneurography in the same manner as in our previous studies [2,6,7,13]. After the signal was fed into an ampli®er (£50 000) and band-pass ®lters (500,5000 Hz), it was recti®ed and integrated in a resistance-capacitance network with a time constant of 0.1 s. The total activity of MSNA in the present experiments was de®ned as the `burst area' of the integrated neurogram over each second [13]. The ®nal values of total activity of MSNA were expressed in arbitrary units by setting the average value for 1 min before the movement as 100%. MSNA was also expressed as burst rate (burst number per minute). Heart rate was monitored by electrocardiography using a bioelectric ampli®er (AB621G, Nihon Kohden, Tokyo). The blood pressure waveform was recorded with a Finapres 2300 device (Ohmeda, Louisville, CO) on the subject's left or right middle ®nger, which was ®xed with adhesive tape at the level of the right atrium. The mean arterial pressure (MAP) was calculated as the sum of the diastolic blood pressure plus one-third of the pulse pressure in each beat. Subjects were asked to control their respiration rate at 0.25 Hz with a metronome. To estimate changes in intra-thoracic ¯uid volume, thoracic impedance (Zo) was measured with an impedance plethysmograph (AI-601G, Nihon Kohden, Tokyo) with electrodes taped circumferentially around the neck and the chest at the level of the xyphoid process. All signals were stored in a multichannel digital audio tape (DAT) recorder
J. Cui et al. / Neuroscience Letters 267 (1999) 181±184
Fig. 2. Changes in total activity of MSNA during sinusoidal linear acceleration with peak values of ^0.10, ^0.15 and ^0.20 Gx. The total activity of MSNA for the 1 min before the movement was used as the baseline (100%). The MSNA during the sinusoidal linear acceleration with the peak value of ^0.20 Gx was signi®cantly lower than that of ^0.10 Gx acceleration. Base, baseline; 0.10, 0.15, 0.20 Gx, the sinusoidal linear acceleration with peak values at ^0.10, ^0.15, ^0.20 Gx. Subject n 4. *P , 0:01 vs. baseline. #P , 0:005 vs. baseline.
(PC-216A, Sony Precision Technology, Tokyo). The average values of MAP, heart rate and thoracic impedance for 1 min just before the start of the movement served as baseline values. We applied one-way analysis of variance (ANOVA) to assess the changes of the parameters during and after acceleration. The blood pressure, heart rate and thoracic impedance were measured in all subjects. MSNA was recorded successfully in four subjects. Fig. 1 shows the heart rate, blood pressure waveform obtained with the Finapres device and integrated MSNA from the tibial nerve during sinusoidal linear acceleration with peak value of ^0.10 Gx in a representative subject. For the combined data of the three stimulations with the peak accelerations of ^0.10, ^0.15 and ^0.20 Gx, the burst rate and total activity of MSNA decreased signi®cantly compared with the baseline value during sinusoidal linear acceleration (Table 1). For the separate data of the three stimulations, the total activity of MSNA during sinusoidal linear acceleration was also significantly lower than the baseline activity (Fig. 2); while the total activity of MSNA during the sinusoidal linear acceleration with peak value of ^0.20 Gx was signi®cantly lower than that with the peak acceleration ^0.10 Gx (P , 0:05). After acceleration, the MSNA recovered to the baseline level in 1 min. During the sinusoidal linear acceleration, the average MAP, heart rate and thoracic impedance did not change signi®cantly compared to the baseline values for either the separate data or the combined data of the three (^0.10, ^0.15, ^0.20 Gx) stimulations (P . 0:05). There was no complaint of motion sickness symptoms such as nausea, dizziness or cold sweating in any of the subjects. The present data show that sinusoidal linear acceleration in the anteroposterior (naso-occipital and occipito-nasal) directions could suppress sympathetic out¯ow to muscle in sitting humans. This decrease in MSNA can be considered as a combined response to the sinusoidal linear accel-
183
