Download Effect of Sympathetic Stimulation on Critical Closure of

Effect of sympathetic stimulation on
critical closure of intraocular
blood vessels
Milton Best, Michael Blumenthal, Samuel Masket, and Miles A. Galin
Acute common carotid occlusion in rabbits causes a reduction in ocular blood volume and
ciliary artery blood pressure. At all levels of intraocular pressure, cervical sympathetic stimulation reduces these changes. The ocidar blood volume reduction after acute common carotid
occlusion is not linearly related to the absolute blood pressure change or to the lowest blood
pressure reached in the ciliary artery; it is related to the effective perfusion pressure after
occlusion. Effective perfusion pressure is equal to ciliary artery blood pressure minus intraocular pressure and it reflects the transmural pressure of ocular blood vessels.. The effective
perfusion pressure at which the peak ocular volume change occurs after acute common carotid
occlusion reflects the critical closing pressure of the ocular blood vessels. This approaches zero
in the absence of sympathetic stimulation and is 10 mm. Hg or greater in the presence of
sympathetic stimulation.
Key words: critical closure, sympathetic stimulation, carotid occlusion, effective perfusion
pressure, ciliary artery blood pressure.
demonstrated by both perfusion and tonographic techniques.1 Acute common carotid occlusion causes the greatest reduction
in ocular blood volume when the intraocular pressure is between 40 and 50 mm.
Hg. Above this level the effect of acute
common carotid occlusion on ocular blood
volume decreases rapidly.
Ocular blood volume is determined in
part by the difference between intraluminal blood pressure in the ocular blood vessels and the intraocular pressure that surrounds them. This difference is termed
transmural pressure, and it is affected by
changes in hydrostatic pressure on either
side of the blood vessel wall. Since blood
vessel radius is directly related to transmural pressure within certain limits, ocular
_Lhe semilogarithmic relationship between ocular blood volume change and
intraocular pressure after acute common
carotid occlusion in animals has been
From the Departments of Ophthalmology, New
York Medical College, Bird S. Coler Hospital
Division, Center for Chronic Disease, Welfare
Island, New York, N. Y., and the Hadassah
Medical School, Jerusalem, Israel.
Aided by United States Public Health Service
Grant No. NB 07162-03, American Heart Association Grant No. 69-869, and American Cancer
Society Grant No. T-517.
Manuscript submitted April 7, 1970; manuscript
accepted Aug. 6, 1970.
Reprint requests: Dr. Milton Best, Bird S. Coler
Hospital, Welfare Island, New York, N. Y.
10017.
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Best et at.
blood volume is also directly related to
transmural pressure. The reduction in intraocular blood volume caused by acute
common carotid occlusion may be explained by the acute fall in transmural
pressure that occurs within the ocular vascular bed. As intraocular pressure is increased from 20 to 50 mm. Hg, a larger
reduction in intraocular blood volume occurs after acute common carotid occlusion,
due possibly to the greater compression of
the vascular bed by the higher intraocular
pressure. At very high levels of intraocular
pressure, however, when filling of the vascular tree is resisted by the intraocular
pressure, the effect of acute common carotid occlusion will not be as great.
It is possible that acute common carotid
occlusion at intraocular pressures of 40 to
50 mm. Hg reduces transmural pressure
sufficiently that the critical closing pressure of intraocular vessels is exceeded. By
critical closing pressure is meant the transmural pressure at which ocular blood vessels collapse and flow through them
ceases.2 If critical closure of the ocular
vessels occurs at this level of intraocular
pressure, then the maximum effect of acute
common carotid occlusion on ocular blood
volume would become manifest. At intraocular pressures above this level the vascular bed will have already been reduced
by the high intraocular pressure so that
acute common carotid occlusion would not
cause as large a reduction in ocular blood
volume even if critical closure did occur.
If this analysis is correct, it would appear
that the intraocular pressure at which
acute common carotid occlusion causes the
maximum ocular blood volume change
represents the point at which critical closure of intraocular vessels occurs. The
present study was designed to consider
this possibility.
Materials and methods
Rabbits weighing between 2 and 3 kilograms
were anesthetized with 25 mg. of intravenous
pentobarbital sodium (veterinary Somnopentyl);
small additional amounts were injected as needed.
