The effect of exercise on intraocular
pressure
II. Rabbits
Daniel F. Marcus,* Theodore Krupin, Steven M. Podos, and Bernard Becker
Intraocular pressure was found to decrease after treadmill exercise in rabbits. This fall was
associated with an increase in plasma osmolarity and blood lactate and a decrease in blood
pH. The alteration in intraocular pressure was reproduced by consecutive injections of hyperosmotic sodium lactate and isosmotic hydrochloric acid in amounts to duplicate the rise in
plasma osmolarity and the fall in blood pH induced by exercise.
Key words: exercise, rabbits, intraocular pressure, acidosis, blood lactate, plasma osmolarity.
I
exercise on intraocular pressure utilizing a
rabbit model.
ntraocular pressure was noted to decrease after physical exercise in human
beings.1"3 This fall was not associated with
changes in outflow facility or episcleral
venous pressure.2 It was related to a rise
of blood lactate and plasma osmolarity and
a fall in blood pH.3 The purpose of this
study was to elucidate further the effects of
Methods and materials
Male albino rabbits, weighing 2 to 3 kilograms, were used (Eldridge Rabbitry, St. Louis,
Mo.). Unconditioned animals were exercised on
a specially constructed, constant speed, motordriven treadmill (Figs. 1 and 2). Animals were
not used for more than one experiment. Heparinized blood samples were obtained from the central artery of the ear for pH, osmolarity, and
lactate determinations. Intravenous solutions were
injected in the marginal ear vein with subsequent
arterial samples obtained from the opposite ear.
Plasma osmolarity was measured by freezing
point depression with an Advanced Osmometer;
pH was measured on whole blood using an expanded scale Beckman pH meter at 37° C ; lactate
was determined on whole blood by the lactic dehydrogenase enzymatic method (Sigma Chemical
Company, St. Louis, Mo.); and intraocular pressure was measured with a Mackay-Marg electronic
tonometer (Berkeley Tonometer Company, Berkeley, Calif.) using only topical 0.5 per cent proparacaine hydrochloride anesthesia.
Baseline intraocular pressures and arterial blood
samples were obtained from six rabbits. Each
From the Department of Ophthalmology and the
Oscar Johnson Institute, Washington University
School of Medicine, St. Louis, Mo.
This study was supported in part by National
Eye Institute Grant EY 00004 from the National Institutes of Health, Bethesda, Md.
Manuscript submitted July 17, 1970; manuscript
accepted Aug. 7, 1970.
Reprint requests: Dr. Bernard Becker, Department
of Ophthalmology, Washington University
School of Medicine, 660 S. Euclid Ave., St.
Louis, Mo. 63110.
0
Present address: Department of Ophthalmology,
Marquette School of Medicine, Milwaukee,
Wis.
753
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754 Marcus et al.
rabbit was then exercised for four minutes on the
treadmill with repeated intraocular pressures and
blood samples being obtained immediately (within one minute), and at 15, 30, and 60 minutes
after exercise.
Six rabbits were given 0.5 ml. of 1/1,000 epinephrine hydrochloride subcutaneously. Baseline
intraocular pressures were measured 15 minutes
later and the animals were then exercised for four
minutes, Intraocular pressure was measured immediately and 15 minutes later.
Hyperosmotic sodium lactate (1,300 mOsm.
per liter, pH 7.2) was administered intravenously
to two groups of six rabbits in total doses of
7.5 and 10 ml. Blood samples for pH, lactate,
Investigative Ophthalmology
October 1970
and osmolarity were taken and intraocular pressure was measured before and immediately (within one minute) following administration. Isosmotic
sodium lactate, 40 nil., (291 mOsm. per liter,
pH 7.2) was given intravenously to six rabbits.
Intraocular pressure, blood pH, plasma osmolarity,
and blood lactate were measured before, immediately after (within one minute), and 15
minutes after injection.
Isosmotic hydrochloric acid (291 mOsm. per
liter, pH 1) was infused intravenously in a dose
of 7 ml. in six rabbits. Intraocular pressure, blood
pH, and plasma osmolarity were measured before, immediately after (within one minute), and
15 minutes after infusion.
Consecutive intravenous administration of both
10 ml. of hyperosmotic sodium lactate and 7
ml. of isosmotic hydrochloric acid was performed
in six rabbits. Intraocular pressure and an arterial
blood sample for pH and plasma osmolarity were
obtained before and immediately (within two
minutes) after injections.
Statistics were analyzed using the paired-t test
for individual changes and Student's-t test for
group changes.
Results
Fig. 1. Side view of rabbit treadmill.
Exercise. The mean values of intraocular
pressure, blood pH, plasma osmolarity",
and blood lactate after exercise are shown
in Table I. The maximal decrease of intraocular pressure and blood pH and the
Fig. 2. Top view of rabbit treadmill with rabbit in place.
