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The effect of sympathetic stimulation on blood flow through the uvea, retina and optic nerve in monkeys (Macaca irus)
Exp. Eye Res. (1977) 25, 19-24
The Effect of Sympathetic Stimulation on Blood Flow through the Uvea, Retina and Optic Nerve in Monkeys (Macaca hw) ALIJERT
University
ALM
Eye Clinic cwd Department of Physiology and Medical University of Vppsaln, Uppsala: Xweden
Biopiiysics,
(Received 18 March 1.976 and in revised form 22 October 1976, London) Tntraeardiac injections of 15 pm labelled microspheres were used to determine ocular blood flow in monkeys during unilateral stimulation of the cervical sympathetic chain. Before stimulation both cervical sympathetic chains were cut, and the distal end of one side was stimulated. In nine animals stimulation at 10 Hz for one min significantly reduced blood flow through iris, ciliary muscle and choroid by 52, 29 and 30”/0 respectively by comparisons with the sympathectomized control tissues. Blood flow reductions of 23 and 527; also occurred in ciliary processes and anterior sclera, while no significant changes were observed for blood flow through retina, optic nerve head or retrobulbar part of bhe optic nerve. Key zoords: sympathetic stimulation; labelled microspheres; ocular blood flow; retina; iris; ciliary body; choroid; optic nerve; monkeys.
1. Introduction In a previous study it was found that sympathetic stinmlation reduced blood flow through the various parts of the uvea in cats, while there were no consistent changes in retinal blood flow (Alm and Bill, 1973a). Blood flow was determined by mea,ns of radioactively labelled microspheres. The present study was undertaken to determine whether stimulation of the cervical sympathetic chain causes similar changes in ocular blood flow in monkeys. Attempts were made to determine blood flow through various parts of the optic nerve as well as through the retina and the different parts of the uvea. Blood flow values for brain and some other tissues were also calculated and have been presented elsewhere (Alm, 1975).
2. Methods Nine cynomolgus monkeys (J~a~accc~PU) of either sex weighing between 2.3 and 3.1 kg were used. Sodium methohexital, 50-100 mg i.m. (Brietal Sodjum@, Lilly) was used to induce anesthesia,, which was maintained by i.v. injections of pentobarbitxl sodium (Penthotalsodium@, Abbott). The animals were traeheotomized and artificially ventilated. Mean arterial blood pressure was measured, and the adequacy of the ventilation was controlled by determinations of a.rterial Paz, PC0 and pH. Both cervica’l sympathetic chains were cut and a bipolar platinum electrod?e with an interelectrode distance of I mm, connected to a stimulator, AEL model 111 (American Electronic Laboratories), was used to stimulate the distal end of one of the sympathetic chains. Squa,re-wave pulses at 10 Hz were used, the duration was 1 msec and the stimulation intensity 6-8 V which was above the level causing maximal pupillary dilatation. Blood flow determinations lvere made bv means of the labelled microsphere method after 1 min of continuous stimulation. The lahelled mioi~osphere method When injected into the left ventricle of the heart the radioactively labelled microspheres become mixed with arterial blood and follow the blood strea,m t’o the various organs in proportion to blood flow. Since, as a rule, only a negligible number escape through the 19
20
A, ALX
capillary bed they act as a non-recirculating blood flow indicator. Thus blood flow to various tissues can be calculated if the radioactivity of a known reference blood flow is determined. In the present study 2-O ml of a 5% suspension of 1515 pm microspheres labelled with lesYb (3 M Company, St. Paul, Minnesota) were injected. The specifio a.ctivity was 1 mCi/g. The reference flow was obtained from a cannulated femoral artery, where blood was sampled during 2 nun starting at the time of the microsphere injection. At the end of this period the animals were killed by i.v. injections of KC1 and dissected. Eoth eyes were enucleated and dissected as previously described (Alm and Bill, 1972, 1973b). Separate samples were obtained of the optic nerve, including the nerve head, the iris a,nd the ciliary body, and flat mount preparations were made of the choroid and the retina. Samples were also taken from the anterior sclera. Samples of ciliary muscle and ciliary processes were obtained by dissecting the ciliary body under a microscope after glutaraldehyde fixation and dehydration. The flat mount preparations of choroid and retina permitted determinations of blood flow per area for various regions of these tissues, as well as total blood flow per tissue sample. The optic nerve was slioed as preto its long axis. The five viously described (Alm and Bill, 19’73b) a1most perpendicularly most distal slices, including the nerve head, were about 200 pm thick and the remaining three to five slices about 500 pm. Reference blood and tissue samples were weighed, with the exception of the flat mount preparations. The radioactivity was determined by gamma spectrometry. Blood flow estimates were then obtained by dividing the activity of the tissue sample by the activity per mg blood flow per min calculated for the reference flow. Samples were also taken from various pieces of the brain, from parotid gland, masseter muscle, tongue, cardiac muscle, lungs and some abdominal organs. These data as well as data for arterial blood pressure, PO*, Pcoz and pH and further details of the procedures have already been published (Alm, 1975).
