AMERICAN JOUENAL Vol. 231, No. 1, July
OF
hYt3IOLAXY
1976.
Printed
in U.SA.
Hypothalamic and thalamic blood flow during afferent stimulation in dogs PETER
SANDOR, IVAN T. DEMCHENKO, ARISZTID MOSKALENKO Experimental Research Department, Semmelweis Medical
SANDOR, PETER, IVAN T. DEMCHENKO, ARISZTID G. B. KOVACH, AND YURIJ E. MOSKALENKO. Hypothalamic and thalamic blood flow during somatic afferent stimulation in dogs. Am. J. Physiol. 231(l): 270-274. 1976. -The effect of somatic afferent C fiber stimulation on regional cerebral blood flow (rCBF) and cerebral tissue available oxygen (a@) was studied in 20 dogs under chloralose anesthesia. Mean arterial blood before and pressure, arterial Pco2, and pH were stabilized during the 3-min stimulation of the sciatic nerves (20 V, 300 ms, 15 Hz). Combined gold +platinum electrodes were chronically implanted into the ventral posterolateral nucleus of the thalamus, ventromedial nucleus of the hypothalamus, and into the white matter. Tissue aOz and rCBF of these regions were measured polarographically, the latter by the Hz-gas clearance technique. Blood flow changed from 42 5 2.1 to 28 t 1.7 ml/100 g per min (cerebrovascular resistance (CVR), from 2.9! t 0.29 to 4.31 -e 0.52 resistance units (RU) in the thalamus, corn 59 t, 5.0 to 47 2 5.0 ml1100 g per min (CVR: from 2.46 t 0.28 to 2.92 +: 0.35 RU) in the hypothalamus, and from 21 t 1.0 to 17 t, 0.8 ml/l00 g per min (CVR: from 6.367 t 0.35 to 7.672 t 0.40 RU) in the awhite matter during ipsilateral stimulation. Contralateral stimulation of the sciatic nerves caused a more moderate but likewise significant drop in rCBF and an increase in CVR except in the white matter. Parallel to these changes, tissue a0, decreased by 25 t, 2% in the thalamic and by 19 2 2% in the hypothalamic area, relative to the prestimulation level. rCBF; neural
control;
G. B. KOVACH, University,
AND
somatic
YURIJ
1082, Budapest,
E.
Hungary
nerve stimulation results in functional changes, as well, i.e., a specific type of evoked potentials can be recorded in the hypothalamus as shown by Dora et al. (8). In spite of these data, one of the most important questions is still open: does the anatomically abundant innervation of the dural and pial vessels and of the intracerebral arterioles have any functional role in the resting tone of the cerebrovascular smooth muscle and in autoregulation of the CBF? In addition to the inherent theoretical difficulties of this question, several methodological considerations present a problem. Thus, there are a great number of contradictory data concerning the effect of nerve stimulation on CBF. The current controversy over sympathetic cerebral vasoconstriction, for instance, is well characterised by the papers of D’Alecy and Feigl(6) and Traystman and Rapela (34). The disagreement may be due in part to the fact that a considerable number of the studies were performed under conditions in which either cerebral perfusion pressure (i.e., MABP) or arterial Pco2 was not controlled. Changes in these parameters occurred during stimulation, and the results are therefore misleading. Any increase in arterial pressure or in arterial Pcoll value can decrease or even totally obscure any vasoconstrictor effect of the stimulation. The aim of our present work was to study the effect of nociceptive somatic afferent stimulation on the local thalamic and hypothalamic blood flow and tissue available oxygen (aO,> in dogs at constant arterial blood pressure, Pco~, and pH.
