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The Effect of Pregnancy and the Corpus Luteum upon Vesical Muscle *
THE
EFFECT
ORTHELLO (From
R.
OF PREGNANCY AND THE CORPUS UPON VESICAL MUSCLE” LANGWORTHY,
the Subdepartment Johns
M.D.,
AND
C.
BERNARD
BALTIMORE, MD. of Neurology and, the Department Hopkins University and Hospital)
BRACK,
LUTEUM M.D.,
of Gynecology,
T
HE innervation of vesical muscle has been studied in this laboratory for several years. It became obvious in the course of the experiments that there were factors other than the nervous stimuli to be considered as influencing vesical activity. We early began to exclude pregnant cats from our series of experimental preparations. The bladder appeared to be capable of holding an unusually large volume of fluid at low pressures. This increased capacity was still present for days or weeks after pregnancy was terminated. The conclusion was reached that the vesical muscle was influenced in its capacity not alone by its nerve supply but also by chemical substances carried in the blood. It has been known for many years that changes in the urinary tract take place with pregnancy. These have been studied particularly in the ureters but have a direct relation to the present experiments. In 1843 Cruveilhier first described dilatation and elongation of the ureter as a frequent accompaniment of the gravid state. He believed that there was a hyperplasia of the tissues composing the walls of the kidney pelvis, the ureter, and the bladder in the form of increased thickness of the muscular and connective tissue elements. In spite of this hypertrophy the lumen of the ureter is dilated. The extent to which these ch,angesappeared varied much in different individuals as well as in the meters of the same individual, the process usually being more marked on the right side. Two explanations for these phenomena have arisen. One group has felt that the pressure of the enlarged uterus upon the ureter at the point where it crosses the pelvic brim was the chief factor. However, larger pelvic tumors than those represented by the pregnant uterus were not often productive of the ureteral changes in the nonpregnant pa.tient. Other authors have suggested an atony of the ureteral musculature. Dilatation of the ureter usually reaches its maximum at about the seventh month of pregnancy, and frequently diminishes toward term despite the enlargement and increasing weight of the uterus. Traut
and McLane (1936) studied contraction waves in the ureters of their The normal ureter of the nonpregnant woman is possessed of rhythmic peristaltic activity which can be measured and recorded. In the majority of patients this rhythmic activity is definitely changed in pregnancy in varying degrees. The altered peristaltic activity is expressed by diminished amplitude of the peristaltic wave commencing in the third month of pregnancy but reaching its peak during the -*Aided by a grant from the Committee on Scientific Research of the American Medical Association.
paitients.
121
122
AMERICAN
JOURNAL
OF
ORSTETRICS
AS0
GYNECOLOGY
seventh and eight months. -1fter the fifth month the number of patients showing diminished ureteral response exceeds those showing normal activity. During thr last month of pregnancy there seems to be a definite ret.unr of muscular irritability as expressed by the measurement of peristalsis and response to stimulation. This diminished peristaltic activity of the ureters seen in pregnancy cannot be explained on the basis of dilatation. on the contrary, dilatation of the uwiers during pegnancy is probably in great part dependcut upon tile ntony of the ureters. Th(? etiology of this ureteral atony during pregneney is, rn the opinion of the authors, not due to any mechanical factor but rather has somet as yet unexplained, chemical basis. Later Traut, MeLane and Kuder ll!):iij pointed uot t,hat the cllaracteristics 01 the ureteral atony are similar in many respects to those affecting the uterino musculature. It -as suggested that the phenomena jn the two organs may have a similar etiology. The ureteral dilat.ation is roughly proportional to the degree of atoay, and both appear and disappear at similar times with regard to the course of pregnancy. Dilatation and atony appear in the third month and are progressivr to the seventh month of pregnancy. During the last two months there is a marked increase in motility, accompanied by n moderate decrease in the dimensions of thr tract. Following delivery atony is again marked until the third week3 subsequent 10 whicah motility returns rapidly to normal level?, which arc usually attained during tllr sixth and seventh weeks post parturn. Dilatation of the tract tlrcreases progresGvelp after delivery and reaches practically the normal vxlucs :Lt the seventh ~4 of the puerperium. Hundley, Walton, Hibbitts, Siegel and Era& (l%!,>) felt that t,he atony of the, ureter must be the result of the activity of hormones elaborated during pregnancy. They found hypertrophy of the muscle, edema, and increased vaseularity in the whole urinarp tract. Other experiments more closely related lo the bladller have beeu performed IJ! i\‘trolsey and Brooks (1937). They placed cats for loug periods in metabolism cages cqnipped with apparatus for recording c~ontinuallp volume and t.ime of mieturition. Micturition volume diminished markedly (luring estrus or while the animal, femaitl Tn the -ftmmk iiw decrease W:LS or male, was under the intlurn~~c of l~r~)~~o~B. Tremendous inrrcasPs in correlated with the vaginal smcnr nncl rstrous c.WlP. micturition rolurnc w\‘Pre observed post paYtuTl1.