Proparacaine was used topically. The perfusion
technique used in this laboratory to measure ocular
blood volume change after acute common carotid
occlusion at controlled levels of intraocular pressure has been described previously1 and is schematically illustrated in Fig. 1. A 5 cm. length
of the common carotid artery was exposed and
freed of its sheath. The cervical sympathetic nerve
was isolated 1 cm. below the thyroid cartilage and
a stimulating electrode was attached to it at this
point. A rectangular pulse 0.6 to 2.4 v. in intensity
and 0.1 msec, in duration was delivered at a rate
of 4 per second by an isolated dual stimulator.
Intraocular pressure was controlled by an open
manometric system that communicated with the
anterior chamber through a 23 gauge needle so
that during acute common carotid occlusion intraocular pressure was kept constant.
After disinserting the lateral rectus muscle, the
temporal long posterior ciliary artery was isolated
and its blood pressure was measured just posterior
to its entrance into the sclera, using a PE 10
polyethylene cannula attached to a pressure transducer and a dynograph. Acute common carotid
occlusion was accomplished with rubber-tipped
forceps. Simultaneous measurements were made of
changes in ocular volume and ciliary artery blood
pressure after acute common carotid occlusion
with and without sympathetic stimulation.
Results
Fig. 1. Schematic diagram of perfusion apparatus
to measure ocular blood volume change after acute
common carotid occlusion.
Sympathetic stimulation reduces the intraocular blood volume change that occurs
after acute common carotid occlusion at all
intraocular pressures studied. Fig. 2 reflects
the typical relationship between ocular
blood volume change after acute common
carotid occlusion and intraocular pressure
with and without sympathetic stimulation.
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Sympathetic stimulation and intraocular bloodvessels 913
It should be noted that the peak intraocular blood volume change during sympathetic stimulation occurs at lower intraocular pressure levels than when sympathetic stimulation is omitted. Though the
slopes of the recorded curves differed in
40
35
30
25
Ab
i l l 20
15
20
30
40
50 60 70 80
INTRAOCULAR PRESSURE- mm Hg
Fig. 2. Ocular blood volume changes (&b) after
acute common carotid occlusion. Note that these
changes are greater and peak at a higher intraocular pressure without (solid line) than with
(interrupted line) sympathetic stimulation. Characteristics of stimulation are 1.9 v., 0.1 msec, four
per second.
several animals, the over-all findings were
similar. Fig. 3 demonstrates the finding of
a sharp increase in the slope of the curve
at intraocular pressures above 40 mm. Hg,
both with and without sympathetic stimulation. In most animals studied, a semilogarithmic relationship was demonstrated
between intraocular pressure and ocular
volume change after acute common carotid
occlusion for a range of intraocular pressures from 20 to 50 mm. Hg.
The ciliary artery blood pressure change
after acute common carotid occlusion was
similar at all levels of intraocular pressure
studied. In addition, the ocular blood
volume change after acute common carotid occlusion at differing levels of intraocular pressure was not linearly related to
the absolute change in ciliary blood pressure or the lowest blood pressure obtained
in the ciliary artery. A good correlation
with the blood volume changes at each intraocular pressure is noted, however, when
the effective perfusion pressure (ciliary artery blood pressure minus intraocular pressure) after acute common carotid occlusion is plotted against intraocular pressure
(Fig. 4). Blood volume change increases
as the effective perfusion pressure decreases and the peak blood volume change
occurs when the effective perfusion pressure approaches zero. Once the effective
5
15
10
l0
20
15
Ab
JUl
25
30
5
20
30
40 45 50 55 60
35
70 80
INTRAOCULAR PRESSURE- mm Hg
Fig. 3. Ocular blood volume changes after acute
common carotid occlusion. At intraocular pressures greater than 40 mm. Hg a sharp increase in
the slope of the curves occurs both with (interrupted line) and without (solid line) sympathetic
stimulation. Characteristics of stimulation are 1.9
v., 0.1 msec, four per second.
10
20
30 40 50
70 90
INTRAOCULAR PRESSURE-mm Hg
Fig. 4. Ocular blood volume change after acute
common carotid occlusion. Note that this volume
change (solid line) is related to effective perfusion pressure (interrupted line) at each level of
intraocular pressure.
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Best et al.
