Upsala J M e d Sci 92: 185-192, 1987 The Influence of Bilateral Electrical Preganglionic Sympathetic Stimulation on Intra- and Extracranial Blood Flow Lars-Owe D. Koskinen Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Uppsala, Sweden ABSTRACT The e f f e c t s o f b i l a t e r a l e l e c t r i c a l stimulation (SS) o f t h e c e r v i c a l sympathetic chain on i n t r a - and e x t r a cerebral blood flows were studied w i t h t h e labelled microsphere method in t h e rabbit. C o n t r o l blood f l o w was determined before the SS was started. The stimulation frequency was 7 Hz, t h e impulse duration 2 ms, t h e intensity 7 V and t h e stimulation t i m e varied between 1 t o 5 minutes before t h e second blood f l o w determination. A r t e r i a l blood gas values and blood pressure were unaffected by t h e stimulation. Due t o the SS there were blood flow decrements in the extracranial tissues between 60-96%. The blood flow in t h e eyes, the dura, pineal gland and choroid plexa was markedly reduced during the 55. N o obvious e f f e c t was e l i c i t e d by t h e SS in t h e regional or t o t a l cerebral blood flow. The stimulation t o c o n t r o l blood f l o w r a t i o ranged between 0.92 f 0.08 t o 1.13 2 0.09 in d i f f e r e n t p a r t s o f t h e brain. The conclusions are t h a t SS e l i c i t s vasoconstriction in several extra- and intracranial nonneuronal tissues and in the eye. Cerebral blood f l o w i s n o t influenced b y the SS. INTRODUCTION The cerebral vasculature is innervated by several types o f nerves, p a r t i c u l a r l y b y sympathetic nerve fibres emanating f r o m t h e superior c e r v i c a l ganglion. The influence o f these sympathetic nerves on cerebral blood f l o w has been evaluated i n several species and under a variety o f conditions and w i t h c o n f l i c t i n g results ( 9 , 17, 19). In t h e conscious and anaesthetized r a b b i t a t i t s normal blood pressure no obvious tonic influence o f the cervical sympathetic nerves was detected on regional (rCBF) and t o t a l (CBFtot) cerebral blood flow, b u t on extracranial blood flows (10-13). The e l e c t r i c a l stimulation o f t h e sympathetic chain unilaterally did n o t markedly influence t h e cerebral blood flow in t h e normotensive c a t ( 3 ) , monkey (1) and r a b b i t (5, 15). In acute hypertension, on t h e other hand, sympathetic stimulation has a clear protective effect, preventing cerebral hyperemia and disruption o f the blood-brain-barrier (4, 8). Indeed, in t h e normotensive 185 . . animal an "escape phenomenon" f r o m the sympathetic influence on the cerebral vessels has been proposed. Thus, in the r a b b i t a decrease i n CBF was shown early in the course o f stimulation o f the c e r v i c a l sympathetic chain (18) while Beausang-Linder BC H u l t c r a n t z (5) found no such effect. It has been speculated that, due t o a double (ipsi and contralateral cervical sympathetic) innervation o f the cerebral vessels a more pronounced e f f e c t could be e l i c i t e d by bilateral stimulation. Indeed, it was recently reported by Busija (6, 7) t h a t the bilateral, but not unilateral, stimulation of t h e c e r v i c a l sympathetic ganglion a t 8 and 16 H z considerably reduced the cerebral blood f l o w i n t h e rabbit. The present investigation was undertaken in order t o elucidate whether 1) b i l a t e r a l preganglionic cervical sympathetic stimulation a t a frequency regarded as being t h e upper p a r t of the physiological range influences r C B F and C B F t o t and 2) whether nonneural intracranial tissues are a f f e c t e d by the stimulation and 3) t o what extent ocular and extracranial tissues are affected. METHODS Seven New Zealand albino rabbits of either sex weighing between 1.7-4.0 k g were used. The animal was anesthetized w i t h a 25 % solution o f urethane i.v. in a dose o f 7 ml k g - l b.w. The animal