tissue a0,; Hz-gas clearance
SINCE THE CLASSIC STUDIES of Nothnagel
and Hurtle (13, 27) in the last century and Chorobski and Penfield (4) in the early 1930’s, an increasing number of studies have demonstrated both sympathetic (1, 5, 9, 14, 20, 24, 26, 29-31, 33) and parasympathetic (12, 17, 18, 23, 25, 28) mechanisms involved in cerebrovascular control. Kovach et al. (16) in 1954 showed that in cross-circulation experiments, in which the brain of the recipient dog was hemodynamically isolated from the trunk and perfused by a donor dog, epinephrine or norepinephrine injection to the recipient’s trunk caused a significant increase in its total cerebral blood flow. The effect of somatic afferent impulses in the regulation of CBF has been much less studied than the role of the vegetative nerves. According to some recent data (Salford (32), Matrosov (22)), somatic tierent stimulation causes significant changes in the distribution of the lactate and catecholamine content of the brain. In addition to the changes in the chemical composition, sciatic
METHODS
The experiments were performed on 20 dogs of both sexes weighing 8-13 kg, anesthetized with 100 mg/kg iv of chloralosel; 4-6 days before the experiments combined platinum + gold electrodes were implanted according to Lim, Liu, and Moffit’s stereotaxic atlas (19) into the ventral posterolateral nucleus of the thalamus (R:18, L:8, V:16 mm) and into the ventromedial nucleus of the hypothalamus (R:19, L:2, V:6 mm) in order to determine regional blood flow and tissue a0, in these areas. The diameter of the double electrode was 200 Frn, and it was insulated with Araldite* or Teflon? The length of the 1 cr-o/+/-gluco-chloralose, E. Merck AG, Darmstadt, West Germany. * Araldite, CIBA (A. R. L.) Ltd. Duxford, Cambridge, England. 3 Medwire Corp., Mt. Vernon, N.Y. 97n
Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (149.171.067.148) on January 1, 2019.
EFFECT
OF
SOMATIC
AFFERENT
STIMULATION
ON
RCBF
AND
TISSUE
271
A@
active surface of the electrode tip was 1.5 mm. Both min. Since arterial blood pressure was kept constant tissue a0, and regional cerebral blood flow measure- and showed practically no change, reduced blood flow ments were performed polarographically, the latter in- must be a consequence of the marked 48% increase in termittently, by using Aukland’s (2) hydrogen-gas peripheral vascular resistance in this area. clearance technique and recorded on Kipp BD-5 microContralateral stimulation gave rise to a similar but graphs (Kipp and Zonen, DelR, Holland). Tissue a0, somewhat more moderate effect. The 27% decrease in changes were measured continuously and were ex- thalamic blood flow was associated with a 40% increase pressed in percentage changes relative to the prestimuin cerebrovascular resistance. The changes in CVR and lation level (100%). A zero a0, value was obtained after regional CBF were significant, whereas MABP, arterial stopping the heart with KC1 and switching the respiraPcop, and pH showed no significant alterations. tor off at the end of the experiments. Cerebral blood flow Hypothalamic blood flow changes. Cerebrovascular values were calculated by the 2-min initial slope tech- resistance in the ventromedial hypothalamic area rose nique and were expressed in milliliters per 100 g per by 22% under the effect of ipsilateral and by 23% under minute. Cerebrovascular resistance (CVR) was ex- that of contralateral somatic afferent stimulation (Tapressed in resistance units (RU) and calculated as fol- ble 2). Hypothalamic blood flow decreased by 18% in both cases (control values: 59 t 5.0, respectively, 80 t lows: CVRF=MABP mmHg/flow ml per 100 g per min. The mean arterial blood pressure (MABP) value used in 7.0 ml/100 g per min). These changes are statistically this calculation was determined in the middle of the 2.0- significant. At the same time the controlled parameters min initial slope, period. (MABP, arterial Pcoz, and pH) remained unaltered. Sciatic nerves were prepared on both sides in order to stimulate somatic afferent C fibers. The nerve was TABLE 1. Effect of ipsi- and contralateral sciatic slightly elevated by the stimulating electrode and was nerve stimulation on thalamic blood flow and vascular resistance in MABP, arterial electrically isolated from its surrounding with a paraffin oil pool. The parameters of stimulation were 20 V, Pco~, and arterial pH-stabilized dogs 300 ms, 15 Hz for 3 min (S 44 stimulator, Grass InstruNo. Side of ment Co., Quincy, Mass.). Arterial blood pressure was Parameter Before Stim. j During Stim. IYtFz of P Stimulation 3tim stabilized with an Engelking and Willig’s (10) modified buffer reservoir system and was monitored on a polyIpsiMABP, mmHg 1222 13 I 11329 I -7 7 BO.4 lateral Flow, ml/100 g 4222.1 28tl.7 -33 7 co.001 graph (Visiograph, Alvar Electronics, Paris). Heparin4 per min was given intravenously in a dose of 500 IU/kg. In order CVR, RU 2.91kO.29 4.31k0.52 +48 co.001 to stabilize arterial blood Pco? and pH levels, the dogs Arterial Pco2, 3721.1 36k1.3 -2 >0.3 were immobilized with Flaxedy15 (2 mg/kg iv), and the mmHg I I rate and volume of artificial respiration (Harvard dual Arterial pH 7.27kO.03 7.26kO.03 0 >0.2 phase control pump, Harvard Apparatus Co., Millis, MABP, mmHg 12627 12326 -2 >0.3 Mass. > were adjusted according to changes of the Pco2 Contralateral Flow, ml/100 g 48k6.1 3422.8 -27 co.01 level in the expired air, measured conti nuously by per min means of an infrared gas analyzer (Godart-Statham CVR, RU 2.859kO.36 3.81320.39 +40 0.9 co.001