3. Results Table I presents the blood Bow values for the retina, the various parts of the uvea and the anterior sclera on the sympathectomized, control side as well as the blood TABLE
I
Blood Jlow through sympathectomized side, percent reductio+a of blood jZow on stimulated side and siqni$cance levek (Student’s t-test, paired data). Meanfs.E., n = 9
Tissue
Retina Iris Ciliary body Choroid Ciliary processes Ciliary muscle Anterior sclera
Blood flow in whole tissue (mg/min) (sympathectomized side)
Blood flow (g/min/lOO g tissue) (sympathectomized side)
33&Z 4&l 79*4 55s*59
Percent reduction of blood flow on stimulated side
Significance level
w.3 52&7 22&3 30&6
P
120*15
23f8
P
176+10
29+5 52&21
P
Et1
P
The weights for the ciliary processes and muscle are calculated from the dry weight on the assumption that dry weight/wet weight ratio is 0.20 (see Alm and Bill, 1972).
SYMPATHETIC
STIMULATION
A?SD OCULAR
BLOOD
21
FLOW
flow reduction found on the stimulated side. No significant reduction in retinal blood flow was found, while blood %ow through the various parts of the uvea was significantly reduced, with the ciliary processes as a possible exception. A possibly significant reduction was also found for the anterior &era. Calculations of blood %ow per area for various regions of the choroid and the retina did not reveal any significant regional differences in blood flow response to sympathetic stimulation. Figure 1 shows the blood %ow calculated for the various slices of the optic nerve for control side and stimulated side. For the control side, blood %ow through slice 1
0
200
400
600
800
1000
1500 Distance
from
2000 nerve
head
2500 surface
3000
3500
(pm)
FIG. 1. l\Iean values and standard error of blood flow through slices cut perpendicularly to the length axis of the optic nerve. The five most distal slices were about 200 pm thick. the remaining slices about 500 Pm. The most distal slice included the optic nerve head. The seven first slices were obtained from nine animals while slices S-10 represent the means of at least five monkeys. (--) Control eye; (- - -) experimental eye.
was signifkantly Iarger than that through slice 2 and slices 4-8 (P < 0.01 or smaller), and the differences between slice 1 and slices 9 and 10 were possibly significant (P < O.oZ5). There was, however, no significant difference between the two sides either for blood %ow calculated for each pair of slices of for the calculated mean %ow for the whole optic nerve. 4. Discussion The number of spheres injected in the present study wa*sthe same as used in previously reported experiments (Alm and Bill, 197313) and, as discussed then, such a large dose is necessary only if attempts are made to determine blood %ow through very small pieces of tissue, such as the optic nerve head. As in previous experiments the dose caused a moderate increase in blood pressure, in the order of lo-20 cm H,Q, when injected. It was assumed that such changes in the general circulation did not invalidate comparisons between the two eyes. In the present study both cervical sympathetic chains were cut in order to ensure that no basal sympathetic tone existed on the control side: which might conceal the effects of sympathetic stimulation. The effect of the sympathectomy on blood %ow through the control tissues was not determined. In tissues where sympathetic tone causes vasoconstriction acute sympathectomy may be expected to cause a.n increased blood %ow in proportion to actual sympathetic tone.
