THE REACTION OF THE CAT’S UTERUS TO

STROPHANTHUS AND CALCIUM

FRED RANSOM
The Pharmacological Laboratory, London (Royal Free Hospital) School of Medicine
for Women, University of London

Received for publication January 5, 1920

It has been shown that strophanthus as well as certain other

drugs have their characteristic effect upon the frog’s heart even
when Ca is absent from the perfusing fluid, and Loewi (1) has
called attention to the strong resemblance between the action
of digitalis and that of Ca on the frog’s heart, and has suggested
that the drug sensitizes the cardiac muscle to Ca. It appeared
therefore interesting to ascertain whether an ordinary unstriped
muscle suspended in a medium containing no Ca would respond
to strophanthus in the same way as the heart muscle of the frog.
For the purpose of these experiments the uterine muscle of the
cat was selected.
METHOD

Pieces of cat’s uterus were suspended in warm oxygenated

Ringer’s solution or in a Ringer modified in so far as it was
made up without Ca (R-Ca); to either of these Tinct. Strophanthi
was added so as to give 0.5 per cent. In the following tracings
the upstroke of the writing lever represents contraction of the
muscle. The immersion fluid was changed or renewed at
intervals of about five minutes and the spaces between the
letters on the tracings corresponds roughly to this period.
When a piece of uterus which is executing rhythmic move-
ments in Ringer’s solution is transferred to a Ringer modified
by the omission of Ca (R-Ca), the movements are either dimin-
ished or cease altogether, on substituting ordinary Ringer the
movements return, and if now the Ringer is replaced by R-Ca
the movements again cease (fig. 1).
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THE JOUR. OF PHARM. AND EXPER. THERAP., VOL. XV, NO. 3

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 REACTION OF UTERUS TO STROPHANTHUS AND CALCIUM 183

As is already known, strophanthus acts upon uterine and

other plain muscle as upon the cardiac muscle, causing increase
in range of movements and in tone (fig. 2). If the uterine
movements have been checked by immersion in R-Ca, the
addition of strophanthus to the R-Ca causes a very marked
increase in range of movement and a rise of tone. On replacing
the R-Ca plus strophanthus by R-Ca, the movements are again
diminished though the tone remains high, substitution of
Ringer plus strophanthus (S R) for the R-Ca causes a further

S.

FIG. 2. S FOR TINcT. STROPHANTHI 0.5 PER CENT IN RINGER’S SOLUTION

marked rise in tone which is apparently due to the combined

action of strophanthus and Ca (fig. 3). The uterine movement
having been arrested by immersion in R-Ca and started again
by adding strophanthus, the substitution of plain Ringer for R-Ca
plus strophanthus has a very marked effect in increasing move-
ment, some rise of tone occurring at the same time (fig. 4). The
muscle appears to have become extraordinarily susceptible to
Ca; this may be well seen on comparing figure 1 with figure 4,
in the former case, in which the muscle had not been subjected
to strophanthus, the substitution of Ringer for R-Ca had much
184 FRED RANSOM

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 REACTION OF UTERUS TO STROPHANTHUS AND CALCIUM 185

less effect than when, figure 4, the muscle had previously been
under the influence of the drug.
If after depression in R-Ca followed by exposure to strophan-
thus in the same medium for five minutes the uterus is replaced
in R-Ca, in order to wash away the drug, and then in plain
Ringer, renewing the latter every five minutes, there is a very
marked effect, each succeeding renewal of the Ringer increasing
the muscular tone (fig. 5). The inference is that the strophanthus
makes the muscle extraordinarily sensitive to Ca and the result

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FiX. 4. R-Ca FOR RINGER’S SOLUTION WITHOUT Ca; S FOR TINCT. STROPLIANTHI
0.5 PER CENT IN R-Ca; R FOR RINGER’S SoLUTIoN

is the more striking since the strophanthus was only applied for
five minutes and was not present in the final application of
Ringer.
The need for Ca and the effects of its absence or removal on
muscle are common knowledge. The above experiments show
further that as with the heart so also with the uterine muscle
strophanthus will restore the muscular activity in the absence
of Ca. It appears to depend upon the strength of the stro-
phanthus solution and the length of its application whether the
therapeutic action will be followed by toxic effects or not.
186 FRED RANSOM
 REACTION OF UTERUS TO STROPHANTHUS AND CALCIUM 187

In so far as the uterus is concerned this therapeutic action of

strophanthus may have some practical bearing in the following
way: during pregnancy the mother has to furnish a very large
quantity of Ca for the building up of the foetal tissues, but
there is at present no evidence that the normal Ca-content of
the blood is altered in pregnancy, indeed the experiments of
Jansen (2) go to show that this is not the case. A pregnant
woman then, living upon a diet poor in Ca, would have to supply
the excess Ca from her own tissues, from bones perhaps chiefly
but not improbably other structures also would lose Ca. In
this respect it is interesting to note that L. Zuntz (3) has found
that if pregnant rats were kept for the duration of the pregnancy
upon a diet poor in Ca the offspring did not appear to suffer,
certainly the per cent Ca-content of the foetus was not dimin-
ished; on the other hand if the rats were kept for some time
before and during pregnancy on such a diet the development of
the foetus was injuriously affected. Do these results perhaps
indicate that there is normally a certain reserve of Ca which
can be safely drawn upon to some extent but that any further
withdrawal acts injuriously upon tissues formed during the
drain? If so the uterine muscle which is built up during
pregnancy might be more or less inefficient, perhaps from an
abnormally low Ca-content, in a woman living upon a diet
poor in Ca, and such an inefficient muscle would tend to favor
the occurrence of post-partum hemorrhage. The experiments
recorded above suggest that in such an event the intravenous
injection of strophanthin might be useful by increasing the
tone and favoring the contraction of the uterus.

SUMMARY

The movements of the excised cat’s uterus, which have been

diminished or arrested by placing it in a Ringer’s fluid contain-
ing no Ca, are restored and usually increased by the addition of
strophanthus.
The effect of quite a short exposure of uterine muscle to stro-
phanthus is to make it extraordinarily responsive to Ca.
188 FRED RANSOM

It is suggested that some forms of post-partum hemorrhage

may be due to subsistence upon a diet poor in Ca affecting the
efficiency of the uterine muscle and that in such cases strophan-
thin might be usefully injected intravenously.

REFERENCES

(1) LoEwl: Muenchen. med. Wochenschr., 1917, p. 1003.

(2) JANSEN: Deutech. Arch. f. kim. Med., cxxv, 1918, p. 168.
(3) ZUNTZ, LEO: Arch. f. Gynaekoi. 1100, 1919, p. 244.