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Changes in cerebral blood flow estimated after stellate ganglion block by single photon emission computed tomography
Journal of the
ELSEVIER
Journal of the Autonomic Nervous System 50 (1995) 339-346
Autonomic Nervous System
Changes in cerebral blood flow estimated after stellate ganglion block by single photon emission computed tomography Takae Umeyama
a,,, T o y o k i K u g i m i y a a,1 T o k u o O g a w a A k i r a I s h i z u k a c, K a z u o H a n a o k a
b, Y o s h i k a z u d
Kandori
c,
a Department of Anesthesiology, University of Tokyo Branch Hospital, 3-28-6 Mefirodai, Bunkyo-ku, Tokyo 112, Japan, b Department of Physiology, Aichi Medical University, Nagakute, Japan, c Department of Radiology, Aichi Medical University, Nagakute, Japan, d Department of Anesthesiology, University of Tokyo, Tokyo, Japan
Received 4 November 1993; revision received and accepted 10 May 1994
Abstract
The validity of the hypothesis that the cerebral vasculature is under the control of sympathetic innervation was investigated using brain scintigraphy imaging before and after stellate ganglion block (SGB). The experiment with HM-PAO showed a definite increase in the blood flow of the brain on the block side on both by the dynamic images and the SPECT images. The tympanic temperature (Tty) of the block side decreased significantly after SGB, compared to the unblock side in this study, as had been reported before. This change in Try coinsided with the increase in cerebral blood flow as mentioned above. This study demonstrated that the cerebral vasculature is under the control of sympathetic innervation, the pathway of which is relayed and/or passes through the stellate ganglion. We conclude that SGB increases intracerebral blood flow and can also exert secondary effects systemically due to CNS blood flow changes as have been previously reported. Keywords: Stellate ganglion block; Cerebral blood flow; Single photon emission computed tomography; Brain
temperature; Tympanic temperature
I. Introduction
Stellate ganglion block (SGB) causes cutaneous vasodilatation of the head and neck region and the u p p e r limb. This effect has been pre-
* Corresponding author. Tel.: (81-3) 3943-1151. i Present address: Department of Anesthesiology, School of Medicine, Juntendo University, Tokyo, Japan.
sumed to be of major therapeutic importance in the treatment of circulatory and n e u r a l disorders of those regions, where sympathetic control plays a major role. On the other hand, there has been considerable controversy on the physiological significance of sympathetic innervation of the cerebral vasculature. The results of our previous studies [30,31,37,39] have led us to postulate that the cerebral vasculature is under the control of the sympathetic ner-
0165-1838/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved SSDI 0165-1838(94)00105-S
340
T. Umeyama et al. /Journal of the Autonomic NerL,ous System 50 (1995) 339-346
vous system, albeit very subtle, and that this control is largely confined to the ipsilateral hemisphere. In order to further examine sympathetic control of cerebral vasculature, we conducted the present study, where we hypothesized that SGB would induce an increase of blood flow in the ipsilateral hemisphere as estimated by brain scintigraphy.
2. Materials and methods
Subjects were 8 male student volunteers who had given written consent after being informed on the purpose, procedure and risk of the experiment. SGB was performed by injection of 6ml of 1% mepivacaine hydrochloride (Carbocain, Fujisawa) into the vicinity of the base of the right transverse process of the 7th cervical vertebra with the subject lying supine on a scintigraphy table. SGB was judged successful by the appearance of Horner's sign, hemi-facial flushing and a rise in skin temperature of the right arm and hand. Following the SGB, bilateral difference of cerebral blood flow was estimated by single photon emission computed tomography (SPECT) using the radioactive agent [99mTc]hexamethylpropyleneamine oxime (HM-PAO), as tracer [1,22,29,33]. The tracer was used within 5 rain of preparation because of its rapid decomposition in vitro. Dynamic and SPECT images were monitored using gamma-camera equipped with a low-energy collimator (STARCAM 400AC/T, General Electric). The dynamic image was taken over a 10-min interval with the camera set in front of the subject. SPECT was started 30 min after the injection of the nuclide: the camera was moved in a circle around the subject's head, stopping at 64 regular angles where planar images in 64 x 64 matrices were taken for 20 s. The subject was directed to remain relaxed with their eyes closed throughout the maneuver. On the dynamic image, two pairs of symmetric regions of interest (ROIs) were hand-drawn to include the entire right and left brain hemispheres (ROIbrai,-R, -L) and bilateral upper cervical areas (ROIce~-R, -L), to represent areas
Fig. 1. Two pairs of ROIs and a dynamic image of ROlbrain-R, -L and ROIce~-R and -L.