eration, since the results were the average of data obtained when acceleration was in both directions. The decrease in the total activity of MSNA during sinusoidal linear acceleration showed a tendency to depend on the degree of acceleration up to 0.20 Gx. As the average MAP and average thoracic impedance did not change signi®cantly, the decrease in MSNA during sinusoidal linear acceleration could not be considered to be related to the arterial or cardiopulmonary barore¯exes. Since there is considerable evidence that stimulation of the vestibular system has effects on the activities of sympathetic preganglionic neurons in animals and of postganglionic nerves in animals and humans [2±5,7±10,12,14±18], the suppression of the MSNA during ^Gx acceleration in sitting subjects should be considered at least in part as a response evoked by the stimulation of the otolith organs. The decrease in MSNA observed in the present study is different from what was found in our previous studies, in which MSNA was increased during the caloric vestibular stimulation [2,7]. As the caloric vestibular stimulation has an effect on the unilateral semicircular canal and evokes motion sickness symptoms, the MSNA enhancement seen in previous experiments could be considered to be vestibulo-sympathetic responses related to motion sickness, caused partly by an imbalance between the bilateral semicircular canals. The linear acceleration in the present experiments stimulated bilateral otolith organs, and no motion sickness symptoms were observed. The MSNA decrease found in the present study can be considered to be a physiological response in sympathetic out¯ow to muscle during sinusoidal linear acceleration. Our ®nding of a decrease in MSNA in the present study is different from the signi®cant increase in MSNA found by Ray et al. [9] during sustained passive head-down neck ¯exion in the prone position in humans [9,12]. There are several differences in the protocols of the studies by Ray et al. and our study, which may have caused the differences in the results. First, the baseline positions of the subjects were different. The subjects were in a prone position in their studies, but a sitting position in our study. The baseline activity of the otolith organs should be different in these two conditions. Second, the directions of the stimulation were different. In the present experiments, the anteroposterior linear acceleration might mainly alter the utricular afferents [11]; whereas in the neck ¯exion posture, not only utricular afferents but also saccular afferents [11] would have been affected by the changes of the anteroposterior and craniocaudal component of the gravity of the otolith organs. Third, the intensities of the stimulation were different. The maximum change of acceleration in the present study was ^0.20 Gx, whereas the changes in both ^Gx and ^Gz of the otolith organs during the head-down neck ¯exion should have been stronger than those in our study. Fourth, the stimulation in the sinusoidal mode used in the present experiments might cause different responses from sustained stimulation. Therefore, the MSNA response during sinusoidal linear acceleration in the anteroposterior
184
J. Cui et al. / Neuroscience Letters 267 (1999) 181±184
direction might be different from that during head-down neck ¯exion. In conclusion, we observed that the MSNA was suppressed during the moderate sinusoidal linear acceleration in the anteroposterior direction in sitting human subjects. The present data provide useful information on sympathetic out¯ow to muscle in response to natural stimulation of otolith organs in humans. These ®ndings support the concept that otolith organs contribute to cardiovascular regulation in humans. [1] Costa, F., Lavin, P., Robertson, D. and Biaggioni, I., Effect of neurovestibular stimulation on autonomic regulation. Clin. Autonom. Res., 5 (1995) 289±293. [2] Cui, J., Mukai, C., Iwase, S., Sawasaki, N., Kitazawa, H., Mano, T., Sugiyama, Y. and Wada, Y., Response to vestibular stimulation of sympathetic out¯ow to muscle in humans. J. Auton. Nerv. Syst., 66 (1997) 154±162. [3] Cui, J., Iwase, S., Mano, T. and Kitazawa, H., Responses of sympathetic out¯ow to skin during caloric stimulation in humans. Am. J. Physiol., 276 (1999) R738±R744. [4] Doba, N. and Reis, D.J., Role of the cerebellum and vestibular apparatus in regulation of orthostatic re¯exes in the cat. Circ. Res., 34 (1974) 9±18. [5] Glaister, D.H., The effects of long duration acceleration. In J. Ernsting and P. King (Eds.), Aviation Medicine, Butterworths, London, 1988, p. 139. [6] Iwase, S., Mano, T., Watanabe, T., Saito, M. and Kobayashi, F., Age-related changes of sympathetic out¯ow to muscles in humans. J. Gerontol., 46 (1991) M1±M5. [7] Mano, T., Iwase, S., Saito, M., Koga, K., Abe, H., Inamura, K., Matsukawa, Y. and Hashiba, M., Somatosensory-vestibular -sympathetic interactions in man under weightlessness simulated by head-out water immersion. In J.C. Hwang (Ed.), Basic and Applied Aspects of Vestibular Function, Hong Kong University Press, Hong Kong, 1988, p. 193.
