The Action on the Intestine of Solutions Containing Two Salts.
As stated above, it was shown by Claude Bernard and by Pflüger that
section of the spinal cord below the phrenic nerve, or section of
the splanchnic nerves, causes a marked increase in the intestinal
movements, and also an increase in the amount of fluid secreted
(Moreau). These movements continue in loops isolated and removed from
the body and placed in m/6 NaCl, LiCl, Na_{2}SO_{4}, sodium citrate,
etc., for varying periods of time. They continue far longer in NaCl
than in any other solution. Calcium chloride inhibits these movements,
as is the case also with magnesium chloride. It was found,[61] however,
in making these experiments with isolated loops removed from the body,
that with certain mixtures of NaCl or LiCl with CaCl_{2} or MgCl_{2},
movements began after 20 or 25 minutes of a character differing
entirely from the movements seen in pure NaCl. An idea of this
phenomenon may be gained from the following description of experiments.
A word may be first said with regard to the methods used in these
experiments. In rabbits anaesthetized as usual, the abdomen was opened
and a loop 30-40 cm. in length isolated by ligatures. By means of a
needle and thread the blood vessels supplying the loop were carefully
tied and the loop rapidly excised. It was then cut into a number of
pieces, usually four, which were transferred with as little handling
as possible to the beakers containing the solutions to be tested.
These beakers were kept in a water bath at 39.5° C. It is desirable in
these experiments to use loops which contain no faeces, since unknown
substances in the faeces might go into solution and disguise the action
of the salt being tested. For this reason the upper part of the small
intestine was principally used since in the rabbit it is usually empty
or can be readily emptied. In each set of experiments the loops must
all come from the same rabbit, for there exist considerable differences
in irritability in different animals. On account of these differences
it is necessary to have control experiments in the case of each rabbit.
Loops also which have been unduly exposed to the air cannot be used.
It is of great importance to keep the solutions at a constant body
temperature.
_(a) LiCl and CaCl_{2}._ A loop of intestine removed from the body and
placed in an m/6 LiCl solution at body temperature usually exhibits
only slight movements, which soon cease. This seems to vary somewhat
with different rabbits. In some cases the loop shows no movements at
all, while in other instances it moves regularly for half a minute
and then comes to rest in the solution. These movements are quiet and
regular and resemble those described in loops immersed in m/6 NaCl
solution. When a loop has ceased to move it does not become active
again. In exceptional cases these movements may last 5-10 minutes, but
rarely longer. The LiCl solution seems less favorable for the long
duration of the movements than the NaCl.
A loop similarly immersed in m/6 CaCl_{2} solution at body temperature
remains in the great majority of cases quite motionless from the first.
In some instances slight movements appear immediately after it is
placed in the solution, but these soon disappear. After 25-40 minutes
it is not uncommon to see the loop slowly straighten out, and at the
end of this time the length of the loop is much less than it was at
first. This seems to be due to a slow contraction of the longitudinal
muscle layer, so slow that no movement can be observed. A difference
is seen also in the shape of the loops placed in LiCl and in CaCl_{2}.
The former after it comes to rest is practically its original length
and is coiled up in a circle; the latter is about half its original
length and is almost straight.
A loop similar to the above placed in 50 c.c. m/6 LiCl + 5 c.c. m/6
CaCl_{2} behaves in a manner entirely different from loops from the
same animal placed in either LiCl or CaCl_{2} alone. On being first
immersed in the mixture it exhibits practically no movements. Even in
cases where the control loop is active at first the corresponding loop
in the mixture of LiCl and CaCl_{2} shows no movements. It remains
perfectly quiet for 10-15 minutes. Then sharp constrictions appear
here and there in the loop. These are followed a second or two later
by violent contractions which cause the loop to coil upon itself in a
most active manner. These contractions somewhat resemble those caused
by BaCl_{2} in the intact intestine. They follow one another rapidly
so that the loop is turned and twisted tightly upon itself. This
extreme activity persists for 30-45 minutes, sometimes for an hour,
while during all this time the control loops in LiCl and in CaCl_{2}
are entirely motionless. These movements are not at all of the same
character as those which may appear at the beginning in pure LiCl
solution, and could not be considered as these same movements delayed.
Such an experiment is outlined in the following table:--
Time.