supplied with blood largely from the internal and external carotid arteries, respectively (Fig. 1). Radionuclide counts were averaged every second for 5 rain following HM-PAO injection, and time-activity curves for these ROIs were then processed. Transaxial SPECT slice images, 7.8 mm each in thickness, were taken from the orbito-meatal (O-M) plane to the vertex. Each slice was reconstructed from the information contained in a single row of elements (pixels) in each planar image. Prior to SGB, a bolus dose of 370 MBq of the tracer was injected intravenously, followed by a dynamic study and SPECT. Then SGB was carried out on the right side. After signs that successful SGB had been accomplished, the i.v. bolus of 740 MBq of the radionuclide and scintigraphy was repeated, and a dynamic study and SPECT were repeated. Radioactivity of the preSGB SPECT image was doubled and subtracted from that of the post-SGB image in order to obtain an image that reflected the changes due to SGB. Radionuclide uptake in both the right and the left cerebral hemispheres was measured and projected on transaxial SPECT slices. The bilat-
T. Umeyama et al. / Journal of the Autonomic Nereous System 50 (1995) 339-346
eral difference in radionuclide distribution was then compared between the pre- and post-SGB periods.
34l
The right and the left tympanic temperatures (Tty) were measured simultaneously at 1-min intervals, using temperature probes devised by Ma-
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Fig. 2. Experimental results from one case (R, SGB side; L, non-block side). (A) Time-activity curves of the bilateral ROIbrai n (solid line) and ROleer~ (dotted line) in the dynamic study pre- (thin line) and post-SGB (thick line). (B) Radionuclide count profiles obtained by scanning the SPECT images from the O - M plane to the vertex of the right and left brain hemispheres pre- (thin line) and post-SGB (thick line). (C) Changes in the right and left tympanic temperatures after the SGB (upper line) and the differences between the two temperatures (lower line).
342
72 Umeyama et al. /Journal of the Autonomic Nert:ous System 50 (1995) 339-346
suda and Uchino [23] that have a soft coil spring and a t e m p e r a t u r e monitor with a resolution of 0.01°C ( 1 / 1 0 0 T e m p e r a t u r e Tracer D641, Takara). The placement of the probe on the tympanic m e m b r a n e was judged by the subject's hearing a scratching sound, accompanied by little or no pain. The external auditory meatus was plugged with a piece of absorbent cotton. Because the right and the left Tty are not always equal [32], and because the Tty level varied among the cases and tended to decrease spontaneously as the subject maintained a resting supine posture, the change of Try was expressed as the bilateral difference in the change between Tty on the SGB side and that on the contralatcral side.
3. Results The first two of eight experiments were faulty, due to technical error, i.e., the position of the head was not adequately fixed, and consequently the data were discarded. H e a d positioning was then improved with the aid of laser pointers. The statistical results were obtained from the other six experiments. Fig. 2 shows an example of the time activity curves in 2 pairs of R O I s (ROIbrai n, ROIcerv): (A) S P E C T image of the radionuclide count profiles
% 60- a
--I
504o-
%
30.
2o F o -lO~
*P< 0.05 **P< 0.01 % 20 -k
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0
I L
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Fig. 4. Percent change in total radioactivity in the left and right hemispheres on the SPECT image.
obtained by scanning the right and the left brain hemispheres; (B) the time-course of the right and the left Tty (C, upper) and the time-course of the differences between the right and the left Tty (C, lower). These figures show increased counts of radionuclide in the block side after SGB. While radionuclide count showed a marked increase in the right ROIce ~ after the SGB, radionuclide count in the left ROIc~r~ decreased slightly ( P < 0.05) (Fig. 3a). Radionuclide counts also showed a slightly but significantly greater increase in the right R O I br~in than in the left one where no apparent change was observed ( P < 0.01), suggesting that blood flow increased in the internal carotid artery on the SGB side (Fig. 3b). The S P E C T image showed a considerable increase of blood flow to the brain hemisphere ipsilateral to the SGB side in all 6 cases. The total radionuclide counts increased significantly more on the block side than on the contralateral side ( P < 0.05), where the count failed to show a substantial change (Fig. 4).
2O 10
o L
°C 0
R
Fig. 3. Statistical data from 6 experiments with scintigraphy using [99mTc]HM-PAO.Percent change in average radioactivity from the control value in the ROIs of the right (block side, R) and the left (non-block side, L) upper cervical areas (a) and brain hemispheres (b) on the dynamic image,
•
10
A(Tty-R-Tty-L)
20
30rain
~* p':01O2
Fig. 5. Mean differences of the right and left tympanic temperature after the SGB from 5 cases in which bilateral Tty were measured successfullyfor 30 min.
7". Umeyama et al. /Journal of the Autonomic Nervous System 50 (1995) 339-346
Tty on the ipsilateral side decreased significantly after the block, compared to that on the contralateral side (Fig. 5).