[8] Megirian, D. and Manning, J.W., Input-output relations in the vestibular system. Arch. Ital. Biol., 105 (1967) 151±164. [9] Ray, C.A. and Hume, K.M., Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic re¯ex. J. Appl. Physiol., 84 (1998) 450±453. [10] Ray, C.A., Hume, K.M. and Shortt, T.L., Skin sympathetic out¯ow during head-down neck ¯exion in humans. Am. J. Physiol., 273 (1997) R1142±R1146. [11] Schor, R.H. and Tomko, D.L., The vestibular system. In B.J. Yates and A.D. Miller (Eds.), Vestibular Autonomic Regulation, CRC Press, Boca Raton, FL, 1996, p. 7. [12] Shortt, T.L. and Ray, C., Sympathetic and vascular responses to head-down neck ¯exion in humans. Am. J. Physiol., 272 (1997) H1780±H1784. [13] Sugiyama, Y., Matsukawa, T., Suzuki, H., Iwase, S., Shamsuzzaman, A.S. and Mano, T., A new method of quantifying human muscle sympathetic nerve activity for frequency domain analysis. Electroenceph. clin. Neurophysiol., 101 (1996) 121±128. [14] Yates, B.J., Vestibular in¯uences on the sympathetic nervous system. Brain Res. Rev., 17 (1992) 51±59. [15] Yates, B.J., Goto, T. and Bolton, P.S., Responses of neurons in the rostral ventrolateral medulla of the cat to natural vestibular stimulation. Brain Res., 601 (1993) 255±264. [16] Yates, B.J., Grelot, L., Kerman, I.A., Balaban, C.D., Jakus, J. and Miller, A.D., Organization of vestibular inputs to nucleus tractus solitarius and adjacent structures in cat brain stem. Am. J. Physiol., 267 (1994) R974±R983. [17] Yates, B.J. and Millier, A.D., Properties of sympathetic re¯exes elicited by natural vestibular stimulation: implications for cardiovascular control. J. Neurophysiol., 71 (1994) 2087±2092. [18] Yates, B.J., Siniaia, M.S. and Miller, A.D., Descending pathways necessary for vestibular in¯uences on sympathetic and inspiratory out¯ow. Am. J. Physiol., 268 (1995) R1381±R1385.
Muscle sympathetic nerve response to vestibular stimulation by sinusoidal linear acceleration in humans Jian Cui a, Satoshi Iwase a, Tadaaki Mano a,*, Naomi Katayama b, Shigeo Mori b a
Department of Autonomic Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464±8601, Japan b Space Medicine Research Center, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464±8601, Japan Received 14 January 1999; received in revised form 13 April 1999; accepted 13 April 1999
Abstract To clarify the effects of natural otolith stimulation on muscle sympathetic nerve activity (MSNA) in humans, eight male volunteers were seated in a linear accelerator (sled) during the recording of MSNA from the tibial nerve with microneurography, and also the recording of electrocardiogram, blood pressure measured with a Finapres device and thoracic impedance during movement. Sinusoidal linear acceleration with peak values of ^0.10, 0.15 and 0.20 Gx were applied to the sitting subjects in the anteroposterior direction. Both the total activity and the burst rate of MSNA decreased during the sinusoidal linear acceleration, whereas the average heart rate, thoracic impedance and mean arterial pressure did not change signi®cantly. These results suggest that moderate sinusoidal linear acceleration in the anteroposterior direction may suppress MSNA in humans. q 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Muscle sympathetic nerve activity; Otolith; Microneurography
The sympathetic out¯ow to muscles, which plays an important role in cardiovascular control, is mediated by a number of re¯ex mechanisms. Although some research has focused on the vestibulo-autonomic re¯ex [1,4,8±10,12,14± 18], human studies on the re¯ex controlling the sympathetic out¯ow to muscles have not provided enough data to elucidate the precise mechanism. In our previous studies, we showed that the muscle sympathetic nerve activity (MSNA) from the human tibial nerve is enhanced after caloric vestibular stimulation [2,7], whereas the skin sympathetic nerve activity is suppressed during the nystagmus evoked by the caloric vestibular stimulation [3]. These results suggest that the stimulation of the horizontal semicircular canal has effects on sympathetic out¯ows to muscle and skin in humans. Animal studies showed that the vestibular afferents were involved in blood pressure regulation during postural changes in cats [4]. Yates et al. [15] demonstrated that the neurons in the rostral ventrolateral medulla, which is a major source of excitatory input to sympathetic preganglionic neurons, received vestibular input which appeared to come mainly from otolith receptors in cats. In human studies, MSNA was reported to increase during * Corresponding author. Tel.: 181-52-789-3883; fax: 181-52789-5047. E-mail address: [email protected] (T. Mano)
