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Unilateral control of uterine blood flow in the ewe
CURRENT INVESTIGATION
Unilateral control of uterine blood flow in the ewe FRANK
C.
GREISS,
HOWARD
B.
Winston-Salem,
North
JR.,
MILLER,
M.D. M.D.*
Carolina
The effects of intracavitary injection of estrogens into one horn of the ovine uterus on bilateral uterine blood flow (UBF) through the major supplying artery were evaluated in conscious castrate ewes. Ipsilateral UBF increased significantly while contralateral LJBF was unchanged. The results indicate that unilateral UBF is controlled primarily by the vascular reactivity of the ipsilateral uterine horn.
Methods
I N A. R E c E N T study,3 it was reported that the vascular beds of the two horns of a pregnant ovine uterus may react differently from seach other, dependent upon the presence or absence of placental cotyledons in each horn. In these experiments, uterine blood flow (UBF) was measured by electromagnetic flow probes implanted around the middle uterine artery. The validity of these observations is critically dependent upon the premise that blood flow through the monitored artery is controlled primarily, if not exclus:ively, by the vascular reactivity of the ipsilateral uterine horn. The purpose of the present report is to document this premise. From the Department of Obstetrics Gynecology, Bowman Gray School Medicine of Wake Forest University.
Under pentobarbital anesthesia, nonpregnant Western ewes were castrated, and polyvinyl catheters were implanted in each uterine horn. A No. 2 plastic suture was put around each horn at its juncture with the uterine body and placed immediately adjacent to the horn so that the blood vessels in the broad ligament were not encompassed. Each suture was tied snugly to isolate the cornual cavities. Evans blue dye was injected under moderate pressure into each uterine horn via the implanted catheter. In every ewe tested, the dye could not be recovered from the contralateral horn. The intrauterine catheters were passed through the abdominal wall and placed in a small plastic box attached to the skin. At the same procedure, electromagnetic flow probes and a zero occlusion loop were implanted around each uterine artery and the descending aorta,
and of
This investigation was suPPorted by United States Public Health Service Grant No. HE-0341-11 from the National Heart Institute.
respectively,
*Former Student Fellow in Reproductive Biology under United States Public Health Service Training Grant No. Tl -HD-69-05.
After surgical
299
as previously
described.ll
2
the ewes had recovered from the procedures, bilateral UBF’s were
300
Greiss
and
Miller
UBF’s wen* calculated e\.ery S minute> before estrogen injections arid alTeraged to establish control levels. UBF’s were calculated every 15 minutes during the first :! hours after estrogen injections and hourlv thereafter.
32 30 -\ 26 z 26 \ 24 2 x. 22 s 20 $ IS2 16s 5 4 $
Results
‘4 12 IO6-
I
11
0
I2 tiours
” 34 After
” 5 67 Introcov~lary
”
’
”
6 9 IO II Estrogen lnjechon
1
I2
Fig, 1. Effect of intracavitary injection of estrogen into one ovine uterine horn on bilateral UBF. Flow through the middle uterine artery ipsilateral to the injection changed significantly while that through the contralateral vessel remained essentially unchanged. monitored daily with the ewes stationed in a mobile cart in an isolated room. Test doses of 2 ml. of 0.9 per cent sterile sodium chloride solution (PSS) were injected into the cornual cavities, but no changes in UBF occurred. When UBF’s had stabilized at low postoophorectomy levels, the following experiment was performed. After a 30 to 45 minute control period, 20 pg of conjugated estrogens equine” dissolved in 0.25 ml. of PSS followed by SL& cient PSS to clear the catheter (1 to 1.5 ml.) was injected into the cavity of one uterine horn. Thereafter, bilateral UBF’s were monitored for the succeeding 12 hours. Multiple zero-flow determinations were made before, during, and after the experimental period. Two to 3 days later, when UBF’s had stabilized at pre-experimental rates, the same experiment was repeated except that estrogen was injected into the cavity of the opposite uterine horn.