4. Discussion
In the present study we established that SGB caused an increase in blood flow of the internal carotid artery on the side of the block. Prior to this study we performed a preliminary study with a similar protocol using N-isopropyl-p[123I]iodoamphetamine (IMP). While this is an agent which has been widely used for brain imaging because of its high cerebral uptake and its initial distribution being proportional to blood flow [16,20,40], much of IMP which is extracted initially by the lung is moved only gradually to the brain and the liver, the cerebral uptake curve not leveling off until 20 rain after injection [17]. Because we scanned the entire 360 degrees over 30 min, starting from the block side, this would have caused a considerable error in the absolute concentration measurements of the agent due to the time lag. Additionally, because the intracerebral distribution of the agent changes with time, we were unable to obtain the SPECT image prior to SGB as a control. Since cerebral hemispheric asymmetry of blood flow has been seen in resting subjects [5,24,27,34], it could not be concluded that any slight asymmetry observed on SPECT resulted from SGB. A further problem was that unilateral differences in cerebral blood flow might have been too small to detect without control measurements, and this is not feasible with the IMP technique. Because of the drawbacks of the preliminary study, we conducted the present study using HMPAO which has found a rapidly widening usage as an agent for cerebral blood flow scintigraphy because it could be labeled just prior to studies [2,25]. H M - P A O is a lipophilic agent with rapid cerebral uptake at the first circulation after i.v. injection, a distribution in the brain proportional to regional blood flow, and prolonged retention of activity in cerebral structures [2,22,29,33]. The use of this agent avoided the problems of lag to peak concentration and variability of cerebral dis-
343
tributions with time, because it is not incorporated in organs other than the brain. As expected, a significant increase in radionuclide counts on the block side was detected. Anatomically, the stellate ganglion contains the cell bodies of the inferior cervical ganglion, as well as that of the first thoracic sympathetic ganglion. Sympathetic postganglionic fibers which supply the upper arm, neck, face and head originate in the stellate ganglion. The sympathetic preganglionic fibers which make synaptic connection with postganglionic neurons in the upper and middle cervical ganglions pass through the stellate ganglion. The cerebral vasculature is densely supplied with nerve fibers, of which noradrenergic sympathetic ones originating from the superior cervical ganglion have been most extensively studied. They are known to project predominantly to the ipsilateral hemisphere. However, it has been generally considered that the sympathetic innervation of the cerebral vasculature is of minimal importance and its physiological significance has been in controversy [2]. It has been suggested that there is a role for vasomotor nerves in the autoregulation of the cerebral circulation. Some studies report functional variation depending on the brain region and the animal being studied [4,13j4,36]. It has also been proposed that relatively large arterioles, over 50 ~ m in diameter, are under neural control whereas smaller ones are controlled chemically [11], and also that, while extraparenchymal vessels are controlled by sympathetic innervation, intraparenchymal vessels are regulated by local metabolites [12]. Sympathetic innervation of the pial and ocular vasculature has long been recognized [10,21]. The present study evidenced that the cerebral vasculature is under the control of the sympathetic nervous system, the pathway of which is relayed by a n d / o r passes through the stellate ganglion. The brain is metabolically very active and is a heat producing organ similar to the liver where circulating blood functions as a coolant. Consequently, increased blood flow results in a lowering of the brain temperature. One of our most significant observations that led us to conduct the
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T. Umeyama et al. /Journal of the Autonomic Nercous System 50 (1995) 339-346
present study was made by continuous measurement of the bilateral Tty after SGB. These results showed that the Tty on the block side decreased significantly in the range of 0.01 to 0.03°C in 5 rain after the block and that the decrease lasted for 30 min as compared with that on the contralateral side where there was only an expected physiological change. Tty has been used as an indicator of brain temperature [3,6-9,15]. The lower ventral region of the tympanic membrane is supplied with blood from the internal carotid artery. Any decrease in the tympanic temperature may be attributed at least in part to increased internal carotid blood flow. [6]. We also obtained other evidence that SGB causes an increase in internal carotid blood flow: the blood flow of the retino-choroidal arteries, a branch of the internal carotid artery, as measured by oculocerebrovasculometry increased by 20% after SGB [39]. Clinically, SGB has been reported to be beneficial for various ophthalmic disorders, including central epithelial degeneration and leptospirosis of the eyes [26,28,41]. In these disorders, SGB proved to be highly valuable in selection of further treatments, as an outcome predictor, and in prevention of the loss of vision. Evidence has also been presented that changes in blood flow or in the temperature of the perfusing blood due to SGB have effects on hypothalamic function [32,42]. Clinically, SGB has elicited some effects which are difficult to explain on an anatomical basis. From an anatomical standpoint, the effects of SGB should be confined to the upper arm, the head and neck regions. However, SGB which was initially used for disorders in these regions had reportedly resulted in the resumption of menses in patients with hypothalamic amenorrhea [38], in curing insomnia, in improving chilly constitution of the lower extremities and neurogenic pollakiuria [18], in stabilizing the basal body temperature [19], and others. These facts lead us to conclude that SGB increases intracerebral blood flow and can exert beneficial effects systemically secondary to effects on the CNS, especially the hypothalamus. Further studies on the effects of SGB on hypothalamic function should be carried out.
Acknowledgement The authors thank Dr. Douglas Berger and Dr. Akihiro Ogata for helping us to prepare this manuscript.