sustained head-down neck ¯exion, which was considered to be in¯uenced by static input from otolith organs [9,12]. Since an animal study showed that the response patterns of sympathetic nerve activity were related to the direction of the stimulation on the otolith organs [17], we hypothesized that the MSNA response to stimulation of otolith organs in humans in the anteroposterior (naso-occipital or occipitonasal) direction may be different from that in the craniocaudal direction. Furthermore, much less is known about the MSNA response to dynamic acceleratory stimulation of otolith organs in humans. Since otolith organs sense linear acceleration and head orientation with respect to gravity, we used a linear accelerator to stimulate the vestibular organs, especially otolith organs, in sitting subjects in the anteroposterior direction. Following the standard acceleration nomenclature as presented by Glaister [5], the forward acceleration is de®ned as 1Gx, which tends to displace internal tissues such as eyeballs to the occipital direction (`eyeballs in'); while the backward acceleration is de®ned as 2Gx, which tends to displace internal tissues to the nasal direction (`eyeballs out'). We recorded the MSNA from the tibial nerve with microneurography, and observed the hemodynamic responses during movement. Eight healthy male volunteers (mean age ^ SE, 21:8 ^ 0:4 years) participated in the present study. Written informed consent was obtained from each subject. The
0304-3940/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 9 9) 00 36 0- 2
182
J. Cui et al. / Neuroscience Letters 267 (1999) 181±184
Fig. 1. Representative tracings obtained for one subject during baseline, sinusoidal linear acceleration with peak value of ^0.10 Gx and after acceleration. The traces show the acceleration (Gx), instantaneous heart rate (HR), blood pressure (BP), and integrated muscle sympathetic nerve activity (MSNA).
study was approved by the Human Research Committee, Research Institute of Environmental Medicine, Nagoya University. Subjects were seated in a capsule of a linear accelerator (sled), in which a magnetic levitation system is employed at the Research Institute of Environmental Medicine, Nagoya University (Nagoya, Japan). The experimental capsule was sealed against electromagnetic noise and outside light. The subject was strapped into a chair of the capsule, and not only the body but also the head were ®rmly restrained with Velcro tape. The legs were extended at the knee joint in a horizontal position, and the feet were supported at the lower part of the calves with a supporter. Subjects were in a dark environment in the capsule during the experiments. Acceleration in a sinusoidal mode was applied along the anteroposterior (^Gx, naso-occipital and occipito-nasal) directions of subjects with a ®xed moving distance of 14
Table 1 The averages of burst rate and total activity of MSNA, heart rate (HR), thoracic impedance (Impedance), and mean arterial pressure (MAP) before, during and after sinusoidal linear acceleration a Baseline
Acc
MSNA (bursts/min) 23.6 ^ 1.4 13.4 ^ 1.3* MSNA (%) 100 60.1 ^ 5.0* HR (beats/min) 64.6 ^ 1.2 64.3 ^ 1.4 Impedance (V ) 29.1 ^ 0.4 29.2 ^ 0.5 MAP (mmHg) 99.8 ^ 2.2 100.4 ^ 2.3 a
After 1
n
19.0 ^ 1.8 86.4 ^ 9.8 65.3 ^ 1.3 29.1 ^ 0.4 99.5 ^ 2.1
4 4 8 8 8
The results are the averages of the three stimulations, in which the peak acceleration were at ^0.10, ^0.15, ^0.20 Gx. Values are means^SE. Baseline, 1 min before the movement; Acc, the total period of the sinusoidal linear acceleration; after 1, the ®rst minute after the movement stops. n, subject number. *P , 0:05 vs. baseline.