7.67220.40 35kl.l
+24 -3
26 18
co.01 BO.4
24
>0.5
+2 +5
13 13
BO.1 >0.9
) -8 -5
13 18
>0.7 >0.3
9
>0.7
7.3hO.02 12427 i3k2.3 5.246k0.58 3521.7 7.32kO.01
0
0
tissue 120
DEMCHENKO,
KOVACH,
AND
MOSKALENKO
a02 %
1 cqntfalateral
III
time in see
1111
0 6 12
30
11 45
60
11
I
I1
L A TI 0 N
FIG. 1. Effect of ipsilateral and contralateral lation on thalamic tissue a0, (12 ipsilateral stimulation in 7 dogs). a02
I
90 105 120 135 150 165 180 195 205
75
W’t’MLJ
tissue no
1
-
sciatic nerve stimuand 10 contralateral
Z
1T
110
90
80
time in stc
lrrI1111 0 6 12
30
45
60
75
SO
I1 105
111111
120 135 150 165 180 1%
205
STIMULATION FIG. 2. Effect of ipsilateral lation on hypothalamic tissue stimulation in 5 dogs).
and contralateral a0, (12 ipsilateral
sciatic nerve stimuand 10 contralateral
DISCUSSION
Regional cerebral blood flow changes were studied in the VPL nucleus thalami and in the ventromedial nucleus of the hypothalamus. Changes in these regions were compared to those in the white matter. These regions were chosen for study because they play an important role either as relay stations for afferent neural impulses or as centers controlling specific cardiovascular functions. The parameters of prolonged sciatic nerve stimulation were the same as those used by Evans (11): According to his data, one can stimulate in this way, with careful preparation, the somatic afferent C fibers carrying nociceptive impulses to the CNS. One can presume that if C fiber stimulation causes changes in the regional distribution of cerebral blood flow, this can also happen in pathologic conditions under which somatic afferentation is increased in painful injuries. According to the above results, local peripheral resistance increased and local bloodsflow\ decreased in each
Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (149.171.067.148) on January 1, 2019.
EFFECT
OF
SOMATIC
AFFERENT
STIMULATION
ON
RCBF
area studied under the influence of prolonged ipsilateral sciatic nerve stimulation. Blood flow decreased more in the thalamic than in the hypothalamic area, and the smallest changes were observed in the white matter. It should be emphasized that the results presented here were obtained in dogs whose blood pressure, arterial Pcop, and pH were controlled. In some experiments the continuous control of these parameters temporarily failed. In these cases a marked increase in rCBF and tissue a0, was noted simultaneously with a significant elevation of mean arterial pressure during stimulation in each region studied. This observation supports our opinion and that of others (James, Millar, and Purves (15)) that it is of great importance to have a steady state with respect ‘to blood gas tensions and mean arterial pressure in studies of neurogenic control. Since neither local arterial nor local venous pressure was recorded in the experiments, it was not possible to calculate the absolute perfusion pressure values. Nevertheless, one can get a reasonable estimate of the relative changes in regional cerebrovascular resistance by calculating the MABP/rCBF r:ltio. The control flow values obtained in our experiments are in good accordance with the average “resting” flow values of the grey and white matter in anesthetized dogs, reported by Lubbers (21). However, there was a considerable difference between the control hypothalamic flow values measured in the ipsilaterally and contralaterally stimulated groups (Table 2). Mean arterial blood pressure was about the same in both experimental groups (138 and 131 mmHg), but in the contralaterally stimulated group we measured high hypotha-
AND
TISSUE
273
Ao2
lamic control blood flow values in 3 out of 10 cases (84, 87, and 77 ml/l00 g per min, in 2 animals). This may be the reason for the relatively high resting flow value of this group. In four experiments, 5 mg/kg of phenoxyben.zamine6 were administered intravenously to the dogs in the second phase of the study, and sciatic nerve stimulation was repeated after 30 min. MABP decreased to about 70-80 mmHg, rCBF and blood gas values were unchanged after administration of phenoxybenzamine, and sciatic nerve stimulation caused no rCBF changes in any of the cerebral regions studied (7). Tissue a0, decreased both in the thalamic and in the hypothalamic region during somatic afferent stimulation. As in the case of local blood flow changes, ipsilatera1 stimulation was more effective than contralateral. According to our data, the amplitude of a0, oscillations in brain tissue decreases significantly during somatic afferent stimulation, whereas frequency remains unchanged. These changes are presented and discussed in detail in another paper (7). Our results corroborate the view of Burgess (3) that oxygen cycles are not random and independent but that they are coupled from some central source. This work was supported in part by National Institute of Neurological Diseases and Stroke Grant NS 10939-01. Current address of I. T. Demchenko and Y. E. Moskalenko: Cerebrovascular Research Laboratory, Sechenov Institute of Evolutionary Physiology and Biochemistry, Union of Soviet Socialist Republics Academy of Sciences, Leningrad, U.S.S.R. Received
for publication
28 July
1975.