32
a. AI,31
Uvea
Stimulation of the cervical sympathetic chain is known to cause marked reductions in blood flow through the various parts of the uvea in cats (Alm and Bill: 1973a). In the present study significant blood flow reductions were observed in all regions, with the possible exception of the ciliary processes. The percentage reductions for blood flow in iris, choroid, ciliary processes and ciliary muscle were 52, 30, 23 and 29% respectively. In the case of the choroid and ciliary processes the reductions were smaller than those previously reported in similar experiments on cats (Aim and Bill, 1973a). Retina
The retina is supplied with blood from the central retinal artery. The extraocular part of this artery is innervated by the sympathetic nervous system but no adrenergic nerves have been found distal to the lamina eribrosa (Ehinger, 1966; Laties and Jacobowitz, 1966). Thus sympathetic stimulation cannot be expected to have an effect on the intraretinal part of the vascular bed, but a constriction may take place in retinal arteries proximal to lamina cribrosa. This would cause an increased pressure fall in the arteries leading to the retina and consequently a reduced perfusion pressure (defined as the mean arterial pressure in the arteries entering the retina less the pressure in the veins leaving the eye). In a previous study in cats, extrabulbar vasoconstriction seemed to affect retinal blood flow, as reflected by a fall in the oxygen tension in the vitreous body close to the retina (Alm and Bill, 1973a). However, quantitative determinations with labelled microspheres in the same study did not show reduced retinal blood flow at stimulation frequencies that reduced vitreous oxygen tension. Thus, in cats, even if a redistribution of blood flow may have taken place within the retina it was assumed that sympathetic stimulation had no consistent effect on total retinal blood flow. The present study indicates that in monkeys the effect of sympathetic stimulation on total retinal blood flow is also very small, and suggests that any reduction in retinal perfusion pressure is compensated by vasodilatation in the intraretinal vascular bed. Efficient autoregulation of retinal blood flow has been observed both in cats (Alm and Bill, 1972) and monkeys (Alm and Bill, 197310). Contrary to these results Weiter, Schachar and Ernest (1973) reported marked reductions of about 40%, in retinal blood flow in three cats when the cervical sympathetic chain was stimulated. A possible explanation for the difference in results is the sphere sizes used in the two studies. Weiter, Schachar and Ernest used spheres with a mean diameter of 50 pm. In cats the retina is supplied by three or more small arteries which, as they enter the eye, has a diameter of 35-50 pm (Porsaa, 1941). Thus there must be a certain risk that at least one of these arteries is closed by entrapment of a large sphere prior to lamina cribrosa, which would result in too low a flow value for the retina. This risk must increase considerably if the extrabulbar part of the retinal vessels is constricted. Another disadvantage in using large spheres is the limited number that can be safely injected. The sensitivity of the method depends on the number of spheres in the sample (Buckberg et al.: 1971) and it can be calculated that in the study of Weiter et al. (1973) less than 30 spheres reached each retina. The fact that these investigators used so few spheres and only performed three experiments makes a 40% reduction of questionable statistical significance.