Experiments were performed on 1 ewes beginning 3 to 8 days after the operative procedures. When estrogens were injected into the right uterine horn, blood flow through the right middle uterine artery increased markedly while flow through the left middle uterine artery was unchanged or varied unpredictably. When estrogens were injected into the left uterine horn of the same ewe, blood flow through the left middle uterine artery increased while that through the opposite artery was unchanged. Similar responses occurred in all ewes tested. Thus. each animal served as its own control. To pool the results. UBF’s through the arteq ipsilateral to estrogen injections, either right or left, were compared with those through the contralateral artery. Control UBF through the ipsilateral altery varied from 2.3 to 11.2 C.C. per minute. That through the contralateral artery varied from 3.3 to 16.7 C.C. per minute. Changes in UBF from control rates through the 2 arteries are summarized in Fig. 1. Contralateral UBF did not change significantly. Ipsilateral UBF increased two- to eightfold over control flow rates. With the exception of the 5 hour observation, ipsilateral changes were significantly different (P < 0.05) from contralateral ones one through 10 hours after estrogen injections. Comment The present study confirms the observation that estrogens induce marked vasodilatation in the nonpregnant uterus4 and demonstrates that this effect can be evoked by intracavitary injection of the hormone. It also supports the observation that estrogens are fixed by uterine tissues,” for if they were absorbed into the systemic circulation one would expect them to reach and cause vaso-
Volume 111 Number 2
Unilateral
dilation in the contralateral uterine horn. More pertinently, the present results demonstrate that vascular changes within a single ovine uterine horn are reflected almost exclusively by changes in UBF through the major ipsilateral supplying artery. While communicating blood vessels between the 2 horns -proximal to the regions occluded in the present experiment do exist, it appears
control
of uterine
blood
flow
301
doubtful that significant functional arterial cross-circulation occurs. It would seem, therefore, that differential cornual vascular reactivities can be determined with validity by the method described. The authors wish to thank the Ayerst Laboratories, Inc., New York, New York, for the hormone preparation used in this study.
REFERENCES
1.
Greirs,
F.
C.,
Jr.:
J. Appl.
F.
C.,
Jr.:
Obstet.
Physiol.
17:
177,
4.
21:
295,
5.
196i!. 2. Greiss,
Gynecol.
1963.
3. Greiss, F. C., Jr.: Ara. J. OBSTET. GYNECOL. In press.
G&s, F. C., Jr., and Anderson, S. G.: AM. 1. OBSTET. GYNECOL. 107: 829. 1970. jensen, E. V., Hurst, D. J., Dkombre, E. R., and Jungblut, P. W.: Science 158: 385, 1967.
Unilateral control of uterine blood flow in the ewe FRANK
C.
GREISS,
HOWARD
B.
Winston-Salem,
North
JR.,
MILLER,
M.D. M.D.*
Carolina
The effects of intracavitary injection of estrogens into one horn of the ovine uterus on bilateral uterine blood flow (UBF) through the major supplying artery were evaluated in conscious castrate ewes. Ipsilateral UBF increased significantly while contralateral LJBF was unchanged. The results indicate that unilateral UBF is controlled primarily by the vascular reactivity of the ipsilateral uterine horn.
Methods
I N A. R E c E N T study,3 it was reported that the vascular beds of the two horns of a pregnant ovine uterus may react differently from seach other, dependent upon the presence or absence of placental cotyledons in each horn. In these experiments, uterine blood flow (UBF) was measured by electromagnetic flow probes implanted around the middle uterine artery. The validity of these observations is critically dependent upon the premise that blood flow through the monitored artery is controlled primarily, if not exclus:ively, by the vascular reactivity of the ipsilateral uterine horn. The purpose of the present report is to document this premise. From the Department of Obstetrics Gynecology, Bowman Gray School Medicine of Wake Forest University.
Under pentobarbital anesthesia, nonpregnant Western ewes were castrated, and polyvinyl catheters were implanted in each uterine horn. A No. 2 plastic suture was put around each horn at its juncture with the uterine body and placed immediately adjacent to the horn so that the blood vessels in the broad ligament were not encompassed. Each suture was tied snugly to isolate the cornual cavities. Evans blue dye was injected under moderate pressure into each uterine horn via the implanted catheter. In every ewe tested, the dye could not be recovered from the contralateral horn. The intrauterine catheters were passed through the abdominal wall and placed in a small plastic box attached to the skin. At the same procedure, electromagnetic flow probes and a zero occlusion loop were implanted around each uterine artery and the descending aorta,
and of
This investigation was suPPorted by United States Public Health Service Grant No. HE-0341-11 from the National Heart Institute.
respectively,
*Former Student Fellow in Reproductive Biology under United States Public Health Service Training Grant No. Tl -HD-69-05.