REFERENCES 1. ANGELAKOS, E. T., M. P. KING, J. T. PONESSA, AND J. D. IRVIN. Adrenergic innervation of brain vessels in certain regions of the central nervous system. Stroke 4: 369, 1973. 2. AUKLAND, K., B. F. BOWER, AND R. W. BERLINER. Measurement of local blood flow with hydrogen gas. CircuZation Res. 14:164187, 1964. 3. BURGESS, D. W. Correlation between oxygen cycles in contralatera1 regions of the brain. Stroke 4: 374, 1973. 4. CHOROBSKI, J., AND W. PENFIELD. Cerebral vasodilator nerves and their pathway from the medulla oblongata. Arch. NeuroZ. Psychiat. 28: 1257-1289, 1932. 5. DAHL, E., AND E. NELSON. Electron microscopic observations on human intracranial arteries. II. Innervation. Arch. Neural. 10: 158-164, 1964. 6. D’ALECY, L. G., AND E. 0. FEIGL. Sympathetic control of cerebral blood flow in dogs. CircuZation Res. 31: 267-283, 1972. 7. DEMCHENKO, I. T., P. SANDOR, Y. E. MOSKALENKO, AND A. G. B. KOVACH. Cerebral blood flow and cerebral tissue PO, changes during somatic afferent stimulation. Sechenov Physiol. J. USSR 8: 1153-1159, 1975. 8. DORA, E., A. G. B. KOVACH, AND I. NYP~RY. Hypothalamic and cortical evoked potentials in haemorrhagic shock. In: Neurohumoral and MetaboZic Aspects of Injury, edited by A. G. B. Kov&h, H. G. Stoner, and J. J. Spitzer. New York: Plenum, 1973, p. 481-488. 9. EKSTR~M-JODAL, B., C. VON ESSEN, E. H~~GGENDAL, AND B. E. Roes. Effects of noradrenaline, 5-hydroxytryptamine and dopamine on the cerebral blood flow in the dog. Stroke 4: 367-368, 1973. lo. ENGELKING, R., AND F. WILIJG. Uber eine Methode zur Konstanthaltung des Blutdruckes im Tierexperiment. Pfluegers Arch. 267: 306-312, 1958. 11. EVANS, M. H. The spinal pathways of the myelinated and the
12.
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16.
17. 18. 19. 20.
21.
22.
non-myelinated afferent nerve fibres that mediate reflex dilatation of the pupils. J. Physiol., London 158: 560-572, 1961. HARPER, A. M., V.-D. DESMUKH, J. 0. ROWAN, AND W. B. JENNETT. Studies on possible neurogenic influences on the cerebral circulation. In: Brain and BZood Flow, edited by R. W. Ross Russell. London: Pitman, 1971, p. 182-186. HURTLE, K. Beitrage zur Hamodynamik. 3. Abhandlung: Untersuchung uber die Innervation der Hirngefasse. Pfluegers Arch. 44: 561-618, 1889. IWAYAMA, T., J. B. FURNESS, AND G. BURNSTOCK. Dual adrenergic and cholinergic innervation of the cerebral arteries of the rat. CircuZation Res. 26: 635-646, 1970. JAMES, I. M., R. A. MILLAR, AND M. J. PURVES. Observations on the extrinsic neural control of cerebral blood flow in the baboon. CircuZation Res. 25: 77-93, 1969. KOY~CH, A. G. B., P. R~HEIM, AND M. IRP~NYI. Uber vasomotorische Reflexe, die vom Kopf- oder Korperkreislauf auslosbar sind. Acta PhysioZ. Acad. Sci. Hung. 6, Suppl. 27-28, 1954. KUSCHINSKY, W., AND M. WAHL. Cholinergic receptors at pial arteries. A microapplication study. Stroke 4: 371, 1973. LICATA, R. H., D. OLSON, AND E. MACK. Cholinergic and adrenergic innervation of cerebral vessels. Stroke 4: 370-371, 1973. LIM, R. K. S., C. N. LIU, AND R. L. MOFFITT. A Stereotaxic AtZas of the Dog’s Brain. Springfield: Thomas, 1960, p. 93. LLUCH, S., B. GOMEZ, E. ALBORCH, M. MANRIQUE, AND P. URQUILLA. Sympathetic control of the cerebral blood flow in the &anesthetized goat. Stroke 4: 367, 1973. LOBBERS, D. W. Physiologie der Gehirndurchblutung. In: Der Hirnkreislauf’, edited by H. Ganshirt. Stuttgart: Georg Thieme, 1972, p. 214-260. MATROSOV, V. D. The effect of sustained nociceptive stimulation 6 Dibenzyline,
Smith
Kline
8~ French,
Philadelphia,
Pa.