chose
to uw
vcrq’
easil\-.
tion. Previously
rabbits
Injection the
This
since
cor~)o~a
Illtea call bc produced
animal norm&c>vulates only nt the of anIuitrin-R also produces ovulation eat 1~s hpcn emplo~etl nlmost esrlnsivel~
in these anituals time of copt11:1iu the rabhit. for our studies
of vesical function. Catheterization of the urethra III the rabbit is difficult because the urethral meatus is well up in the vagina. However it was found possible to introduce a fine glass catheter through the urethra into the bladder of the rabbit and make readings of vesical activity after the same manner which has been employed in cats. The animals were always anesthetized with pentobarbital injected intravenously. Before any further procedures were instituted three control readings at ten-day intervals were made to learn the average vesieal capacity of the animals. If these readings showed little variation, the experiment was continued. In this work we used as the criteria of the experiment any changes from the normal vesical capacity which occurred during pregnancy and following ovulation. Records were made of intravesieal pressure during filling of the bladder; the pressure remained low until the viseus was reaching the limits of its capacity. The normal vesical capacity of an animal under deep anesthesia is remarkably constant as the readings show. Under pentobarbital anesthesia the vesical muscle does not contract reflexly (Eolb and Langworthy, 1938), and urine escapes only by overflow
L&NGWORTHY-BRACK
:
EFFECT
OF
PREGNANCY
ON
VESICAL
MUSCLE
123
when. the intravesical pressure is slowly raised to a point which is rather constant for the individual. The vesieal volume was increased by adding 2 C.C. of fluid at a time until this overflow occurred. Between each introduction of fluid the intravesical pressure was allowed to fall to a resting level. We felt that a demonstration of increased vesical volume developing coincidently with pregnancy suggested an atony of the vesical musculature such as has been shown for the ureters by Tram?. The rabbits did not stand the repeated administration of an anesthetic well and many were lost during the course of the experiments. For the same reason pregnancy The edema of the vagina and vulva subsewas not often carried to its termination. quent to ovulation and during pregnancy was an obstacle to successful catheterization of the urethra. A few animals developed intractable diarrhea with loss of weight. During the period of diarrhea the vesical volume was increased. Careful records of the weight If a rabbit was losing weight, it was of the animals were kept from week to week. dropped temporarily from the experiment. In general the changes in weight had no correlation with the results. The weights are recorded in the control series shown in Table I. TABLE
I.
CASTRATED
.__ EXP.
FIRST READIKG VOI..
WT.