m. In each stimulation, ®ve cyclic movements with the same peak acceleration were repeated continuously. In each subject, three stimulations were applied, with peak values of the sinusoidal acceleration of ^0.10 Gx (0.98 m/s 2), ^0.15 Gx (1.47 m/s 2) and ^0.20 Gx (1.96 m/s 2), respectively. The periods for one cyclic movement with peak accelerations of ^0.10, 0.15 and 0.20 Gx were 16.7, 13.3 and 11.6 s, respectively. The interval between stimulations was 5 min. MSNA was recorded from the right tibial nerve by using microneurography in the same manner as in our previous studies [2,6,7,13]. After the signal was fed into an ampli®er (£50 000) and band-pass ®lters (500,5000 Hz), it was recti®ed and integrated in a resistance-capacitance network with a time constant of 0.1 s. The total activity of MSNA in the present experiments was de®ned as the `burst area' of the integrated neurogram over each second [13]. The ®nal values of total activity of MSNA were expressed in arbitrary units by setting the average value for 1 min before the movement as 100%. MSNA was also expressed as burst rate (burst number per minute). Heart rate was monitored by electrocardiography using a bioelectric ampli®er (AB621G, Nihon Kohden, Tokyo). The blood pressure waveform was recorded with a Finapres 2300 device (Ohmeda, Louisville, CO) on the subject's left or right middle ®nger, which was ®xed with adhesive tape at the level of the right atrium. The mean arterial pressure (MAP) was calculated as the sum of the diastolic blood pressure plus one-third of the pulse pressure in each beat. Subjects were asked to control their respiration rate at 0.25 Hz with a metronome. To estimate changes in intra-thoracic ¯uid volume, thoracic impedance (Zo) was measured with an impedance plethysmograph (AI-601G, Nihon Kohden, Tokyo) with electrodes taped circumferentially around the neck and the chest at the level of the xyphoid process. All signals were stored in a multichannel digital audio tape (DAT) recorder
J. Cui et al. / Neuroscience Letters 267 (1999) 181±184
Fig. 2. Changes in total activity of MSNA during sinusoidal linear acceleration with peak values of ^0.10, ^0.15 and ^0.20 Gx. The total activity of MSNA for the 1 min before the movement was used as the baseline (100%). The MSNA during the sinusoidal linear acceleration with the peak value of ^0.20 Gx was signi®cantly lower than that of ^0.10 Gx acceleration. Base, baseline; 0.10, 0.15, 0.20 Gx, the sinusoidal linear acceleration with peak values at ^0.10, ^0.15, ^0.20 Gx. Subject n 4. *P , 0:01 vs. baseline. #P , 0:005 vs. baseline.