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SANDOR, on the adrenalin and noradrenalin ,contents in different brain areas and in arena1 glands of rats prior to and after removal of the upper cervical sympathetic ganglia. Sechenov Physiol. J.
USSR’ 3: 385-390, 23. MCHEDLISHVILI,
1975.
G. I., and L. S. NIKOLAISHVILI. Evidence of a cholinergic ‘nervous mechanism mediating the autoregulatory dilation of the cerebral blood vessels. Pfluegers Arch. 315: 27-37,
1970. 24. MCNAUGHTON,
F. L. The innervation of the intracranial blood vessels and dural sinuses. Res. Publ. Ass. Res. Nerv. Ment. Dis.
18: 178-189, 1937. 25. NIELSEN, K., C., L. EDVINSSON,
AND C. H. OWMAN. Cholinergic innvervation of the pial arterial system. Stroke 4: 371, 1973. 26. NIELSEN, K. C., AND C. OWMAN. Adrenergic innervation of pial arteries related to the circle of Willis in the cat. Brain Res. 6:
773-776, 1967. 27. NOTHNAGEL,
H. Die vasomotorischen Nerven der Gehirnfasse. (Beitrag zur Lehre von der Epilepsie.) Virchows Arch. Puthol. Anat. 1: -203-213, 1867. 28. PLETCHKOVA, E. K., G. I. MCHEDLISHVILI, N. B. LAVRENTIEVA, AND L. S. NIKOLAISHVILI. Evidence for a cholinergic mechanism responsible for the functional hyperemia in the cerebral cortex.
DEMCHENKO,
KOVACH,
AND MOSKALENKO
In: Correlation of Blood Supply with Metabolism and Function, edited by G. I. Mchedlishvili. Tbilisi: Georgian Acad. Press Metsniereba, 1969, p. 172-184. 29. PONE~WA, J.T.,P. SANDOR, A; G.B. KOVLCH, AND E.T. ANGELAKOS. The effect of cervical sympathectomy on regional brain blood flow during haemorrhagic shock. Physiologist 17: 309, 1974. 30. PONE~~A, J. T., El T. ANGELAKOS.
P. SANDOR, A. G. B. KOVACH, M. P. KING, AND Effect of sympathetic stimulation on regional brain blood flow. Physiologist 15: 239, 1972. 31. ROSEND~RFF, C., G. MITCHELL, AND D. R. L. SCRIVEN. Evidence for the adrenergic control of the cerebrovascular tone. Stroke 4: 368, 1973. 32. SALFORD,
L. G., T. E. DUFFY, AND F. PLUM. Altered cerebral metabolism and blood flow in response to physiological stimulation. Stroke 4: 361-362, 1973. 33. S~~HR, P. ober die Innervation der pia mater und des Plexus choroideus des’ Menschen. 2. Ges. Amt. 63: 562-575, 1922. 34. TRAYSTMAN, R. J., AND C. E. RAPELA. Effect of sympathetic nerve stimulation on cerebral and cephalic blood flow in dogs. Circulation Res. 36: 620-630, 1975.
Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (149.171.067.148) on January 1, 2019.
OF
hYt3IOLAXY
1976.
Printed
in U.SA.