1
8
2 3 4 5 6 7 8 9 16
14 26 16 26 26 48 20 40 30
4.5 6.0 5.5 6.5 6.0 5.0 7.0 4.75 3.5 4.5
__-
lo-DAY INTERVAT, VOI,. WT. 24 5.0 24 6.75 35 WI 22 7.0 18 6.5 S 5.25 26 8.0 3s 6.O 14 4.25 20 5.25 ESPERIMEKTAL
=I I
-
RABBITS ZZ
lo-DAY IKTERV.%L VOL. WT. 12 5.5 24 6.75 44 6.0 10 65 22 6.5 5.5 10 26 6.25 20 6.25 20 5.25 32 G.0
lo-DAY IXTERVAL VOL. WT. ___18 5.25 14 6.5 20 6.25 14 5.25 26 6.75 6 5.0 18 5.75 32 5.75 26 5.5 no I 5.75
OBSERVATIONS
A.. Table I shows the results of a study of ten control animals. The ovaries were removed from the young adult rabbits and they were allowed to recover from the operations. Subsequently a series of four readings of vesical volume was made upon each rabbit at ten-day intervals. After the first three readings the animals were each given 6.2 C.C. of antuitrin-S intravenously. The weight of the rabbit at the time of each reading is given in the chart. According to Dr. Franklin Synder this is sufficient hormone to produce ovulation. It will be observed that the rabbits tended to gain in weight during the progress of the experiment. The readings of vesical volume show only slight variations; ten days after the injection of antuitrin-S no significant changes in vesical volume appeared. II. The changes in vesical volume associated with pregnancy are shown in Table All the rabbits used in the experiments were young virgin females. The II. records are not complete in all the cases due to difficulty in keeping the rabbits alive and in catheterizing the bladder during pregnancy. The three control vesical readings are relatively constant for the single individuals. After the third reading the animal was placed with a male. The next Where pregnancy ensued there was in every reading was made ten days later. case an increase in the vesical volume. The normal volume was in several instances doubled or tripled. Inasmuch as the period of gestation in the rabbit is thirty days it was sometimes poss:ible to make three readings during the period of pregnancy; the results are shown in the tables. As the uterus increased in size there was in certain cases a diminution in the vesical capacity, although the capacity was still much greater than in the nonpregnant animal. Perhaps this was due to mechanical factors pro-
124
AMERICAN TABLE
JOURNAL II.
OF
EFFECT
ORSTRTRICS
OF PREGNANCY.
AND COXTROL
-
ZZ
--
.-
READINGS
__--
2 ODAYR' IT.
(
QYNECOLOQY
ODAYE IlATER
1LATER
10 DAYS FOLLOWING DELIVERY
;E iODAYE IATER _.--
-I_ 56 40
34 46
40 5G 36 34 24 32 ::4 ‘> . .,(I 24 28
58 “4
1
34 50
I I I ! i /
duced by the pressure of the gravid uterus. In other cases the bladder capacity continued to increase through the period of pregnancy. Following the termination of pregnancy the vesical volume was greater than at any previous period. It appeared that the bladder was free from any pressure from the uterus and could expand t,o the limits of its capacity. The bladder remained of large volume for three or four weeks following the termination of pregnancy, and it was only at the end of this time that it returned to its normal volume. C. The final series of experiments had to do with the production of ovulation in the normal rabbit by the injection of antuitrin-S. This group was the most difficult to carry out satisfactorily and the least conclusive. Ovulation did not take place in every case and it was necessary to open the abdomen and make sure of the condition of the ovaries, When ovulation occurred, edema of the vulva and vagina often defeated catheterization. The bladder showed its greatest increase ten days It may be said that the vesical volume was after the injection of antuitrin-R. increased in approximately 50 per cent of the cases. The changes when they did occur were large enough t.o seem to us significant. They are given in Table III. TABLE
111.
PRODGCTION
OF OVVLATION
XORMAL
--__-
-
FIRST CONTROI.
1 2 3 4 5 G 7 s 9 10 11 12
13 14 15
12 14 18 14 12 14 12
18 8
-..-~-___--.SEC'OND C!ONTROI> 10 DAYS LATER 13
18
BY INJEWION RABBITS
__~___ _---
18
12 14
12
iti20
8
10
14 16
12 16
20 28 16 14
18 18
28 8
---. .---~-
THIRD C'OKTROL 20 DAYS LATER 16 1G I4
14 14
OF ANTUITRIN-S
12 8 20 14
30 DAYS LATER
-i
30 2G 34 44 30 28 30 38
? .z .$ 4
ii
40
32
ii
10 18
12
IN
-
54 28
LANQWORTHY-BRACK
:
EFFECT
OF PREZQNANCY
ON
VESICAL
MUSCLE
125
DISCUSSION
We have noticed repeatedly in pregnant cats or in animals which had recently been pregnant that the bladder is capable of holding an unusually large quantity of urine so that these animals are not suitable for studies of disturbances of vesical innervation. In the present experimen.ts we have endeavored to put to a test the effect of pregnancy upon the vesical capacity. When the readings were made the rabbits were deeply anesthetized so that the stretch reflex was no longer active, and fluid escaped only by overflow when the organ had reached the limits of its capacity. By three control readings at ten-day intervals in the normal animals we have demonstrated that the vesical capacity remains relatively constant. Ten days after the animals had been with the male and thereafter through pregnancy and the puerperium