After surgical
299
as previously
described.ll
2
the ewes had recovered from the procedures, bilateral UBF’s were
300
Greiss
and
Miller
UBF’s wen* calculated e\.ery S minute> before estrogen injections arid alTeraged to establish control levels. UBF’s were calculated every 15 minutes during the first :! hours after estrogen injections and hourlv thereafter.
32 30 -\ 26 z 26 \ 24 2 x. 22 s 20 $ IS2 16s 5 4 $
Results
‘4 12 IO6-
I
11
0
I2 tiours
” 34 After
” 5 67 Introcov~lary
”
’
”
6 9 IO II Estrogen lnjechon
1
I2
Fig, 1. Effect of intracavitary injection of estrogen into one ovine uterine horn on bilateral UBF. Flow through the middle uterine artery ipsilateral to the injection changed significantly while that through the contralateral vessel remained essentially unchanged. monitored daily with the ewes stationed in a mobile cart in an isolated room. Test doses of 2 ml. of 0.9 per cent sterile sodium chloride solution (PSS) were injected into the cornual cavities, but no changes in UBF occurred. When UBF’s had stabilized at low postoophorectomy levels, the following experiment was performed. After a 30 to 45 minute control period, 20 pg of conjugated estrogens equine” dissolved in 0.25 ml. of PSS followed by SL& cient PSS to clear the catheter (1 to 1.5 ml.) was injected into the cavity of one uterine horn. Thereafter, bilateral UBF’s were monitored for the succeeding 12 hours. Multiple zero-flow determinations were made before, during, and after the experimental period. Two to 3 days later, when UBF’s had stabilized at pre-experimental rates, the same experiment was repeated except that estrogen was injected into the cavity of the opposite uterine horn.
Experiments were performed on 1 ewes beginning 3 to 8 days after the operative procedures. When estrogens were injected into the right uterine horn, blood flow through the right middle uterine artery increased markedly while flow through the left middle uterine artery was unchanged or varied unpredictably. When estrogens were injected into the left uterine horn of the same ewe, blood flow through the left middle uterine artery increased while that through the opposite artery was unchanged. Similar responses occurred in all ewes tested. Thus. each animal served as its own control. To pool the results. UBF’s through the arteq ipsilateral to estrogen injections, either right or left, were compared with those through the contralateral artery. Control UBF through the ipsilateral altery varied from 2.3 to 11.2 C.C. per minute. That through the contralateral artery varied from 3.3 to 16.7 C.C. per minute. Changes in UBF from control rates through the 2 arteries are summarized in Fig. 1. Contralateral UBF did not change significantly. Ipsilateral UBF increased two- to eightfold over control flow rates. With the exception of the 5 hour observation, ipsilateral changes were significantly different (P < 0.05) from contralateral ones one through 10 hours after estrogen injections. Comment The present study confirms the observation that estrogens induce marked vasodilatation in the nonpregnant uterus4 and demonstrates that this effect can be evoked by intracavitary injection of the hormone. It also supports the observation that estrogens are fixed by uterine tissues,” for if they were absorbed into the systemic circulation one would expect them to reach and cause vaso-
Volume 111 Number 2
Unilateral
dilation in the contralateral uterine horn. More pertinently, the present results demonstrate that vascular changes within a single ovine uterine horn are reflected almost exclusively by changes in UBF through the major ipsilateral supplying artery. While communicating blood vessels between the 2 horns -proximal to the regions occluded in the present experiment do exist, it appears
control
of uterine
blood
flow
301
doubtful that significant functional arterial cross-circulation occurs. It would seem, therefore, that differential cornual vascular reactivities can be determined with validity by the method described. The authors wish to thank the Ayerst Laboratories, Inc., New York, New York, for the hormone preparation used in this study.
REFERENCES
1.
Greirs,
F.
C.,
Jr.:
J. Appl.
F.
C.,
Jr.:
Obstet.
Physiol.
17:
177,
4.
21:
295,
5.
196i!. 2. Greiss,
Gynecol.
1963.
3. Greiss, F. C., Jr.: Ara. J. OBSTET. GYNECOL. In press.
G&s, F. C., Jr., and Anderson, S. G.: AM. 1. OBSTET. GYNECOL. 107: 829. 1970. jensen, E. V., Hurst, D. J., Dkombre, E. R., and Jungblut, P. W.: Science 158: 385, 1967.