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Volume 9
Number 10
Exercise on intraocular pressure: Rabbits 755
maximal increase of plasma osmolarity and
blood lactate occurred immediately after
exercise (p < 0.001). There was a significant (p < 0.005) fall in intraocular
pressure at 15 and 30 minutes, with recovery by one hour. Blood lactate and
plasma osmolarity returned to pre-exercise
levels at one hour, while blood pH returned to baseline levels by 30 minutes.
Exercise
mmHg
•25
mOsm/L
+ 15
0
PH
-.10
ImMoles/L
0
15
30
60
TIME (MINUTES) AFTER EXERCISE
Fig. 3. Average changes for selected parameters
(mean ± S.E.M.) induced by exercise in six normal
rabbits.
These changes are summarized in Fig. 3.
Epinephrine. Pretreatment with systemic
epinephrine hydrochloride did not alter the
hypotensive effect of exercise. There was
an average fall of 8.5 ± 0.6 (mean ±
S.E.M.) mm. Hg immediately following
exercise.
Sodium lactate. Table II lists the effects
of 7.5 and 10.0 ml. intravenous infusions
of hyperosmotic sodium lactate. Both dosage levels produced immediate significant
increases of blood lactate and plasma osmolarity and significant decreases of intraocular pressure. A greater magnitude of
change was seen after the 10 ml. dose.
These changes were not associated with alterations of blood pH. An infusion of isosmotic sodium lactate, containing the same
number of grams as 7.5 ml. of the hyperosmotic solution, did not alter intraocular
pressure, plasma osmolarity, or blood pH,
but produced elevation of blood lactate
(Table III).
Hydrochloric acid. Intravenous isosmotic
hydrochloric acid produced an immediate
and significant fall in blood pH and intraocular pressure while plasma osmolarity
was not altered (Table IV).
Sodium lactate and hydrochloric acid.
Intravenous administration of both hyperosmotic sodium lactate and isosmotic
hydrochloric acid immediately resulted in
a significantly decreased intraocular pressure and blood pH and an increased
plasma osmolarity (Table V).
Table I. Effect of exercise on intraocular pressure, blood pH, plasma osmolarity,
and blood lactate of six normal rabbits (mean ± S.E.M.)
Characteristic
Intraocular pressure
(mm. Hg)
Blood pH
Plasma osmolarity
(mOsm. per liter)
Blood lactate
(mmoles per liter)
Baseline
19.5
±0.4
7.40
±0.02
306
±6
4.3
±0.8
Immediately
12.7
±0.7
7.25
±0.02
331
±7
10.8
±1.0
Measurement after exercise (min.)
15
30
|
17.3
17.8
±0.7
±0.6
7.34
±0.01
317
±6
9.1
±0.8
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7.40
±0.02
315
±7
6.9
±0.8
60
18.8
±0.4
7.43
±0.02
309
±4
4.0
±0.6
Investigative Ophthalmology
October 1970
756 Marcus et al.
Table II. Effect of intravenous hyperosmotic sodium lactate on intraocular
pressure, plasma osmolarity, blood lactate,
and blood pH of six normal rabbits
(mean± S.E.M.)
Table III. Effect of intravenous isosmotic
sodium lactate* on intraocular pressure,
blood pH, plasma osmolarity, and blood
lactate of six normal rabbits (mean ± .
S.E.M.)
Measurement after
infusion (min.)
ImmeBaseline diately
15
Dose
(ml.)
7.5
Characteristic
Baseline
Measurement immediately after infusion
Intraocular pressure (mm. Hg)
15.5
±0.4
12.0*
±0.2
Blood pH
7.41
±0.02
7.46
±0.03
Plasma osmolarity (mOsm.
per liter)
10
296
±2
310f
±3
Blood lactate
(mmoles per
liter)
9.1
±1.6
16.4*
±1.2
Intraocular
pressure
(mm. Hg)
18.0
±0.7
13.6*
±0.7
Blood pH
7.47
±0.02
7.45
±0.02
Plasma osmolarity (mOsm.
per liter)
Blood lactate
(mmoles per
liter)
293
±3
5.9
±0.9
320*
±3
Characteristic
Intraocular pressure
(mm. Hg)
14.3
±0.2
13.9
±0.4
14.8
±0.4
Blood pH
7.42
±0.03
7.43
±0.03
7.48
±0.02
Plasma osmolarity
299
(mOsm. per liter) ±2
Blood lactate
(mmoles per
liter)
8.7f
±1.2
Table IV. Effect of intravenous isosmotic
hydrochloric acid* on intraocular pressure,
blood pH, and plasma osmolarity of
six normal rabbits (mean ± S.E.M.)
Characteristic
Intraocular pressure
(mm. Hg)
Blood pH
Discussion
The present investigation demonstrates
that intraocular pressure can be lowered in
rabbits after treadmill exercise. The fall
in intraocular pressure is of the same
magnitude as that seen in human beings,3
but is of shorter duration. Associated with
the decrease in intraocular pressure are
elevations of blood lactate and plasma osmolarity and lowering of blood pH (Table
I)Exercise is known to increase circulating epinephrine levels4 which could possibly influence intraocular pressure. Injecting rabbits with epinephrine before
exercise did not alter the effects of the
exercise on intraocular pressure. There-
11.5f
±1.6
296
±2
•40 ml. isosmotic sodium lactate (291 mOsm. per liter,
pH 7.2) per animal.
t Significant difference between baseline value and value
at designated time after infusion, p < 0.005.