SYMPATHETIC
STIMULATION
AFD
OCULAR
BLOOD
FLOW
23
Optic nerve
The retrobulbar part of the optic nerve (OK) is suppliecl with blood from sereval aourees. Thus the centre of t,he nerve may receive centrifugal branches from the central retinal artery, and there is always a centripetal vascular system of pial branches derived from the central retinal artery or the ophthalmic artery and also recurrem pial branches from the peripapillary choroidal vessels (see Hayreh, 1970). The extraneural parts of these vessels are supplied by the sympathetic nervous system but the degree of innervation of the intraneural parts is less clear. Vascular adrenergic nerves; unrelated to the central retinal artery, have been observed within the ON (Ehinger, pers. comm.) but the ratio innervated/non-innervated vessels is unknown as is the physiological significance of these nerves. In the present study sympathetic stimulation had no significant effect on blood flow through the ON and it seems likely that the lack of blood flow reduction in the present study was due either to an inadequate innerva,tion of distal parts of the resistance vessels, which may then respond to a proximal sympathetic vasoconstriction with a compensatory vasodilatation, or to prevention of sympathetic vasoconst’riction in crucial parts of the vascular bed ?~y some unknown metabolic factor. Both these explanations suggest autoregulation of ON blood flow.
In the present study no significant reduction was observed on the stimulated sick. Although a very large dose of spheres was used very few were trapped within the optic nerve head (ONH) and the variability of the blood flow values was considerable. (The 95% confidence interval for the mean effect on ONH blood flow of sympathetic Aimulation was from a 52% increase to a 66% reduction.) Thus it seems clear that stimulation of the cervical sympathetic chain in monkeys influences blood flow differently in the various vascular beds of the eye. Significant blood flow reductions of various degrees were observed for the different parts of the uvea while no effects on blood flow through retina and ON w&s observed. The error for ONH blood flow determinations was too large to permit any conclusions regarding the effect of sympathetic tone on ONH blood flow. ACKNOWLEDGMENTS
This work was supported by PHS grant EY 00475 from the Kational Eye Institute and by a grant B74-14X-147 from the Swedish 3Iedical Research Council. The author thanks Professor Anders Bill for valuable discussions during the experiments and the preparation of the manuscript, and Miss Monica Thor&r and Nrs Anita Gstberg for skilful technical a.ssistance. REFERENCES
Aim, 3. (1975). The effect of stimulation of the cervical sympat’hetic chain on regional cerebral blood flow in monkeys. Acta Physiol. &and. 93, 483-9. A. and Bill, A. (1972). The oxygen supply to t,he retina, II. Effects of high intraocular pressure and of increased arterial carbon dioxide tension on weal and retinal blood flow in cats. Acta Physiol. Xcand. 84, 306-19. Aim, B. and Bill, A. (1973a). The effect of stimulation of the cervical sympathetic chain on retinal oxygen tension and on uveal, retinal and cerebral blood flow in cats. Acta Physiol. &and. 88,84-94. Xlm,
24
9. ALM
Alm, 8. and Bill, A. (197313). Ocular and optic nerve blood flow at normal and increased intraocular pressures in monkeys (Macaca irus) : a study with radioactively labelled microspheres including flow determinations in brain and some other tissues. Eqn. Eye Rex. 15, 15-29. Buckberg, G. D., Luck, J. C., Payne, D. B., Hoffman, J. I. E., Archie, J. P. and Fixler, D. E. (1971). Some sources of error in measuring regional blood flow with radioaetive microspheres. J. Appl. Physiol. 31, 598-604. Ehinger, B. (1966). Adrenergic nerves t.o t,he eye and to related structures in man and in the cynomolgus monkey (Macaca irus). Exp. Eye Res. 5, 42-52. Hayreh, S. S. (1970). Pathogenesis of visual field defects. Rr. J. Ophthalmol. 54, 289-311. Laties, A. RI. and Jacobowitz, D. ,4. (1966). B comparative study of the autonomic innervation of the eye in monkey, cat and rabbit. Anat. Rec. 156,383-96. Porsaa, K. (1941). Experimental studies on the vasomotor innervation of the retinal arteries. Acta Ophthalmol. (Kbh). Suppl. 18. Weiter, J. J., Schachar, R. A. and Ernest, J. T. (1973). Control of intraocular b!ood flow. II Effects of sympathetic tone. Invest. Ophthalmol. 12, 3324.