the vesical volume was increased. The relationship of the increased vesical volume to changes in the bladder muscle is not established. It seems reasonable to assume that the increased volume is dependent upon decreased tone in the muscle. Microscopic study of the vesical muscle in six animals revealed no significant changes. The question then arose as to whether ovulation produced similar changes. In ovariectomized rabbits the injection of antuitrin-S had no effect upon vesical capacity. It is therefore reasonable to assume that the anterior pituitary-like sex hormone itself has no direct effect on the bladder muscle. Approximately one-half of the adult virgin rabbits showed a significant increase in vesical volume ten days after the injection of antuitrin-S. These results lead us to assume that a substance is elaborated by the corpus luteum which causes a decrease of tone in the vesical muscle. We are not prepared at the present time to hazard an opinion as to which of the corpus luteum hormones, estrin or progestin, this effect on the bladder muscle tone is due. These findings are similar to the changes reported in the ureters in women during pregnancy. They make it appear likely that similar cha:nges occur throughout the length of the urinary tract. Our findings of increased vesical volume following pregnancy confirm the experiments of Woolsey and Brooks. Their results were obtained by quite a different technique. Their findings of diminished volume during estrus or under the influence of progynon-B also lead to the assumption that the sex hormones influence bladder musculature. The fact that proiqynon-B caused a decrease in bladder capacity suggests that the increased capacity noted by us during pregnancy is due to progesterone rather than estrin. REFERENCES
Hundley, J. M., Walton, H. J., Hibbits, J. T., Siegel, L. A., and Bra&, G. B.: AM. J. OBST. & GYNEC. 30: 625, 1935. Kolb, L. C., and Langworthy, 0. R.: J. Pha:rmacol. & Exper. Therap. 63: 198, 1938. Trot, H. F., and MoLane, c. M.: Surg. Gynec. Obst. 62: 65, 1936. Traut, H. F., MoLane, C. M., and Kudner, A. : Surg. Gynec. Obst. 64: 51, 1937. Woolsey, C. N., and Brooks, C. M.: Proc. Am. Physiol. Sot. 49: 167, 1937.
EFFECT
ORTHELLO (From
R.
OF PREGNANCY AND THE CORPUS UPON VESICAL MUSCLE” LANGWORTHY,
the Subdepartment Johns
M.D.,
AND
C.
BERNARD
BALTIMORE, MD. of Neurology and, the Department Hopkins University and Hospital)
BRACK,
LUTEUM M.D.,
of Gynecology,
T
HE innervation of vesical muscle has been studied in this laboratory for several years. It became obvious in the course of the experiments that there were factors other than the nervous stimuli to be considered as influencing vesical activity. We early began to exclude pregnant cats from our series of experimental preparations. The bladder appeared to be capable of holding an unusually large volume of fluid at low pressures. This increased capacity was still present for days or weeks after pregnancy was terminated. The conclusion was reached that the vesical muscle was influenced in its capacity not alone by its nerve supply but also by chemical substances carried in the blood. It has been known for many years that changes in the urinary tract take place with pregnancy. These have been studied particularly in the ureters but have a direct relation to the present experiments. In 1843 Cruveilhier first described dilatation and elongation of the ureter as a frequent accompaniment of the gravid state. He believed that there was a hyperplasia of the tissues composing the walls of the kidney pelvis, the ureter, and the bladder in the form of increased thickness of the muscular and connective tissue elements. In spite of this hypertrophy the lumen of the ureter is dilated. The extent to which these ch,angesappeared varied much in different individuals as well as in the meters of the same individual, the process usually being more marked on the right side. Two explanations for these phenomena have arisen. One group has felt that the pressure of the enlarged uterus upon the ureter at the point where it crosses the pelvic brim was the chief factor. However, larger pelvic tumors than those represented by the pregnant uterus were not often productive of the ureteral changes in the nonpregnant pa.tient. Other authors have suggested an atony of the ureteral musculature. Dilatation of the ureter usually reaches its maximum at about the seventh month of pregnancy, and frequently diminishes toward term despite the enlargement and increasing weight of the uterus. Traut
and McLane (1936) studied contraction waves in the ureters of their The normal ureter of the nonpregnant woman is possessed of rhythmic peristaltic activity which can be measured and recorded. In the majority of patients this rhythmic activity is definitely changed in pregnancy in varying degrees. The altered peristaltic activity is expressed by diminished amplitude of the peristaltic wave commencing in the third month of pregnancy but reaching its peak during the -*Aided by a grant from the Committee on Scientific Research of the American Medical Association.
paitients.