References [1] Andersen, A.R., 99m-Tc-D,L-hexamethylene-propyleneamine oxime (99mTc-HMPAO): basic kinetic studies of tracer of cerebral blood flow. Cerebrovasc. Brain Metab. Rev., 1 (1989)288-318. [2] Andersen, A.R., Friberg, H., Schmidt, J.F. et al., Quantitative measurements of cerebral blood flow using SPECT and [99rnTc]-D,L-HM-PAO compared to Xenon-133. J. Cereb. Blood Flow Metab. 8 (1988) $69-$81. [3] Benzinger, T.H. and Taylor, G.W., Cranial measurements of internal temperature in man, In: J.D. Hardy (Ed.), Temperature: Its Measurement and Control in Science and Industry, Reinhold, New York, NY, 1972, pp. 111-120. [4] Bevan, J.A., Duckworth, J., Laher, J., Oriowo, M.A., McPherson, G.A. and Bevan, R.D., Sympathetic control of cerebral arteries: specialization in receptor type, reserve, affinity, and distribution, FASEB J., 1 (1987) 193198. [5] Blauenstein, U.W., Halsey, J.H., Wilson, E.M., Wills, E.L. and Risberg, J., 133Xenon inhalation method: Analysis of reproducibility: Some of its physiological implications, Stroke, 8 (1977) 92-102. [6] Brinnel, H. and Cabanac, M., Tympanic temperature is a core temperature in humans, J. Therm. Biol., 14 (1989) 47-53. [7] Cabanac, M. and Caputa, M., Open loop increase in trunk temperature produced by face cooling in working humans, J. Physiol., 289 (1979) 163-174. [8] Cork, R.C., Vaughan, R.W. and Humphrey, L.S., Precision and accuracy of intraoperative temperature monitoring, Anesth. Analg., 62 (1983) 211-214. [9] Dicky, W.T., Ahlgren, E.W. and Stephen, C.R., Body temperature monitoring via the tympanic membrane, Surgery, 67 (1970) 981-984. [10] Ehinger, B., Adrenergic nerve to the eye and to related structures in man and in the cynomologus monkey (Macaca irus), Invest. Opthalmol., 5 (1966) 42-52. [11] Gotoh, F., Fukuuchi, Y., Amano, T., Tanaka, K., Uematsu, D., Suzuki, N., Kobaru, M. and Obara, K., Comparison between pial and intraparenchymal vascular responses to cervical sympathetic stimulation in cats, Part 1. Under normal resting conditions, J. Cereb. Blood Flow Metab. 6 (1986) 342-347. [12] Harper, A.M., Deshmukh, V.D., Rowan, J.O. and Jennett, W.B., The influence of sympathetic nervous activity on cerebral blood flow, Arch. Neurol., 27 (1972) 1-6.
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[13] Heistead, D.D., Marcus, M.L. and Gross, P.M., Effects of sympathetic nerves on cerebral vessels in dog, eat and monkey, Am. J. Physiol., 235 (1978) H544-552. [14] Hernandez-Perez, M.J., Raichle, M.E. and Stone, H.L., The role of the peripheral sympathetic nervous system in cerebral blood flow autoregulation, Stroke, 6 (1975) 284292. [15] Hirata, K., Nagasaka, T., Node, Y. and Nunomura, T., Finger vasodilation correlates better with tympanic than esophageal temperature. Eur. J. Appl. Physiol., 57 (1988) 735-739. [16] Holman, R.H., Hill, T.C., Polak, J.F., Lee, R.G.L., Royal, H.D. and O'Leary, R.H., Cerebral perfusion imaging with iodine-123 labeled amines, Arch. Neurol., 41 (1984) 1060-1066. [17] Holman, B.L., Lee, R.G.L., Hill, T.C., Lovett, R.D. and Lister-James, J., A comparison of two cerebral perfusion tracers, N-isopropyl 1-123 p-iodoamphetamine and 1-123 HIPDM, in the human. J. Nucl. Med., 25 (1984) 25-30. [18] Kageshima, K., Wakasugi, B., Wada, T. and Hajiri, Y., Case report: Stellate ganglion block was effective in 3 patients with neurogenic pollakiuria. Pain Clin., 12 (1982) 781-784 (in Japanese). [19] Kawano, N. and Taneyama, C., A case report of an infertile patient who showed an improvement in basic temperature after stellate ganglion block, 25th General Meeting of Japan Pain Clinic Society, 1991, p. 113 (Abstract in Japanese). [20] Kuhl, D.E., Barrio, J.R., Haung, S.C., Ackermann, R.F., Lear, L.L., Wu, J.L., Lin, T.H. and Phelps, M.E., Quantifying local cerebral blood flow by N-isopropyl-p-[123I iodoamphetamine (IMP) tomography, J. Nucl. Med., 