The Effect of Sympathetic Stimulation on Blood Flow through the Uvea, Retina and Optic Nerve in Monkeys (Macaca hw) ALIJERT
University
ALM
Eye Clinic cwd Department of Physiology and Medical University of Vppsaln, Uppsala: Xweden
Biopiiysics,
(Received 18 March 1.976 and in revised form 22 October 1976, London) Tntraeardiac injections of 15 pm labelled microspheres were used to determine ocular blood flow in monkeys during unilateral stimulation of the cervical sympathetic chain. Before stimulation both cervical sympathetic chains were cut, and the distal end of one side was stimulated. In nine animals stimulation at 10 Hz for one min significantly reduced blood flow through iris, ciliary muscle and choroid by 52, 29 and 30”/0 respectively by comparisons with the sympathectomized control tissues. Blood flow reductions of 23 and 527; also occurred in ciliary processes and anterior sclera, while no significant changes were observed for blood flow through retina, optic nerve head or retrobulbar part of bhe optic nerve. Key zoords: sympathetic stimulation; labelled microspheres; ocular blood flow; retina; iris; ciliary body; choroid; optic nerve; monkeys.
1. Introduction In a previous study it was found that sympathetic stinmlation reduced blood flow through the various parts of the uvea in cats, while there were no consistent changes in retinal blood flow (Alm and Bill, 1973a). Blood flow was determined by mea,ns of radioactively labelled microspheres. The present study was undertaken to determine whether stimulation of the cervical sympathetic chain causes similar changes in ocular blood flow in monkeys. Attempts were made to determine blood flow through various parts of the optic nerve as well as through the retina and the different parts of the uvea. Blood flow values for brain and some other tissues were also calculated and have been presented elsewhere (Alm, 1975).
2. Methods Nine cynomolgus monkeys (J~a~accc~PU) of either sex weighing between 2.3 and 3.1 kg were used. Sodium methohexital, 50-100 mg i.m. (Brietal Sodjum@, Lilly) was used to induce anesthesia,, which was maintained by i.v. injections of pentobarbitxl sodium (Penthotalsodium@, Abbott). The animals were traeheotomized and artificially ventilated. Mean arterial blood pressure was measured, and the adequacy of the ventilation was controlled by determinations of a.rterial Paz, PC0 and pH. Both cervica’l sympathetic chains were cut and a bipolar platinum electrod?e with an interelectrode distance of I mm, connected to a stimulator, AEL model 111 (American Electronic Laboratories), was used to stimulate the distal end of one of the sympathetic chains. Squa,re-wave pulses at 10 Hz were used, the duration was 1 msec and the stimulation intensity 6-8 V which was above the level causing maximal pupillary dilatation. Blood flow determinations lvere made bv means of the labelled microsphere method after 1 min of continuous stimulation. The lahelled mioi~osphere method When injected into the left ventricle of the heart the radioactively labelled microspheres become mixed with arterial blood and follow the blood strea,m t’o the various organs in proportion to blood flow. Since, as a rule, only a negligible number escape through the 19
20
A, ALX
capillary bed they act as a non-recirculating blood flow indicator. Thus blood flow to various tissues can be calculated if the radioactivity of a known reference blood flow is determined. In the present study 2-O ml of a 5% suspension of 1515 pm microspheres labelled with lesYb (3 M Company, St. Paul, Minnesota) were injected. The specifio a.ctivity was 1 mCi/g. The reference flow was obtained from a cannulated femoral artery, where blood was sampled during 2 nun starting at the time of the microsphere injection. At the end of this period the animals were killed by i.v. injections of KC1 and dissected. Eoth eyes were enucleated and dissected as previously described (Alm and Bill, 1972, 1973b). Separate samples were obtained of the optic nerve, including the nerve head, the iris a,nd the ciliary body, and flat mount preparations were made of the choroid and the retina. Samples were also taken from the anterior sclera. Samples of ciliary muscle and ciliary processes were obtained by dissecting the ciliary body under a microscope after glutaraldehyde fixation and dehydration. The flat mount preparations of choroid and retina permitted determinations of blood flow per area for various regions of these tissues, as well as total blood flow per tissue sample. The optic nerve was slioed as preto its long axis. The five viously described (Alm and Bill, 19’73b) a1most perpendicularly most distal slices, including the nerve head, were about 200 pm thick and the remaining three to five slices about 500 pm. Reference blood and tissue samples were weighed, with the exception of the flat mount preparations. The radioactivity was determined by gamma spectrometry. Blood flow estimates were then obtained by dividing the activity of the tissue sample by the activity per mg blood flow per min calculated for the reference flow. Samples were also taken from various pieces of the brain, from parotid gland, masseter muscle, tongue, cardiac muscle, lungs and some abdominal organs. These data as well as data for arterial blood pressure, PO*, Pcoz and pH and further details of the procedures have already been published (Alm, 1975).