(PC-216A, Sony Precision Technology, Tokyo). The average values of MAP, heart rate and thoracic impedance for 1 min just before the start of the movement served as baseline values. We applied one-way analysis of variance (ANOVA) to assess the changes of the parameters during and after acceleration. The blood pressure, heart rate and thoracic impedance were measured in all subjects. MSNA was recorded successfully in four subjects. Fig. 1 shows the heart rate, blood pressure waveform obtained with the Finapres device and integrated MSNA from the tibial nerve during sinusoidal linear acceleration with peak value of ^0.10 Gx in a representative subject. For the combined data of the three stimulations with the peak accelerations of ^0.10, ^0.15 and ^0.20 Gx, the burst rate and total activity of MSNA decreased signi®cantly compared with the baseline value during sinusoidal linear acceleration (Table 1). For the separate data of the three stimulations, the total activity of MSNA during sinusoidal linear acceleration was also significantly lower than the baseline activity (Fig. 2); while the total activity of MSNA during the sinusoidal linear acceleration with peak value of ^0.20 Gx was signi®cantly lower than that with the peak acceleration ^0.10 Gx (P , 0:05). After acceleration, the MSNA recovered to the baseline level in 1 min. During the sinusoidal linear acceleration, the average MAP, heart rate and thoracic impedance did not change signi®cantly compared to the baseline values for either the separate data or the combined data of the three (^0.10, ^0.15, ^0.20 Gx) stimulations (P . 0:05). There was no complaint of motion sickness symptoms such as nausea, dizziness or cold sweating in any of the subjects. The present data show that sinusoidal linear acceleration in the anteroposterior (naso-occipital and occipito-nasal) directions could suppress sympathetic out¯ow to muscle in sitting humans. This decrease in MSNA can be considered as a combined response to the sinusoidal linear accel-
183
eration, since the results were the average of data obtained when acceleration was in both directions. The decrease in the total activity of MSNA during sinusoidal linear acceleration showed a tendency to depend on the degree of acceleration up to 0.20 Gx. As the average MAP and average thoracic impedance did not change signi®cantly, the decrease in MSNA during sinusoidal linear acceleration could not be considered to be related to the arterial or cardiopulmonary barore¯exes. Since there is considerable evidence that stimulation of the vestibular system has effects on the activities of sympathetic preganglionic neurons in animals and of postganglionic nerves in animals and humans [2±5,7±10,12,14±18], the suppression of the MSNA during ^Gx acceleration in sitting subjects should be considered at least in part as a response evoked by the stimulation of the otolith organs. The decrease in MSNA observed in the present study is different from what was found in our previous studies, in which MSNA was increased during the caloric vestibular stimulation [2,7]. As the caloric vestibular stimulation has an effect on the unilateral semicircular canal and evokes motion sickness symptoms, the MSNA enhancement seen in previous experiments could be considered to be vestibulo-sympathetic responses related to motion sickness, caused partly by an imbalance between the bilateral semicircular canals. The linear acceleration in the present experiments stimulated bilateral otolith organs, and no motion sickness symptoms were observed. The MSNA decrease found in the present study can be considered to be a physiological response in sympathetic out¯ow to muscle during sinusoidal linear acceleration. Our ®nding of a decrease in MSNA in the present study is different from the signi®cant increase in MSNA found by Ray et al. [9] during sustained passive head-down neck ¯exion in the prone position in humans [9,12]. There are several differences in the protocols of the studies by Ray et al. and our study, which may have caused the differences in the results. First, the baseline positions of the subjects were different. The subjects were in a prone position in their studies, but a sitting position in our study. The baseline activity of the otolith organs should be different in these two conditions. Second, the directions of the stimulation were different. In the present experiments, the anteroposterior linear acceleration might mainly alter the utricular afferents [11]; whereas in the neck ¯exion posture, not only utricular afferents but also saccular afferents [11] would have been affected by the changes of the anteroposterior and craniocaudal component of the gravity of the otolith organs. Third, the intensities of the stimulation were different. The maximum change of acceleration in the present study was ^0.20 Gx, whereas the changes in both ^Gx and ^Gz of the otolith organs during the head-down neck ¯exion should have been stronger than those in our study. Fourth, the stimulation in the sinusoidal mode used in the present experiments might cause different responses from sustained stimulation. Therefore, the MSNA response during sinusoidal linear acceleration in the anteroposterior
184
J. Cui et al. / Neuroscience Letters 267 (1999) 181±184
direction might be different from that during head-down neck ¯exion. In conclusion, we observed that the MSNA was suppressed during the moderate sinusoidal linear acceleration in the anteroposterior direction in sitting human subjects. The present data provide useful information on sympathetic out¯ow to muscle in response to natural stimulation of otolith organs in humans. These ®ndings support the concept that otolith organs contribute to cardiovascular regulation in humans. [1] Costa, F., Lavin, P., Robertson, D. and Biaggioni, I., Effect of neurovestibular stimulation on autonomic regulation. Clin. Autonom. Res., 5 (1995) 289±293. [2] Cui, J., Mukai, C., Iwase, S., Sawasaki, N., Kitazawa, H., Mano, T., Sugiyama, Y. and Wada, Y., Response to vestibular stimulation of sympathetic out¯ow to muscle in humans. J. Auton. Nerv. Syst., 66 (1997) 154±162. [3] Cui, J., Iwase, S., Mano, T. and Kitazawa, H., Responses of sympathetic out¯ow to skin during caloric stimulation in humans. Am. J. Physiol., 276 (1999) R738±R744. [4] Doba, N. and Reis, D.J., Role of the cerebellum and vestibular apparatus in regulation of orthostatic re¯exes in the cat. Circ. Res., 34 (1974) 9±18. [5] Glaister, D.H., The effects of long duration acceleration. In J. Ernsting and P. King (Eds.), Aviation Medicine, Butterworths, London, 1988, p. 139. [6] Iwase, S., Mano, T., Watanabe, T., Saito, M. and Kobayashi, F., Age-related changes of sympathetic out¯ow to muscles in humans. J. Gerontol., 46 (1991) M1±M5. [7] Mano, T., Iwase, S., Saito, M., Koga, K., Abe, H., Inamura, K., Matsukawa, Y. and Hashiba, M., Somatosensory-vestibular -sympathetic interactions in man under weightlessness simulated by head-out water immersion. In J.C. Hwang (Ed.), Basic and Applied Aspects of Vestibular Function, Hong Kong University Press, Hong Kong, 1988, p. 193.
[8] Megirian, D. and Manning, J.W., Input-output relations in the vestibular system. Arch. Ital. Biol., 105 (1967) 151±164. [9] Ray, C.A. and Hume, K.M., Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic re¯ex. J. Appl. Physiol., 84 (1998) 450±453. [10] Ray, C.A., Hume, K.M. and Shortt, T.L., Skin sympathetic out¯ow during head-down neck ¯exion in humans. Am. J. Physiol., 273 (1997) R1142±R1146. [11] Schor, R.H. and Tomko, D.L., The vestibular system. In B.J. Yates and A.D. Miller (Eds.), Vestibular Autonomic Regulation, CRC Press, Boca Raton, FL, 1996, p. 7. [12] Shortt, T.L. and Ray, C., Sympathetic and vascular responses to head-down neck ¯exion in humans. Am. J. Physiol., 272 (1997) H1780±H1784. [13] Sugiyama, Y., Matsukawa, T., Suzuki, H., Iwase, S., Shamsuzzaman, A.S. and Mano, T., A new method of quantifying human muscle sympathetic nerve activity for frequency domain analysis. Electroenceph. clin. Neurophysiol., 101 (1996) 121±128. [14] Yates, B.J., Vestibular in¯uences on the sympathetic nervous system. Brain Res. Rev., 17 (1992) 51±59. [15] Yates, B.J., Goto, T. and Bolton, P.S., Responses of neurons in the rostral ventrolateral medulla of the cat to natural vestibular stimulation. Brain Res., 601 (1993) 255±264. [16] Yates, B.J., Grelot, L., Kerman, I.A., Balaban, C.D., Jakus, J. and Miller, A.D., Organization of vestibular inputs to nucleus tractus solitarius and adjacent structures in cat brain stem. Am. J. Physiol., 267 (1994) R974±R983. [17] Yates, B.J. and Millier, A.D., Properties of sympathetic re¯exes elicited by natural vestibular stimulation: implications for cardiovascular control. J. Neurophysiol., 71 (1994) 2087±2092. [18] Yates, B.J., Siniaia, M.S. and Miller, A.D., Descending pathways necessary for vestibular in¯uences on sympathetic and inspiratory out¯ow. Am. J. Physiol., 268 (1995) R1381±R1385.