23 (1982) 196-203. [21] Langham, M.E. and Rosenthal, A.R., Role of cervical sympathetic nerve in regulating intraocular pressure and circulation, Am. J. Physiol., 210 (1966) 786-794. [22] Leonard, J.P., Nowotnik, D.P. and Neirinckx, R.D., Technetium-99m-D,L-HM-PAO: A new radiopharmaceutical for imaging regional brain perfusion using SPECT a comparison with iodine-123HIPDM, J. Nucl. Med., 27 (1986) 1819-1823. [23] Masuda, M. and Uchino, K., A device for measuring tympanic membrane temperature in man, Jikeikai Med.J., 25 (1978) 95-99. [24] Matsuda, H., Maeda, T., Yamada, M., Gui, L.X., Tonami, N. and Hisada, K., Age-matched normal values and topographic maps for regional cerebral blood flow measurements by Xe-133 inhalation, Stroke, 15 (1984) 336-341. [25] Matsuda, H., Oba, H., Seki, H., Higashi, S., Sumiya, H., Tsuji, S., Terada, H., Imai, K., Shiba, K., Mori, H. and Hisada, K., Determination of flow and rate constants in a kinetic model of [99mTc]-hexamethyl-propylene amine oxime in the human brain, J. Cereb. Blood Flow Metab., 8 (1988) $61-$68. [26] Matsuura, M., Ando, F. and Matsuura, M., Stellate gan-
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glion block therapy in central serous chorioretinopathy, J. Jpn. Opthalmol. Soc., 85 (1981) 1485-1491 (in Japanese). [27] Mazziotta, J.C., Phelps, M.E., Carson, R.E. and Kuhl, D.E., Tomographic mapping of human cerebral metabolism: Sensory deprivation, Ann. Neurol., 12 (1982) 435444. [28] Nandrup, E., Visudal acuity increased by stellate ganglion block. Case reports, Acta Ophthalmol., 65 (1987) 87-90. [29] Neirinckx, R.D., Canning, L.R., Piper, I.M., Nowotnik, D.P., Pickett, R.D., Holmes, R.A., Voldert, W.A., Foster, A.M., Weisner, P.S., Mariott, J.A. and Chaplin, S.B., Technetium-99m D,L-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion, J. Nucl. Med., 28 (1987) 191-202. [30] Ogawa, T., Sugenoya, J., Ohnishi, N., Natsume K., Imai, K., Kandori, Y., Ishizuka, A. and Osada, A., Effects of body and head positions on bilateral difference in tympanic temperatures, Eur. J. Appl. Physiol., 67 (1993) 354-359. [31] Ogawa, T., Yamashita, Y., Ohnishi, N., Natsume, K., Sugenoya, J. and Imamura, R., Significance of bilateral differences in tympanic temperature, In J.B. Mercer (Ed.), Thermal Physiology 1989, Elsevier, Amsterdam, 1989, pp. 217-222. [32] Ogawa, T., Yamashita, Y., Sugenoya, J., Ohnishi, N., Natume, K., Imai, R., Umeyama, T., Ichiishi, N. and Numata, K., The right and left differences of the tympanic membrane temperature, J. Jpn. Meteorol., 26 (1989) 161-167. [33] Podreka, I., Suess, E., Goldenberg, G., Steiner, M., Brucke, T., Muller, Ch., Lang, W., Neirinckx, R.D. and Deecke, L., Initial experience with Technetium-99m HMPAO brain SPECT, J. Nucl. Med., 28 (1987) 1657-1666. [34] Prohovnik, I., Hakansson, K. and Risberg, J., Observations on the functional significance of regional cerebral blood flow in "resting" normal subjects, Neuropsychologia 18 (1980) 203-217. [35] Rowell, L.B., Human Circulation Regulation During Physical Stress, Oxford University Press, Oxford, 1986. [36] Tuor, U.I., Local distribution of the effects of sympathetic stimulation on cerebral blood flow in the rat, Brain Res., 529 (1990) 224-231. [37] Umeyama, T., Kugimiya, T., Ogawa, T., Ichiishi, N.. Hanaoka, K. and Wakasugi, B., Ipsilateral drop in tympanic temperature following stellate ganglion block. Pain Clin., 13 (1992) 19-21 (in Japanese). [38] Umeyama T., Kugimiya, T., Yoshida, S., Wakasugi, B. and Hanaoka, K., The effect of stellate ganglion block on patients with amenorrhea, J. Jpn. Soc. Clin. Anesth., 14 (1994) 109-114 (in Japanese). [39] Umeyama, T., Ogata, A., Kugimiya, T., Nagahara, M., Nishitateno, K., Hanaoka, K. and Wakasugi, B., The stellate ganglion block and its effects on ophthalmic parameters, Pain Clin., 14 (1993) 221-225 (in Japanese).