3. Results Table I presents the blood Bow values for the retina, the various parts of the uvea and the anterior sclera on the sympathectomized, control side as well as the blood TABLE
I
Blood Jlow through sympathectomized side, percent reductio+a of blood jZow on stimulated side and siqni$cance levek (Student’s t-test, paired data). Meanfs.E., n = 9
Tissue
Retina Iris Ciliary body Choroid Ciliary processes Ciliary muscle Anterior sclera
Blood flow in whole tissue (mg/min) (sympathectomized side)
Blood flow (g/min/lOO g tissue) (sympathectomized side)
33&Z 4&l 79*4 55s*59
Percent reduction of blood flow on stimulated side
Significance level
w.3 52&7 22&3 30&6
P
120*15
23f8
P
176+10
29+5 52&21
P
Et1
P
The weights for the ciliary processes and muscle are calculated from the dry weight on the assumption that dry weight/wet weight ratio is 0.20 (see Alm and Bill, 1972).
SYMPATHETIC
STIMULATION
A?SD OCULAR
BLOOD
21
FLOW
flow reduction found on the stimulated side. No significant reduction in retinal blood flow was found, while blood %ow through the various parts of the uvea was significantly reduced, with the ciliary processes as a possible exception. A possibly significant reduction was also found for the anterior &era. Calculations of blood %ow per area for various regions of the choroid and the retina did not reveal any significant regional differences in blood flow response to sympathetic stimulation. Figure 1 shows the blood %ow calculated for the various slices of the optic nerve for control side and stimulated side. For the control side, blood %ow through slice 1
0
200
400
600
800
1000
1500 Distance
from
2000 nerve
head
2500 surface
3000
3500
(pm)
FIG. 1. l\Iean values and standard error of blood flow through slices cut perpendicularly to the length axis of the optic nerve. The five most distal slices were about 200 pm thick. the remaining slices about 500 Pm. The most distal slice included the optic nerve head. The seven first slices were obtained from nine animals while slices S-10 represent the means of at least five monkeys. (--) Control eye; (- - -) experimental eye.
was signifkantly Iarger than that through slice 2 and slices 4-8 (P < 0.01 or smaller), and the differences between slice 1 and slices 9 and 10 were possibly significant (P < O.oZ5). There was, however, no significant difference between the two sides either for blood %ow calculated for each pair of slices of for the calculated mean %ow for the whole optic nerve. 4. Discussion The number of spheres injected in the present study wa*sthe same as used in previously reported experiments (Alm and Bill, 197313) and, as discussed then, such a large dose is necessary only if attempts are made to determine blood %ow through very small pieces of tissue, such as the optic nerve head. As in previous experiments the dose caused a moderate increase in blood pressure, in the order of lo-20 cm H,Q, when injected. It was assumed that such changes in the general circulation did not invalidate comparisons between the two eyes. In the present study both cervical sympathetic chains were cut in order to ensure that no basal sympathetic tone existed on the control side: which might conceal the effects of sympathetic stimulation. The effect of the sympathectomy on blood %ow through the control tissues was not determined. In tissues where sympathetic tone causes vasoconstriction acute sympathectomy may be expected to cause a.n increased blood %ow in proportion to actual sympathetic tone.