21.0*
±1.3
"Significant difference between baseline and immediate
value, p < 0.001.
f Significant difference between baseline and immediate
value, p < 0.01.
5.6
±0.9
296
±2
Plasma osmolarity
(mOsm. per
liter)
Measurement after
infusion (min.)
ImmeBaseline diateh/
15
16.1
±0.7
11.8 f
±0.8
16.7
±0.6
7.45
±0.03
7.29f
±0.02
7.40
±0.03
296
±1
298
+2
295
±2
•7 ml. of isosmotic hydrochloric acid (291 mOsm. per
liter, pH 1.0) per rabbit.
f Significant difference between baseline value and value
at designated time after infusion, p < 0.005.
fore, it seems unlikely that epinephrine
plays a role in reducing intraocular pressure after exercise.
Intravenous administration of the same
gram amount of isosmotic sodium lactate
as given in the 7.5 ml. hyperosmotic injection does not alter intraocular pressure,
plasma osmolarity, or blood pH, despite
higher blood lactate levels than those seen
after exercise (Table III). Therefore, the
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Niunber 10
Exercise on intraocular pressure: Rabbits 757
Table V. Effect of consecutive intravenous administration of both 10 ml.
hyperosmotic sodium lactate and 7 ml.
isosmotic hydrochloric acid on intraocular
pressure, blood pH, and plasma osmolarity of six normal rabbits (mean ±
S.E.M.)
Baieline
Measurement immediately after
infusions
Intraocular pressure
(mm. Hg)
17.5
±0.7
10.9 °
±0.6
Blood pH
7.45
±0.07
7.30*
±0.02
Characteristic
Plasma osmolarity
(mOsm. per liter)
300
±2
323
±3
*
"Significant difference between baseline and immediate
values, p < 0.005.
lactate-induced decrease in intraocular
pressure after exercise appears to be due
to the rise in plasma osmolarity rather
than the elevation of lactate itself.
Hyperosmotic intravenous sodium lactate
lowers intraocular pressure but does not
alter blood pH (Table II). The increase in
blood lactate after the 7.5 ml. dose is
similar to that seen after exercise, while the
fall in intraocular pressure and the rise in
plasma osmolarity are of lesser magnitude.
Thus, not all of the increase in plasma
osmolarity can be accounted for by increases in blood lactate. After acute exercise, other factors play a role in increasing
plasma osmolarity: sweating with resultant
water loss; increased blood pressure in
capillaries which is associated with the
rise in systolic blood pressure and movement of fluid from the blood into tissue
spaces; and an increase in intracellular
osmolarity due to increased metabolism
which leads to osmotic absorption of fluid
into the cells.5 The 10 ml. dose of hyperosmotic sodium lactate produces a rise in
plasma osmolarity similar to exercise, but
a greater elevation of blood lactate (p
< 0.001) and a lesser fall of intraocular
pressure. Thus, not all of the intraocular
pressure effects can be accounted for by
osmolarity changes.
Intravenous isosmotic hydrochloric acid
does not alter plasma osmolarity, but lowers blood pH and intraocular pressure.
With blood pH changes similar to that
induced by exercise, the fall in intraocular
pressure is of lesser magnitude (p <
0.005).
Administration of both hyperosmotic
sodium lactate and isosmotic hydrochloric
acid, in amounts to duplicate the rise in
plasma osmolarity and fall in blood pH
induced by exercise, immediately lowers
intraocular pressure to similar levels as
those seen after exercise.
It seems reasonable to conclude that
two factors contribute to the decrease in
intraocular pressure in rabbits after exercise: a decrease in blood pH and an increase in plasma osmolarity.
REFERENCES
1. Lempert, P., and Cooper, K.: The effect
of exercise on intraocular pressure, Amer. J.
Ophthal. 63: 1673, 1967.
2. Stewart, R. H., LeBlanc, R., and Becker,
B.: Effects of exercise on aqueous dynamics,
Amer. J. Ophthal. 69: 245, 1970.
3. Marcus, D. F., Krupin, T., Podos, S. M., and
Becker, B.: The effects of exercise on intraocular pressure. I. Human beings, INVEST.
OPHTHAL. 9: 749,
1970.
4. Gordon, R., Spector, S., Sjverdsma, A., and
Undenfriend, S.: Increased synthesis of epinephrine and norepinephrine in the intact rat
during exercise and exposure to cold, J.
Pharm. Exp. Ther. 153: 440, 1966.
5. Morehouse, L. E., and Miller, A. T.: Physiology of exercise, St. Louis, 1963, The C. V.
Mosby Company, p. 131.
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