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[40] Winchell, H.S., Baldwin, R.M. and Lin, T.H., Development of 1-123-1abeled amines for brain studies: Location of 1-123 iodophenylalkyl amine in rat brain, J. Nucl. Med., 21 (1980) 940-946. [41] Yamashiro, H., Shimada, M., Fukui, S., Fukano, T. and Gotoh, Y., Treatment of chronic retinal artery obstruc-
tion with stellate ganglion block and electric acupuncture, Masui, 39 (1990) 1413-1416 (in Japanese). [42] Yamashita, Y., The relationship between the cooling of the various parts of the head and the tympanic membrane temperature and perspiration reaction, J. Soc. Aichi Med. School, 17 (1989) 6.
ELSEVIER
Journal of the Autonomic Nervous System 50 (1995) 339-346
Autonomic Nervous System
Changes in cerebral blood flow estimated after stellate ganglion block by single photon emission computed tomography Takae Umeyama
a,,, T o y o k i K u g i m i y a a,1 T o k u o O g a w a A k i r a I s h i z u k a c, K a z u o H a n a o k a
b, Y o s h i k a z u d
Kandori
c,
a Department of Anesthesiology, University of Tokyo Branch Hospital, 3-28-6 Mefirodai, Bunkyo-ku, Tokyo 112, Japan, b Department of Physiology, Aichi Medical University, Nagakute, Japan, c Department of Radiology, Aichi Medical University, Nagakute, Japan, d Department of Anesthesiology, University of Tokyo, Tokyo, Japan
Received 4 November 1993; revision received and accepted 10 May 1994
Abstract
The validity of the hypothesis that the cerebral vasculature is under the control of sympathetic innervation was investigated using brain scintigraphy imaging before and after stellate ganglion block (SGB). The experiment with HM-PAO showed a definite increase in the blood flow of the brain on the block side on both by the dynamic images and the SPECT images. The tympanic temperature (Tty) of the block side decreased significantly after SGB, compared to the unblock side in this study, as had been reported before. This change in Try coinsided with the increase in cerebral blood flow as mentioned above. This study demonstrated that the cerebral vasculature is under the control of sympathetic innervation, the pathway of which is relayed and/or passes through the stellate ganglion. We conclude that SGB increases intracerebral blood flow and can also exert secondary effects systemically due to CNS blood flow changes as have been previously reported. Keywords: Stellate ganglion block; Cerebral blood flow; Single photon emission computed tomography; Brain
temperature; Tympanic temperature
I. Introduction
Stellate ganglion block (SGB) causes cutaneous vasodilatation of the head and neck region and the u p p e r limb. This effect has been pre-
* Corresponding author. Tel.: (81-3) 3943-1151. i Present address: Department of Anesthesiology, School of Medicine, Juntendo University, Tokyo, Japan.
sumed to be of major therapeutic importance in the treatment of circulatory and n e u r a l disorders of those regions, where sympathetic control plays a major role. On the other hand, there has been considerable controversy on the physiological significance of sympathetic innervation of the cerebral vasculature. The results of our previous studies [30,31,37,39] have led us to postulate that the cerebral vasculature is under the control of the sympathetic ner-
0165-1838/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved SSDI 0165-1838(94)00105-S
340
T. Umeyama et al. /Journal of the Autonomic NerL,ous System 50 (1995) 339-346
vous system, albeit very subtle, and that this control is largely confined to the ipsilateral hemisphere. In order to further examine sympathetic control of cerebral vasculature, we conducted the present study, where we hypothesized that SGB would induce an increase of blood flow in the ipsilateral hemisphere as estimated by brain scintigraphy.
2. Materials and methods
Subjects were 8 male student volunteers who had given written consent after being informed on the purpose, procedure and risk of the experiment. SGB was performed by injection of 6ml of 1% mepivacaine hydrochloride (Carbocain, Fujisawa) into the vicinity of the base of the right transverse process of the 7th cervical vertebra with the subject lying supine on a scintigraphy table. SGB was judged successful by the appearance of Horner's sign, hemi-facial flushing and a rise in skin temperature of the right arm and hand. Following the SGB, bilateral difference of cerebral blood flow was estimated by single photon emission computed tomography (SPECT) using the radioactive agent [99mTc]hexamethylpropyleneamine oxime (HM-PAO), as tracer [1,22,29,33]. The tracer was used within 5 rain of preparation because of its rapid decomposition in vitro. Dynamic and SPECT images were monitored using gamma-camera equipped with a low-energy collimator (STARCAM 400AC/T, General Electric). The dynamic image was taken over a 10-min interval with the camera set in front of the subject. SPECT was started 30 min after the injection of the nuclide: the camera was moved in a circle around the subject's head, stopping at 64 regular angles where planar images in 64 x 64 matrices were taken for 20 s. The subject was directed to remain relaxed with their eyes closed throughout the maneuver. On the dynamic image, two pairs of symmetric regions of interest (ROIs) were hand-drawn to include the entire right and left brain hemispheres (ROIbrai,-R, -L) and bilateral upper cervical areas (ROIce~-R, -L), to represent areas
Fig. 1. Two pairs of ROIs and a dynamic image of ROlbrain-R, -L and ROIce~-R and -L.