32
a. AI,31
Uvea
Stimulation of the cervical sympathetic chain is known to cause marked reductions in blood flow through the various parts of the uvea in cats (Alm and Bill: 1973a). In the present study significant blood flow reductions were observed in all regions, with the possible exception of the ciliary processes. The percentage reductions for blood flow in iris, choroid, ciliary processes and ciliary muscle were 52, 30, 23 and 29% respectively. In the case of the choroid and ciliary processes the reductions were smaller than those previously reported in similar experiments on cats (Aim and Bill, 1973a). Retina
The retina is supplied with blood from the central retinal artery. The extraocular part of this artery is innervated by the sympathetic nervous system but no adrenergic nerves have been found distal to the lamina eribrosa (Ehinger, 1966; Laties and Jacobowitz, 1966). Thus sympathetic stimulation cannot be expected to have an effect on the intraretinal part of the vascular bed, but a constriction may take place in retinal arteries proximal to lamina cribrosa. This would cause an increased pressure fall in the arteries leading to the retina and consequently a reduced perfusion pressure (defined as the mean arterial pressure in the arteries entering the retina less the pressure in the veins leaving the eye). In a previous study in cats, extrabulbar vasoconstriction seemed to affect retinal blood flow, as reflected by a fall in the oxygen tension in the vitreous body close to the retina (Alm and Bill, 1973a). However, quantitative determinations with labelled microspheres in the same study did not show reduced retinal blood flow at stimulation frequencies that reduced vitreous oxygen tension. Thus, in cats, even if a redistribution of blood flow may have taken place within the retina it was assumed that sympathetic stimulation had no consistent effect on total retinal blood flow. The present study indicates that in monkeys the effect of sympathetic stimulation on total retinal blood flow is also very small, and suggests that any reduction in retinal perfusion pressure is compensated by vasodilatation in the intraretinal vascular bed. Efficient autoregulation of retinal blood flow has been observed both in cats (Alm and Bill, 1972) and monkeys (Alm and Bill, 197310). Contrary to these results Weiter, Schachar and Ernest (1973) reported marked reductions of about 40%, in retinal blood flow in three cats when the cervical sympathetic chain was stimulated. A possible explanation for the difference in results is the sphere sizes used in the two studies. Weiter, Schachar and Ernest used spheres with a mean diameter of 50 pm. In cats the retina is supplied by three or more small arteries which, as they enter the eye, has a diameter of 35-50 pm (Porsaa, 1941). Thus there must be a certain risk that at least one of these arteries is closed by entrapment of a large sphere prior to lamina cribrosa, which would result in too low a flow value for the retina. This risk must increase considerably if the extrabulbar part of the retinal vessels is constricted. Another disadvantage in using large spheres is the limited number that can be safely injected. The sensitivity of the method depends on the number of spheres in the sample (Buckberg et al.: 1971) and it can be calculated that in the study of Weiter et al. (1973) less than 30 spheres reached each retina. The fact that these investigators used so few spheres and only performed three experiments makes a 40% reduction of questionable statistical significance.