Hypothalamic and thalamic blood flow during afferent stimulation in dogs PETER
SANDOR, IVAN T. DEMCHENKO, ARISZTID MOSKALENKO Experimental Research Department, Semmelweis Medical
SANDOR, PETER, IVAN T. DEMCHENKO, ARISZTID G. B. KOVACH, AND YURIJ E. MOSKALENKO. Hypothalamic and thalamic blood flow during somatic afferent stimulation in dogs. Am. J. Physiol. 231(l): 270-274. 1976. -The effect of somatic afferent C fiber stimulation on regional cerebral blood flow (rCBF) and cerebral tissue available oxygen (a@) was studied in 20 dogs under chloralose anesthesia. Mean arterial blood before and pressure, arterial Pco2, and pH were stabilized during the 3-min stimulation of the sciatic nerves (20 V, 300 ms, 15 Hz). Combined gold +platinum electrodes were chronically implanted into the ventral posterolateral nucleus of the thalamus, ventromedial nucleus of the hypothalamus, and into the white matter. Tissue aOz and rCBF of these regions were measured polarographically, the latter by the Hz-gas clearance technique. Blood flow changed from 42 5 2.1 to 28 t 1.7 ml/100 g per min (cerebrovascular resistance (CVR), from 2.9! t 0.29 to 4.31 -e 0.52 resistance units (RU) in the thalamus, corn 59 t, 5.0 to 47 2 5.0 ml1100 g per min (CVR: from 2.46 t 0.28 to 2.92 +: 0.35 RU) in the hypothalamus, and from 21 t 1.0 to 17 t, 0.8 ml/l00 g per min (CVR: from 6.367 t 0.35 to 7.672 t 0.40 RU) in the awhite matter during ipsilateral stimulation. Contralateral stimulation of the sciatic nerves caused a more moderate but likewise significant drop in rCBF and an increase in CVR except in the white matter. Parallel to these changes, tissue a0, decreased by 25 t, 2% in the thalamic and by 19 2 2% in the hypothalamic area, relative to the prestimulation level. rCBF; neural
control;
G. B. KOVACH, University,
AND
somatic
YURIJ
1082, Budapest,
E.
Hungary
nerve stimulation results in functional changes, as well, i.e., a specific type of evoked potentials can be recorded in the hypothalamus as shown by Dora et al. (8). In spite of these data, one of the most important questions is still open: does the anatomically abundant innervation of the dural and pial vessels and of the intracerebral arterioles have any functional role in the resting tone of the cerebrovascular smooth muscle and in autoregulation of the CBF? In addition to the inherent theoretical difficulties of this question, several methodological considerations present a problem. Thus, there are a great number of contradictory data concerning the effect of nerve stimulation on CBF. The current controversy over sympathetic cerebral vasoconstriction, for instance, is well characterised by the papers of D’Alecy and Feigl(6) and Traystman and Rapela (34). The disagreement may be due in part to the fact that a considerable number of the studies were performed under conditions in which either cerebral perfusion pressure (i.e., MABP) or arterial Pco2 was not controlled. Changes in these parameters occurred during stimulation, and the results are therefore misleading. Any increase in arterial pressure or in arterial Pcoll value can decrease or even totally obscure any vasoconstrictor effect of the stimulation. The aim of our present work was to study the effect of nociceptive somatic afferent stimulation on the local thalamic and hypothalamic blood flow and tissue available oxygen (aO,> in dogs at constant arterial blood pressure, Pco~, and pH.
tissue a0,; Hz-gas clearance
SINCE THE CLASSIC STUDIES of Nothnagel
and Hurtle (13, 27) in the last century and Chorobski and Penfield (4) in the early 1930’s, an increasing number of studies have demonstrated both sympathetic (1, 5, 9, 14, 20, 24, 26, 29-31, 33) and parasympathetic (12, 17, 18, 23, 25, 28) mechanisms involved in cerebrovascular control. Kovach et al. (16) in 1954 showed that in cross-circulation experiments, in which the brain of the recipient dog was hemodynamically isolated from the trunk and perfused by a donor dog, epinephrine or norepinephrine injection to the recipient’s trunk caused a significant increase in its total cerebral blood flow. The effect of somatic afferent impulses in the regulation of CBF has been much less studied than the role of the vegetative nerves. According to some recent data (Salford (32), Matrosov (22)), somatic tierent stimulation causes significant changes in the distribution of the lactate and catecholamine content of the brain. In addition to the changes in the chemical composition, sciatic
METHODS
The experiments were performed on 20 dogs of both sexes weighing 8-13 kg, anesthetized with 100 mg/kg iv of chloralosel; 4-6 days before the experiments combined platinum + gold electrodes were implanted according to Lim, Liu, and Moffit’s stereotaxic atlas (19) into the ventral posterolateral nucleus of the thalamus (R:18, L:8, V:16 mm) and into the ventromedial nucleus of the hypothalamus (R:19, L:2, V:6 mm) in order to determine regional blood flow and tissue a0, in these areas. The diameter of the double electrode was 200 Frn, and it was insulated with Araldite* or Teflon? The length of the 1 cr-o/+/-gluco-chloralose, E. Merck AG, Darmstadt, West Germany. * Araldite, CIBA (A. R. L.) Ltd. Duxford, Cambridge, England. 3 Medwire Corp., Mt. Vernon, N.Y. 97n
Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (149.171.067.148) on January 1, 2019.