supplied with blood largely from the internal and external carotid arteries, respectively (Fig. 1). Radionuclide counts were averaged every second for 5 rain following HM-PAO injection, and time-activity curves for these ROIs were then processed. Transaxial SPECT slice images, 7.8 mm each in thickness, were taken from the orbito-meatal (O-M) plane to the vertex. Each slice was reconstructed from the information contained in a single row of elements (pixels) in each planar image. Prior to SGB, a bolus dose of 370 MBq of the tracer was injected intravenously, followed by a dynamic study and SPECT. Then SGB was carried out on the right side. After signs that successful SGB had been accomplished, the i.v. bolus of 740 MBq of the radionuclide and scintigraphy was repeated, and a dynamic study and SPECT were repeated. Radioactivity of the preSGB SPECT image was doubled and subtracted from that of the post-SGB image in order to obtain an image that reflected the changes due to SGB. Radionuclide uptake in both the right and the left cerebral hemispheres was measured and projected on transaxial SPECT slices. The bilat-
T. Umeyama et al. / Journal of the Autonomic Nereous System 50 (1995) 339-346
eral difference in radionuclide distribution was then compared between the pre- and post-SGB periods.
34l
The right and the left tympanic temperatures (Tty) were measured simultaneously at 1-min intervals, using temperature probes devised by Ma-
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Fig. 2. Experimental results from one case (R, SGB side; L, non-block side). (A) Time-activity curves of the bilateral ROIbrai n (solid line) and ROleer~ (dotted line) in the dynamic study pre- (thin line) and post-SGB (thick line). (B) Radionuclide count profiles obtained by scanning the SPECT images from the O - M plane to the vertex of the right and left brain hemispheres pre- (thin line) and post-SGB (thick line). (C) Changes in the right and left tympanic temperatures after the SGB (upper line) and the differences between the two temperatures (lower line).
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72 Umeyama et al. /Journal of the Autonomic Nert:ous System 50 (1995) 339-346
suda and Uchino [23] that have a soft coil spring and a t e m p e r a t u r e monitor with a resolution of 0.01°C ( 1 / 1 0 0 T e m p e r a t u r e Tracer D641, Takara). The placement of the probe on the tympanic m e m b r a n e was judged by the subject's hearing a scratching sound, accompanied by little or no pain. The external auditory meatus was plugged with a piece of absorbent cotton. Because the right and the left Tty are not always equal [32], and because the Tty level varied among the cases and tended to decrease spontaneously as the subject maintained a resting supine posture, the change of Try was expressed as the bilateral difference in the change between Tty on the SGB side and that on the contralatcral side.
3. Results The first two of eight experiments were faulty, due to technical error, i.e., the position of the head was not adequately fixed, and consequently the data were discarded. H e a d positioning was then improved with the aid of laser pointers. The statistical results were obtained from the other six experiments. Fig. 2 shows an example of the time activity curves in 2 pairs of R O I s (ROIbrai n, ROIcerv): (A) S P E C T image of the radionuclide count profiles
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obtained by scanning the right and the left brain hemispheres; (B) the time-course of the right and the left Tty (C, upper) and the time-course of the differences between the right and the left Tty (C, lower). These figures show increased counts of radionuclide in the block side after SGB. While radionuclide count showed a marked increase in the right ROIce ~ after the SGB, radionuclide count in the left ROIc~r~ decreased slightly ( P < 0.05) (Fig. 3a). Radionuclide counts also showed a slightly but significantly greater increase in the right R O I br~in than in the left one where no apparent change was observed ( P < 0.01), suggesting that blood flow increased in the internal carotid artery on the SGB side (Fig. 3b). The S P E C T image showed a considerable increase of blood flow to the brain hemisphere ipsilateral to the SGB side in all 6 cases. The total radionuclide counts increased significantly more on the block side than on the contralateral side ( P < 0.05), where the count failed to show a substantial change (Fig. 4).
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Fig. 3. Statistical data from 6 experiments with scintigraphy using [99mTc]HM-PAO.Percent change in average radioactivity from the control value in the ROIs of the right (block side, R) and the left (non-block side, L) upper cervical areas (a) and brain hemispheres (b) on the dynamic image,
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Fig. 5. Mean differences of the right and left tympanic temperature after the SGB from 5 cases in which bilateral Tty were measured successfullyfor 30 min.
7". Umeyama et al. /Journal of the Autonomic Nervous System 50 (1995) 339-346
Tty on the ipsilateral side decreased significantly after the block, compared to that on the contralateral side (Fig. 5).