SYMPATHETIC STIMULATION
Fig. 5. Effect of acute common carotid occlusion on ciliary artery blood pressure in the presence
and absence of sympathetic stimulation (1.2 v., 0.1 msec, four per second.). A and C, carotid
occlusion; B to D, sympathetic stimulation; intraocular pressure, 40 mm. Hg.
-1 MIN-
100-
SYMPATHETIC STIMULATION
Fig. 6. Effect of acute common carotid occlusion on ciliary artery blood pressure at different
time intervals during sympathetic stimulation (1.2 v., 0.1 msec, four per second). A, B, and
C, carotid occlusion; intraocular pressure, 50 mm. Hg.
perfusion pressure after acute common carotid occlusion becomes less than zero, the
blood volume change begins to decrease.
Cervical sympathetic stimulation decreases the magnitude of changes that occur in ocular blood volume and in ciliary
artery blood pressure after acute common
carotid occlusion. Fig. 5 shows the change
in ciliary artery blood pressure that occurs
during acute common carotid occlusion. In
the absence of sympathetic stimulation such
occlusion (A) causes a rapid and sizeable
fall in blood pressure with rapid recovery
to the base line on release of the carotid
artery. Maintained sympathetic stimulation
alone (B) causes a fall in blood pressure
which subsequently returns to or exceeds
the original base line. Carotid occlusion
during sympathetic stimulation (C) causes
a much smaller fall in blood pressure than
originally observed without sympathetic
stimulation. When sympathetic stimulation
is stopped the blood pressure gradually returns to the base line.
Sympathetic stimulation limits the fall
in ciliary artery blood pressure induced by
acute common carotid occlusion as shown
in Fig. 6. The acute fall in ciliary artery
blood pressure reaches the same level
whether carotid occlusion is performed in
the first few seconds after sympathetic
stimulation when ciliary blood pressure is
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Sympathetic stimulation and intraocular bloodvessels 915
decreasing (B) or after 10 to 15 seconds
when ciliary blood pressure has recovered
(C).
During sympathetic stimulation the ocular blood volume change after acute common carotid occlusion at varying intraocular pressures was not linearly related
to the ciliary artery blood pressure fall or
the lowest ciliary artery blood pressure
reached. A plot of effective perfusion pressure during acute common carotid occlusion shows a good correlation with ocular
blood volume change (Fig. 7). Blood
volume change increases as effective perfusion pressure decreases, and the peak
blood volume change occurs when the effective perfusion pressure is 10 mm. Hg
or greater.
Table I lists the effective perfusion pressures at which the peak ocular blood
volume changes occurred in eight animals
with and seven animals without sympathetic stimulation. The difference in means
is significant at a level of P < 0.01.
Discussion
CO
10 £2
Ab
ill
20
-
30
|
40 1
50
^
60 §
10
15 20
30 40 50 70 90
^
INTRAOCULAR PRESSURE-mm Hg
Fig. 7. Ocular blood volume change after acute
common carotid occlusion during sympathetic
stimulation. Note that the volume change (solid
line) is related to the effective perfusion pressure
(interrupted line) at each intraocular pressure.
Characteristics of stimulation are 1.9 v., 0.1
msec, four per second.
Table I. Effective perfusion pressures (mm.
Hg) at which peak ocular blood volume
changes occurred
Without sympathetic
stimulation
0
0
5
3
-8
i—i
This study confirms that for intraocular
pressures in the range of 20 to 50 mm. Hg,
a semilogarithmic relationship exists between the intraocular pressure and the decrease in ocular blood volume caused by
acute common carotid occlusion. The maximum ocular blood volume change usually
occurs at intraocular pressures of approximately 50 mm. Hg, but occasionally occurs
at intraocular pressures as high as 70 mm.
Hg. Though a similar semilogarithmic relationship exists during cervical sympathetic
stimulation and acute common carotid occlusion, the blood volume changes in the
eye are much smaller.
The decrease in ciliary artery blood
pressure after acute common carotid occlusion was similar at all intraocular pressures between 20 and 80 mm. Hg, regardless of the state of sympathetic tone. Blood
pressure changes in the ciliary vessels,
therefore, cannot explain the relationship
between ocular blood volume change and
intraocular pressure found in these and
o §
-4
Mean±S.E. -0.4 ±1.5
With sympathetic
stimulation
12
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15
12
10
10
18
24
14.0+1.7
other studies.1'3 A more likely explanation
lies in a consideration of the changes in the
transmural pressure of the intraocular vessels at various levels of intraocular pressure.