121
122
AMERICAN
JOURNAL
OF
ORSTETRICS
AS0
GYNECOLOGY
seventh and eight months. -1fter the fifth month the number of patients showing diminished ureteral response exceeds those showing normal activity. During thr last month of pregnancy there seems to be a definite ret.unr of muscular irritability as expressed by the measurement of peristalsis and response to stimulation. This diminished peristaltic activity of the ureters seen in pregnancy cannot be explained on the basis of dilatation. on the contrary, dilatation of the uwiers during pegnancy is probably in great part dependcut upon tile ntony of the ureters. Th(? etiology of this ureteral atony during pregneney is, rn the opinion of the authors, not due to any mechanical factor but rather has somet as yet unexplained, chemical basis. Later Traut, MeLane and Kuder ll!):iij pointed uot t,hat the cllaracteristics 01 the ureteral atony are similar in many respects to those affecting the uterino musculature. It -as suggested that the phenomena jn the two organs may have a similar etiology. The ureteral dilat.ation is roughly proportional to the degree of atoay, and both appear and disappear at similar times with regard to the course of pregnancy. Dilatation and atony appear in the third month and are progressivr to the seventh month of pregnancy. During the last two months there is a marked increase in motility, accompanied by n moderate decrease in the dimensions of thr tract. Following delivery atony is again marked until the third week3 subsequent 10 whicah motility returns rapidly to normal level?, which arc usually attained during tllr sixth and seventh weeks post parturn. Dilatation of the tract tlrcreases progresGvelp after delivery and reaches practically the normal vxlucs :Lt the seventh ~4 of the puerperium. Hundley, Walton, Hibbitts, Siegel and Era& (l%!,>) felt that t,he atony of the, ureter must be the result of the activity of hormones elaborated during pregnancy. They found hypertrophy of the muscle, edema, and increased vaseularity in the whole urinarp tract. Other experiments more closely related lo the bladller have beeu performed IJ! i\‘trolsey and Brooks (1937). They placed cats for loug periods in metabolism cages cqnipped with apparatus for recording c~ontinuallp volume and t.ime of mieturition. Micturition volume diminished markedly (luring estrus or while the animal, femaitl Tn the -ftmmk iiw decrease W:LS or male, was under the intlurn~~c of l~r~)~~o~B. Tremendous inrrcasPs in correlated with the vaginal smcnr nncl rstrous c.WlP. micturition rolurnc w\‘Pre observed post paYtuTl1.
chose
to uw
vcrq’
easil\-.
tion. Previously
rabbits
Injection the
This
since
cor~)o~a
Illtea call bc produced
animal norm&c>vulates only nt the of anIuitrin-R also produces ovulation eat 1~s hpcn emplo~etl nlmost esrlnsivel~
in these anituals time of copt11:1iu the rabhit. for our studies
of vesical function. Catheterization of the urethra III the rabbit is difficult because the urethral meatus is well up in the vagina. However it was found possible to introduce a fine glass catheter through the urethra into the bladder of the rabbit and make readings of vesical activity after the same manner which has been employed in cats. The animals were always anesthetized with pentobarbital injected intravenously. Before any further procedures were instituted three control readings at ten-day intervals were made to learn the average vesieal capacity of the animals. If these readings showed little variation, the experiment was continued. In this work we used as the criteria of the experiment any changes from the normal vesical capacity which occurred during pregnancy and following ovulation. Records were made of intravesieal pressure during filling of the bladder; the pressure remained low until the viseus was reaching the limits of its capacity. The normal vesical capacity of an animal under deep anesthesia is remarkably constant as the readings show. Under pentobarbital anesthesia the vesical muscle does not contract reflexly (Eolb and Langworthy, 1938), and urine escapes only by overflow
L&NGWORTHY-BRACK
:
EFFECT
OF
PREGNANCY
ON
VESICAL
MUSCLE
123
when. the intravesical pressure is slowly raised to a point which is rather constant for the individual. The vesieal volume was increased by adding 2 C.C. of fluid at a time until this overflow occurred. Between each introduction of fluid the intravesical pressure was allowed to fall to a resting level. We felt that a demonstration of increased vesical volume developing coincidently with pregnancy suggested an atony of the vesical musculature such as has been shown for the ureters by Tram?. The rabbits did not stand the repeated administration of an anesthetic well and many were lost during the course of the experiments. For the same reason pregnancy The edema of the vagina and vulva subsewas not often carried to its termination. quent to ovulation and during pregnancy was an obstacle to successful catheterization of the urethra. A few animals developed intractable diarrhea with loss of weight. During the period of diarrhea the vesical volume was increased. Careful records of the weight If a rabbit was losing weight, it was of the animals were kept from week to week. dropped temporarily from the experiment. In general the changes in weight had no correlation with the results. The weights are recorded in the control series shown in Table I. TABLE
I.