4. Discussion
In the present study we established that SGB caused an increase in blood flow of the internal carotid artery on the side of the block. Prior to this study we performed a preliminary study with a similar protocol using N-isopropyl-p[123I]iodoamphetamine (IMP). While this is an agent which has been widely used for brain imaging because of its high cerebral uptake and its initial distribution being proportional to blood flow [16,20,40], much of IMP which is extracted initially by the lung is moved only gradually to the brain and the liver, the cerebral uptake curve not leveling off until 20 rain after injection [17]. Because we scanned the entire 360 degrees over 30 min, starting from the block side, this would have caused a considerable error in the absolute concentration measurements of the agent due to the time lag. Additionally, because the intracerebral distribution of the agent changes with time, we were unable to obtain the SPECT image prior to SGB as a control. Since cerebral hemispheric asymmetry of blood flow has been seen in resting subjects [5,24,27,34], it could not be concluded that any slight asymmetry observed on SPECT resulted from SGB. A further problem was that unilateral differences in cerebral blood flow might have been too small to detect without control measurements, and this is not feasible with the IMP technique. Because of the drawbacks of the preliminary study, we conducted the present study using HMPAO which has found a rapidly widening usage as an agent for cerebral blood flow scintigraphy because it could be labeled just prior to studies [2,25]. H M - P A O is a lipophilic agent with rapid cerebral uptake at the first circulation after i.v. injection, a distribution in the brain proportional to regional blood flow, and prolonged retention of activity in cerebral structures [2,22,29,33]. The use of this agent avoided the problems of lag to peak concentration and variability of cerebral dis-
343
tributions with time, because it is not incorporated in organs other than the brain. As expected, a significant increase in radionuclide counts on the block side was detected. Anatomically, the stellate ganglion contains the cell bodies of the inferior cervical ganglion, as well as that of the first thoracic sympathetic ganglion. Sympathetic postganglionic fibers which supply the upper arm, neck, face and head originate in the stellate ganglion. The sympathetic preganglionic fibers which make synaptic connection with postganglionic neurons in the upper and middle cervical ganglions pass through the stellate ganglion. The cerebral vasculature is densely supplied with nerve fibers, of which noradrenergic sympathetic ones originating from the superior cervical ganglion have been most extensively studied. They are known to project predominantly to the ipsilateral hemisphere. However, it has been generally considered that the sympathetic innervation of the cerebral vasculature is of minimal importance and its physiological significance has been in controversy [2]. It has been suggested that there is a role for vasomotor nerves in the autoregulation of the cerebral circulation. Some studies report functional variation depending on the brain region and the animal being studied [4,13j4,36]. It has also been proposed that relatively large arterioles, over 50 ~ m in diameter, are under neural control whereas smaller ones are controlled chemically [11], and also that, while extraparenchymal vessels are controlled by sympathetic innervation, intraparenchymal vessels are regulated by local metabolites [12]. Sympathetic innervation of the pial and ocular vasculature has long been recognized [10,21]. The present study evidenced that the cerebral vasculature is under the control of the sympathetic nervous system, the pathway of which is relayed by a n d / o r passes through the stellate ganglion. The brain is metabolically very active and is a heat producing organ similar to the liver where circulating blood functions as a coolant. Consequently, increased blood flow results in a lowering of the brain temperature. One of our most significant observations that led us to conduct the
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T. Umeyama et al. /Journal of the Autonomic Nercous System 50 (1995) 339-346
present study was made by continuous measurement of the bilateral Tty after SGB. These results showed that the Tty on the block side decreased significantly in the range of 0.01 to 0.03°C in 5 rain after the block and that the decrease lasted for 30 min as compared with that on the contralateral side where there was only an expected physiological change. Tty has been used as an indicator of brain temperature [3,6-9,15]. The lower ventral region of the tympanic membrane is supplied with blood from the internal carotid artery. Any decrease in the tympanic temperature may be attributed at least in part to increased internal carotid blood flow. [6]. We also obtained other evidence that SGB causes an increase in internal carotid blood flow: the blood flow of the retino-choroidal arteries, a branch of the internal carotid artery, as measured by oculocerebrovasculometry increased by 20% after SGB [39]. Clinically, SGB has been reported to be beneficial for various ophthalmic disorders, including central epithelial degeneration and leptospirosis of the eyes [26,28,41]. In these disorders, SGB proved to be highly valuable in selection of further treatments, as an outcome predictor, and in prevention of the loss of vision. Evidence has also been presented that changes in blood flow or in the temperature of the perfusing blood due to SGB have effects on hypothalamic function [32,42]. Clinically, SGB has elicited some effects which are difficult to explain on an anatomical basis. From an anatomical standpoint, the effects of SGB should be confined to the upper arm, the head and neck regions. However, SGB which was initially used for disorders in these regions had reportedly resulted in the resumption of menses in patients with hypothalamic amenorrhea [38], in curing insomnia, in improving chilly constitution of the lower extremities and neurogenic pollakiuria [18], in stabilizing the basal body temperature [19], and others. These facts lead us to conclude that SGB increases intracerebral blood flow and can exert beneficial effects systemically secondary to effects on the CNS, especially the hypothalamus. Further studies on the effects of SGB on hypothalamic function should be carried out.
Acknowledgement The authors thank Dr. Douglas Berger and Dr. Akihiro Ogata for helping us to prepare this manuscript.
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