SYMPATHETIC
STIMULATION
AFD
OCULAR
BLOOD
FLOW
23
Optic nerve
The retrobulbar part of the optic nerve (OK) is suppliecl with blood from sereval aourees. Thus the centre of t,he nerve may receive centrifugal branches from the central retinal artery, and there is always a centripetal vascular system of pial branches derived from the central retinal artery or the ophthalmic artery and also recurrem pial branches from the peripapillary choroidal vessels (see Hayreh, 1970). The extraneural parts of these vessels are supplied by the sympathetic nervous system but the degree of innervation of the intraneural parts is less clear. Vascular adrenergic nerves; unrelated to the central retinal artery, have been observed within the ON (Ehinger, pers. comm.) but the ratio innervated/non-innervated vessels is unknown as is the physiological significance of these nerves. In the present study sympathetic stimulation had no significant effect on blood flow through the ON and it seems likely that the lack of blood flow reduction in the present study was due either to an inadequate innerva,tion of distal parts of the resistance vessels, which may then respond to a proximal sympathetic vasoconstriction with a compensatory vasodilatation, or to prevention of sympathetic vasoconst’riction in crucial parts of the vascular bed ?~y some unknown metabolic factor. Both these explanations suggest autoregulation of ON blood flow.
In the present study no significant reduction was observed on the stimulated sick. Although a very large dose of spheres was used very few were trapped within the optic nerve head (ONH) and the variability of the blood flow values was considerable. (The 95% confidence interval for the mean effect on ONH blood flow of sympathetic Aimulation was from a 52% increase to a 66% reduction.) Thus it seems clear that stimulation of the cervical sympathetic chain in monkeys influences blood flow differently in the various vascular beds of the eye. Significant blood flow reductions of various degrees were observed for the different parts of the uvea while no effects on blood flow through retina and ON w&s observed. The error for ONH blood flow determinations was too large to permit any conclusions regarding the effect of sympathetic tone on ONH blood flow. ACKNOWLEDGMENTS
This work was supported by PHS grant EY 00475 from the Kational Eye Institute and by a grant B74-14X-147 from the Swedish 3Iedical Research Council. The author thanks Professor Anders Bill for valuable discussions during the experiments and the preparation of the manuscript, and Miss Monica Thor&r and Nrs Anita Gstberg for skilful technical a.ssistance. REFERENCES
Aim, 3. (1975). The effect of stimulation of the cervical sympat’hetic chain on regional cerebral blood flow in monkeys. Acta Physiol. &and. 93, 483-9. A. and Bill, A. (1972). The oxygen supply to t,he retina, II. Effects of high intraocular pressure and of increased arterial carbon dioxide tension on weal and retinal blood flow in cats. Acta Physiol. Xcand. 84, 306-19. Aim, B. and Bill, A. (1973a). The effect of stimulation of the cervical sympathetic chain on retinal oxygen tension and on uveal, retinal and cerebral blood flow in cats. Acta Physiol. &and. 88,84-94. Xlm,
24
9. ALM
Alm, 8. and Bill, A. (197313). Ocular and optic nerve blood flow at normal and increased intraocular pressures in monkeys (Macaca irus) : a study with radioactively labelled microspheres including flow determinations in brain and some other tissues. Eqn. Eye Rex. 15, 15-29. Buckberg, G. D., Luck, J. C., Payne, D. B., Hoffman, J. I. E., Archie, J. P. and Fixler, D. E. (1971). Some sources of error in measuring regional blood flow with radioaetive microspheres. J. Appl. Physiol. 31, 598-604. Ehinger, B. (1966). Adrenergic nerves t.o t,he eye and to related structures in man and in the cynomolgus monkey (Macaca irus). Exp. Eye Res. 5, 42-52. Hayreh, S. S. (1970). Pathogenesis of visual field defects. Rr. J. Ophthalmol. 54, 289-311. Laties, A. RI. and Jacobowitz, D. ,4. (1966). B comparative study of the autonomic innervation of the eye in monkey, cat and rabbit. Anat. Rec. 156,383-96. Porsaa, K. (1941). Experimental studies on the vasomotor innervation of the retinal arteries. Acta Ophthalmol. (Kbh). Suppl. 18. Weiter, J. J., Schachar, R. A. and Ernest, J. T. (1973). Control of intraocular b!ood flow. II Effects of sympathetic tone. Invest. Ophthalmol. 12, 3324.