The best estimate of transmural pressure
from the data of this study is the perfusion
pressure in the ciliary artery minus the intraocular pressure. We have termed this
the effective perfusion pressure, and during
acute common carotid occlusion it is equal
to the lowest blood pressure in the ciliary
artery minus the intraocular pressure. The
data indicate that as the effective perfusion pressure and, therefore, the transmural
pressure decrease, the ocular blood volume
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Investigative Ophthalmology
November 1970
Best et al.
change induced by acute common carotid
occlusion increases (Figs. 4 and 7). In the
absence of sympathetic stimulation the
maximum ocular blood volume change
after acute common carotid occlusion occurs when the effective perfusion pressure
approaches zero. This reflects a transmural
pressure close to zero, a state in which
critical closure of ocular blood vessels is
likely to occur.2 It is quite possible, therefore, that the effective perfusion pressure
at which the peak ocular blood volume
change occurs is a measure of the critical
closing pressure of the intraocular blood
vessels.
When acute common carotid occlusion
is performed during cervical sympathetic
stimulation the peak ocular blood volume
change occurs at an effective perfusion
pressure of 10 mm. Hg or greater, indicating that critical closure occurs at higher
transmural pressures when sympathetic
tone is increased in the eye. This has been
demonstrated for vascular beds in other
parts of the body.4
The smaller blood volume changes induced in the eye by acute common carotid
occlusion during sympathetic stimulation,
as compared to those without stimulation,
are due to the smaller falls in ciliary artery
blood pressure, and, therefore, larger transmural pressures. In the present study the
most frequent effect of cervical sympathetic
stimulation on the homolateral ciliary artery
blood pressure was a fall of approximately
7 mm. Hg for eight to ten seconds followed
by a recovery during the next 30 seconds
to levels approximately 8 mm. Hg above
the prestimulation base line (Fig. 5). The
blood pressure fall induced in the ciliary
artery by acute common carotid occlusion
during sympathetic stimulation was noted
to depend on the level of blood pressure
at the time of occlusion, but its lowest level
was constant and was about 18 to 20 mm.
Hg higher than without sympathetic stimu-
lation (Fig. 6). This corresponds to the
finding that, in the presence of an occluded common carotid artery, subsequent
stimulation of the ipsilateral cervical sympathetic chain for five minutes raises the
ciliary artery blood pressure about 30 mm.
Hg.5
This study emphasizes that, in the consideration of ocular blood volume changes
following acute common carotid occlusion,
the most important variable is the effective
perfusion pressure of the ocular blood vessels after occlusion. This reflects the transmural pressure of the ocular blood vessels
and is important in attempts at quantifying
analysis of the carotid compression tonography test.G> " In addition, the techniques
described in this investigation may offer
a means of analyzing the therapeutic effects of vasodilators and ganglionic blocking agents on ocular blood volume and
vasomotor tone.
REFERENCES
1. Best, M., Pola, R., and Galin, M. A.: Ocular
volume and common carotid occlusion in the
rabbit, INVEST. OPHTHAL. 8: 365,
1969.
2. Best, M., Blumenthal, M., Futterman, H. A.,
and Galin, M. A.: Critical closure of intraocular blood vessels, Arch. Ophthal. 82: 385,
1969.
3. Best, M., Pola, R., and Galin, M. A.: Ocular
volume and pressure change during common
carotid compression in the human, read before
the Atlantic Sectional Meeting of the Association for Research in Vision and Ophthalmology,
March 7, 1969.
4. Girling, F.: Vasomotor effects of electrical
stimulation, Amer. J. Physiol. 170: 131, 1952.
5. Bill, A.: Effects of cervical sympathetic tone
on blood pressure and uveal blood flow after
carotid occlusion, Exp. Eye Res. 2: 203, 1963.
6. Best, M., Pola, R., and Galin, M. A.: Intraocular pressure and common carotid occlusion.
I. Mathematical considerations, Exp. Eye Res.
Submitted.
7. Best, M., Pola, R., and Galin, M. A.: Intraocular pressure and common carotid occlusion.
II. Human studies, Exp. Eye Res. Submitted.
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