EFFECT
OF
SOMATIC
AFFERENT
STIMULATION
ON
RCBF
AND
TISSUE
271
A@
active surface of the electrode tip was 1.5 mm. Both min. Since arterial blood pressure was kept constant tissue a0, and regional cerebral blood flow measure- and showed practically no change, reduced blood flow ments were performed polarographically, the latter in- must be a consequence of the marked 48% increase in termittently, by using Aukland’s (2) hydrogen-gas peripheral vascular resistance in this area. clearance technique and recorded on Kipp BD-5 microContralateral stimulation gave rise to a similar but graphs (Kipp and Zonen, DelR, Holland). Tissue a0, somewhat more moderate effect. The 27% decrease in changes were measured continuously and were ex- thalamic blood flow was associated with a 40% increase pressed in percentage changes relative to the prestimuin cerebrovascular resistance. The changes in CVR and lation level (100%). A zero a0, value was obtained after regional CBF were significant, whereas MABP, arterial stopping the heart with KC1 and switching the respiraPcop, and pH showed no significant alterations. tor off at the end of the experiments. Cerebral blood flow Hypothalamic blood flow changes. Cerebrovascular values were calculated by the 2-min initial slope tech- resistance in the ventromedial hypothalamic area rose nique and were expressed in milliliters per 100 g per by 22% under the effect of ipsilateral and by 23% under minute. Cerebrovascular resistance (CVR) was ex- that of contralateral somatic afferent stimulation (Tapressed in resistance units (RU) and calculated as fol- ble 2). Hypothalamic blood flow decreased by 18% in both cases (control values: 59 t 5.0, respectively, 80 t lows: CVRF=MABP mmHg/flow ml per 100 g per min. The mean arterial blood pressure (MABP) value used in 7.0 ml/100 g per min). These changes are statistically this calculation was determined in the middle of the 2.0- significant. At the same time the controlled parameters min initial slope, period. (MABP, arterial Pcoz, and pH) remained unaltered. Sciatic nerves were prepared on both sides in order to stimulate somatic afferent C fibers. The nerve was TABLE 1. Effect of ipsi- and contralateral sciatic slightly elevated by the stimulating electrode and was nerve stimulation on thalamic blood flow and vascular resistance in MABP, arterial electrically isolated from its surrounding with a paraffin oil pool. The parameters of stimulation were 20 V, Pco~, and arterial pH-stabilized dogs 300 ms, 15 Hz for 3 min (S 44 stimulator, Grass InstruNo. Side of ment Co., Quincy, Mass.). Arterial blood pressure was Parameter Before Stim. j During Stim. IYtFz of P Stimulation 3tim stabilized with an Engelking and Willig’s (10) modified buffer reservoir system and was monitored on a polyIpsiMABP, mmHg 1222 13 I 11329 I -7 7 BO.4 lateral Flow, ml/100 g 4222.1 28tl.7 -33 7 co.001 graph (Visiograph, Alvar Electronics, Paris). Heparin4 per min was given intravenously in a dose of 500 IU/kg. In order CVR, RU 2.91kO.29 4.31k0.52 +48 co.001 to stabilize arterial blood Pco? and pH levels, the dogs Arterial Pco2, 3721.1 36k1.3 -2 >0.3 were immobilized with Flaxedy15 (2 mg/kg iv), and the mmHg I I rate and volume of artificial respiration (Harvard dual Arterial pH 7.27kO.03 7.26kO.03 0 >0.2 phase control pump, Harvard Apparatus Co., Millis, MABP, mmHg 12627 12326 -2 >0.3 Mass. > were adjusted according to changes of the Pco2 Contralateral Flow, ml/100 g 48k6.1 3422.8 -27 co.01 level in the expired air, measured conti nuously by per min means of an infrared gas analyzer (Godart-Statham CVR, RU 2.859kO.36 3.81320.39 +40 0.9 co.001
7.67220.40 35kl.l
+24 -3
26 18
co.01 BO.4
24
>0.5
+2 +5
13 13
BO.1 >0.9
) -8 -5
13 18
>0.7 >0.3
9
>0.7
7.3hO.02 12427 i3k2.3 5.246k0.58 3521.7 7.32kO.01
0
0
tissue 120
DEMCHENKO,
KOVACH,
AND
MOSKALENKO
a02 %
1 cqntfalateral
III
time in see
1111
0 6 12
30
11 45
60
11
I
I1
L A TI 0 N
FIG. 1. Effect of ipsilateral and contralateral lation on thalamic tissue a0, (12 ipsilateral stimulation in 7 dogs). a02
I
90 105 120 135 150 165 180 195 205
75
W’t’MLJ
tissue no
1
-
sciatic nerve stimuand 10 contralateral
Z
1T
110
90
80
time in stc
lrrI1111 0 6 12
30
45
60
75
SO
I1 105
111111
120 135 150 165 180 1%
205
STIMULATION FIG. 2. Effect of ipsilateral lation on hypothalamic tissue stimulation in 5 dogs).