CASTRATED
.__ EXP.
FIRST READIKG VOI..
WT.
1
8
2 3 4 5 6 7 8 9 16
14 26 16 26 26 48 20 40 30
4.5 6.0 5.5 6.5 6.0 5.0 7.0 4.75 3.5 4.5
__-
lo-DAY INTERVAT, VOI,. WT. 24 5.0 24 6.75 35 WI 22 7.0 18 6.5 S 5.25 26 8.0 3s 6.O 14 4.25 20 5.25 ESPERIMEKTAL
=I I
-
RABBITS ZZ
lo-DAY IKTERV.%L VOL. WT. 12 5.5 24 6.75 44 6.0 10 65 22 6.5 5.5 10 26 6.25 20 6.25 20 5.25 32 G.0
lo-DAY IXTERVAL VOL. WT. ___18 5.25 14 6.5 20 6.25 14 5.25 26 6.75 6 5.0 18 5.75 32 5.75 26 5.5 no I 5.75
OBSERVATIONS
A.. Table I shows the results of a study of ten control animals. The ovaries were removed from the young adult rabbits and they were allowed to recover from the operations. Subsequently a series of four readings of vesical volume was made upon each rabbit at ten-day intervals. After the first three readings the animals were each given 6.2 C.C. of antuitrin-S intravenously. The weight of the rabbit at the time of each reading is given in the chart. According to Dr. Franklin Synder this is sufficient hormone to produce ovulation. It will be observed that the rabbits tended to gain in weight during the progress of the experiment. The readings of vesical volume show only slight variations; ten days after the injection of antuitrin-S no significant changes in vesical volume appeared. II. The changes in vesical volume associated with pregnancy are shown in Table All the rabbits used in the experiments were young virgin females. The II. records are not complete in all the cases due to difficulty in keeping the rabbits alive and in catheterizing the bladder during pregnancy. The three control vesical readings are relatively constant for the single individuals. After the third reading the animal was placed with a male. The next Where pregnancy ensued there was in every reading was made ten days later. case an increase in the vesical volume. The normal volume was in several instances doubled or tripled. Inasmuch as the period of gestation in the rabbit is thirty days it was sometimes poss:ible to make three readings during the period of pregnancy; the results are shown in the tables. As the uterus increased in size there was in certain cases a diminution in the vesical capacity, although the capacity was still much greater than in the nonpregnant animal. Perhaps this was due to mechanical factors pro-
124
AMERICAN TABLE
JOURNAL II.
OF
EFFECT
ORSTRTRICS
OF PREGNANCY.
AND COXTROL
-
ZZ
--
.-
READINGS
__--
2 ODAYR' IT.
(
QYNECOLOQY
ODAYE IlATER
1LATER
10 DAYS FOLLOWING DELIVERY
;E iODAYE IATER _.--
-I_ 56 40
34 46
40 5G 36 34 24 32 ::4 ‘> . .,(I 24 28
58 “4
1
34 50
I I I ! i /
duced by the pressure of the gravid uterus. In other cases the bladder capacity continued to increase through the period of pregnancy. Following the termination of pregnancy the vesical volume was greater than at any previous period. It appeared that the bladder was free from any pressure from the uterus and could expand t,o the limits of its capacity. The bladder remained of large volume for three or four weeks following the termination of pregnancy, and it was only at the end of this time that it returned to its normal volume. C. The final series of experiments had to do with the production of ovulation in the normal rabbit by the injection of antuitrin-S. This group was the most difficult to carry out satisfactorily and the least conclusive. Ovulation did not take place in every case and it was necessary to open the abdomen and make sure of the condition of the ovaries, When ovulation occurred, edema of the vulva and vagina often defeated catheterization. The bladder showed its greatest increase ten days It may be said that the vesical volume was after the injection of antuitrin-R. increased in approximately 50 per cent of the cases. The changes when they did occur were large enough t.o seem to us significant. They are given in Table III. TABLE
111.