was tracheotomized and ventilated by a Palmer pump. Mean a r t e r i a l blood pressure (MAP) measurements, w i t h a Druck PDCR 75/1 transducer and an Servogor 460 recorder, and blood sampling was conducted f r o m a pair of cannulated arteries. The regional blood f l o w was measured by the labelled microsphere method (2, 20). Microspheres were injected d i r e c t l y i n t o the l e f t ventricle through a cannula introduced retrogradely via the l e f t brachial artery. Spheres, 15 um in diameter (NEN, Boston, Massachusetts, USA), labelled w i t h 95 Nb, Io3 R u and 141 Ce were used . One femoral vein was cannulated and used f o r drug injections. The cervical sympathetic chain was bilaterally i d e n t i f i e d and sectioned about one centimeter below the upper c e r v i c a l ganglion. The distal p a r t of t h e sympathetic nerve was b i l a t e r a l l y isolated, covered w i t h mineral oil, and electrically stimulated w i t h bipolar silver electrodes. C a r e was taken not t o stimulate the aortic depressor nerve. The stimulator (Digitimer DSSA, Welwyn Garden C i t y , England) was operated a t a stimulatory frequency o f 7 Hz, intensity 7 V and impulse duration 2 ms. The f i r s t microsphere i n j e c t i o n was performed under resting conditions. The nerve was then bilaterally stimulated f o r 3 t o 5 m i n (in one case 1 min) before, during and 1 m i n a f t e r the second microsphere injection. A r t e r i a l blood gases (Pa02 and PaC02) and p H were measured a t intervals w i t h an ABL2 acid-base analyzer (Radiometer, Copenhagen, Denmark). If needed, sodium bicarbonate was given i.v. t o c o r r e c t deviations i n pH. Pancuronium bromide (PavulonR, Organon, Oss, Holland) was administered in a dose o f 0.05-0.2 mg/kg in order t o induce 186 skeletal muscle relaxation. The body temperature was recorded by a r e c t a l thermistor and maintained a t about 38-39OC w i t h a heating pad. Heparin, 500 I U / k g b.w. was used as anticoagulant. A f t e r the experiment t h e animal was sacrificed by an i.v. i n j e c t i o n o f saturated KCI. Organs and tissue samples f r o m organs were excised and placed in preweighed plastic tubes. Gray m a t t e r f r o m the f r o n t a l and o c c i p i t a l cortex, hippocampal region, caudate nucleus, thalamic region, hypothalamic region, collicule, pons-mesencephalon, medulla oblongata, cerebellum and spinal cord were excised. T o t a l CBF was calculated as including a l l regions except the medulla oblongata, cerebellum and spinal cord. The eye was dissected i n t o t h e retina, choroid, i r i s and c i l i a r y processes. Various other tissues were also sampled. The r a d i o a c t i v i t y o f blood and tissue samples was determined b y gamma spectrometry. Blood flows were calculated according t o t h e free flow method (2). A l l results are presented as means 2 SEM. Statistical evaluations o f the means was performed w i t h t h e two-tailed Student' s t - t e s t f o r paired observations. RESULTS In t h e c o n t r o l situation the cardiovascular variables were w i t h i n the normal range, and d i d n o t change during nerve stirnulation (Table 1). Mydriasis was observed on b o t h sides during the stimulation. There was no difference i n blood f l o w between t h e t w o sides, and t h e duration o f stimulation did n o t influence t h e response. Therefore pooled data were used in t h e calculations o f means. Table 1 A r t e r i a l blood gases, p H and MAP before and during b i l a t e r a l c e r v i c a l sympathetic stimulation. Pressures are expressed in kPa. Mean i SEM. Control Stimulation MAP PHa 11.0 2 0.7 13.7 ? 0.7 4.2 ? 0.2 7.44 i 0.02 11.0 2 0.9 13.8 2 0.8 4.3 t 0.1 7.42 i 0.02 As shown in F i g u r e 1, b i l a t e r a l sympathetic stimulation caused blood f l o w decrements between 60 and 96 % in some extracranial tissues. The most r e a c t i v e tissues were t h e masseter muscle (p