and contralateral a0, (12 ipsilateral
sciatic nerve stimuand 10 contralateral
DISCUSSION
Regional cerebral blood flow changes were studied in the VPL nucleus thalami and in the ventromedial nucleus of the hypothalamus. Changes in these regions were compared to those in the white matter. These regions were chosen for study because they play an important role either as relay stations for afferent neural impulses or as centers controlling specific cardiovascular functions. The parameters of prolonged sciatic nerve stimulation were the same as those used by Evans (11): According to his data, one can stimulate in this way, with careful preparation, the somatic afferent C fibers carrying nociceptive impulses to the CNS. One can presume that if C fiber stimulation causes changes in the regional distribution of cerebral blood flow, this can also happen in pathologic conditions under which somatic afferentation is increased in painful injuries. According to the above results, local peripheral resistance increased and local bloodsflow\ decreased in each
Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (149.171.067.148) on January 1, 2019.
EFFECT
OF
SOMATIC
AFFERENT
STIMULATION
ON
RCBF
area studied under the influence of prolonged ipsilateral sciatic nerve stimulation. Blood flow decreased more in the thalamic than in the hypothalamic area, and the smallest changes were observed in the white matter. It should be emphasized that the results presented here were obtained in dogs whose blood pressure, arterial Pcop, and pH were controlled. In some experiments the continuous control of these parameters temporarily failed. In these cases a marked increase in rCBF and tissue a0, was noted simultaneously with a significant elevation of mean arterial pressure during stimulation in each region studied. This observation supports our opinion and that of others (James, Millar, and Purves (15)) that it is of great importance to have a steady state with respect ‘to blood gas tensions and mean arterial pressure in studies of neurogenic control. Since neither local arterial nor local venous pressure was recorded in the experiments, it was not possible to calculate the absolute perfusion pressure values. Nevertheless, one can get a reasonable estimate of the relative changes in regional cerebrovascular resistance by calculating the MABP/rCBF r:ltio. The control flow values obtained in our experiments are in good accordance with the average “resting” flow values of the grey and white matter in anesthetized dogs, reported by Lubbers (21). However, there was a considerable difference between the control hypothalamic flow values measured in the ipsilaterally and contralaterally stimulated groups (Table 2). Mean arterial blood pressure was about the same in both experimental groups (138 and 131 mmHg), but in the contralaterally stimulated group we measured high hypotha-
AND
TISSUE
273
Ao2
lamic control blood flow values in 3 out of 10 cases (84, 87, and 77 ml/l00 g per min, in 2 animals). This may be the reason for the relatively high resting flow value of this group. In four experiments, 5 mg/kg of phenoxyben.zamine6 were administered intravenously to the dogs in the second phase of the study, and sciatic nerve stimulation was repeated after 30 min. MABP decreased to about 70-80 mmHg, rCBF and blood gas values were unchanged after administration of phenoxybenzamine, and sciatic nerve stimulation caused no rCBF changes in any of the cerebral regions studied (7). Tissue a0, decreased both in the thalamic and in the hypothalamic region during somatic afferent stimulation. As in the case of local blood flow changes, ipsilatera1 stimulation was more effective than contralateral. According to our data, the amplitude of a0, oscillations in brain tissue decreases significantly during somatic afferent stimulation, whereas frequency remains unchanged. These changes are presented and discussed in detail in another paper (7). Our results corroborate the view of Burgess (3) that oxygen cycles are not random and independent but that they are coupled from some central source. This work was supported in part by National Institute of Neurological Diseases and Stroke Grant NS 10939-01. Current address of I. T. Demchenko and Y. E. Moskalenko: Cerebrovascular Research Laboratory, Sechenov Institute of Evolutionary Physiology and Biochemistry, Union of Soviet Socialist Republics Academy of Sciences, Leningrad, U.S.S.R. Received
for publication
28 July
1975.
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