PRODGCTION
OF OVVLATION
XORMAL
--__-
-
FIRST CONTROI.
1 2 3 4 5 G 7 s 9 10 11 12
13 14 15
12 14 18 14 12 14 12
18 8
-..-~-___--.SEC'OND C!ONTROI> 10 DAYS LATER 13
18
BY INJEWION RABBITS
__~___ _---
18
12 14
12
iti20
8
10
14 16
12 16
20 28 16 14
18 18
28 8
---. .---~-
THIRD C'OKTROL 20 DAYS LATER 16 1G I4
14 14
OF ANTUITRIN-S
12 8 20 14
30 DAYS LATER
-i
30 2G 34 44 30 28 30 38
? .z .$ 4
ii
40
32
ii
10 18
12
IN
-
54 28
LANQWORTHY-BRACK
:
EFFECT
OF PREZQNANCY
ON
VESICAL
MUSCLE
125
DISCUSSION
We have noticed repeatedly in pregnant cats or in animals which had recently been pregnant that the bladder is capable of holding an unusually large quantity of urine so that these animals are not suitable for studies of disturbances of vesical innervation. In the present experimen.ts we have endeavored to put to a test the effect of pregnancy upon the vesical capacity. When the readings were made the rabbits were deeply anesthetized so that the stretch reflex was no longer active, and fluid escaped only by overflow when the organ had reached the limits of its capacity. By three control readings at ten-day intervals in the normal animals we have demonstrated that the vesical capacity remains relatively constant. Ten days after the animals had been with the male and thereafter through pregnancy and the puerperium the vesical volume was increased. The relationship of the increased vesical volume to changes in the bladder muscle is not established. It seems reasonable to assume that the increased volume is dependent upon decreased tone in the muscle. Microscopic study of the vesical muscle in six animals revealed no significant changes. The question then arose as to whether ovulation produced similar changes. In ovariectomized rabbits the injection of antuitrin-S had no effect upon vesical capacity. It is therefore reasonable to assume that the anterior pituitary-like sex hormone itself has no direct effect on the bladder muscle. Approximately one-half of the adult virgin rabbits showed a significant increase in vesical volume ten days after the injection of antuitrin-S. These results lead us to assume that a substance is elaborated by the corpus luteum which causes a decrease of tone in the vesical muscle. We are not prepared at the present time to hazard an opinion as to which of the corpus luteum hormones, estrin or progestin, this effect on the bladder muscle tone is due. These findings are similar to the changes reported in the ureters in women during pregnancy. They make it appear likely that similar cha:nges occur throughout the length of the urinary tract. Our findings of increased vesical volume following pregnancy confirm the experiments of Woolsey and Brooks. Their results were obtained by quite a different technique. Their findings of diminished volume during estrus or under the influence of progynon-B also lead to the assumption that the sex hormones influence bladder musculature. The fact that proiqynon-B caused a decrease in bladder capacity suggests that the increased capacity noted by us during pregnancy is due to progesterone rather than estrin. REFERENCES
Hundley, J. M., Walton, H. J., Hibbits, J. T., Siegel, L. A., and Bra&, G. B.: AM. J. OBST. & GYNEC. 30: 625, 1935. Kolb, L. C., and Langworthy, 0. R.: J. Pha:rmacol. & Exper. Therap. 63: 198, 1938. Trot, H. F., and MoLane, c. M.: Surg. Gynec. Obst. 62: 65, 1936. Traut, H. F., MoLane, C. M., and Kudner, A. : Surg. Gynec. Obst. 64: 51, 1937. Woolsey, C. N., and Brooks, C. M.: Proc. Am. Physiol. Sot. 49: 167, 1937.