Loops 50 c.c. m/6 LiCl 50 c.c.
placed in 50 c.c. m/6 LiCl + 5 c.c. m/6 m/6 CaCl_{2}
solutions at CaCl_{2}
10:05 no movements no movements no movements
10:10 no movements no movements no movements
10:15 no movements no movements no movements
10:19 no movements violent movements begin no movements
10:25 no movements very active movements no movements
10:30 no movements very active movements no movements
10:45 no movements very active movements no movements
10:50 no movements movement less active no movements
11:00 no movements movement very slight no movements
11:15 no movements movement almost stopped no movements
11:20 no movements no movements no movements
By varying the proportions of LiCl and CaCl_{2} the results may be
somewhat changed. The characteristic contractions may be obtained with
as small a quantity of CaCl_{2} as in a mixture of 50 c.c. m/6 LiCl +
¹⁄₂ c.c. m/6 CaCl_{2}. The movements, however, last only 5-10 minutes
and are less active than in a mixture of 50 LiCl + 5 CaCl_{2}. This
latter mixture seems to be perhaps the most favorable, although almost
equally powerful contractions are obtained with mixtures containing
as much as 10 c.c. CaCl_{2} to 50 c.c. LiCl. When more CaCl_{2} than
this is added the movements usually appear later and last a much
shorter time. With equal parts of LiCl and CaCl_{2} they cease in 15
to 20 minutes, while in a mixture of 5 c.c. LiCl + 50 c.c. CaCl_{2}
the movements appear late and last only 4 or 5 minutes. The loops
in mixtures with relatively much CaCl_{2} come to rest in the shape
characteristic of loops in pure CaCl_{2}. They become shortened and
are found to be straightened out at the end of the experiment. Where
relatively much LiCl is present the loops remain almost their original
length and are usually coiled. This is shown in the following table:--
50 c.c. Li Cl 50 c.c. CaCl_{2}
Time 50 c.c. LiCl + + 50 c.c. CaCl_{2}
5 c.c. CaCl_{2} 5 c.c. LiCl
11:14 Length of loop Length of loop Length of loop Length of loop
10 cm. 10 cm. 10 cm. 10 cm.
11:14 no movements no movements no movements no movements
11:20 no movements very active no movements no movements
movements
11:35 no movements very active movements no movements
movements begin
11:40 no movements very active Movements no movements
movements slow
11:50 no movements very active no movements no movements
movements
12:00 no movements very active no movements no movements
movements
12:05 no movements no movements no movements no movements
12:10 Length about Length about Length about Length about
8 cm. 8 cm. 4 cm. 4 cm.
These muscular contractions which appear in mixtures of LiCl and
CaCl_{2}, and do not appear in either LiCl or in CaCl_{2} alone, are
not the continuation of movements caused by separating the loop from
the central nervous system. These latter movements which are sometimes
seen for a short time following the immersion of the loop in pure LiCl
solution are inhibited by CaCl_{2}. Further, the movements which come
on later in mixtures of LiCl and CaCl_{2} are of entirely different
character, being convulsive and violent and many times more powerful
than any movements seen in pure LiCl. If they were the movements seen
in pure LiCl, only delayed by the CaCl_{2}, they should be more active
in solutions containing the least CaCl_{2}. This is not the case,
since in a mixture of 50 c.c. LiCl + ¹⁄₂ c.c. CaCl_{2} they are by
no means so active as in 50 c.c. LiCl + 5 c.c. CaCl_{2}. A further
experiment shows this still more clearly. A loop placed in 50 c.c. m/6
LiCl was allowed to come to rest, and was left in the solution for 10
minutes. No movements whatever were to be seen at this time. There were
then added 5 c.c. m/6 CaCl_{2} to the LiCl solution containing the
motionless loop. Within one minute the loop became violently active in
the characteristic way described above. This activity continued for
nearly an hour.
In attempting to explain this phenomenon one is tempted to take Loeb’s
suggestion as to the action of calcium in Gonionemus, namely, that
it counteracts the poisonous effect of the sodium chloride. If the
LiCl solution were toxic, however, it is difficult to imagine that
the loop could be restored suddenly to activity as described above by
the addition of a small quantity of CaCl_{2}, after it had lain in
pure LiCl solution for 10 minutes. It is also difficult to consider
calcium as a stimulating agent in this case, since, as shown above, in
all other instances in the intestine it has the opposite action. Also
calcium chloride alone in no concentration causes this phenomenon. The
action of CaCl_{2} in this instance is suggestive of the action of
a catalyser, the addition of which enormously hastens some chemical
reaction. It is possible that the muscular activity in this case
depends on a chemical reaction which is brought about neither by LiCl
nor by CaCl_{2}, but by a combination of these two or perhaps by an
intermediate product.
Whatever may be the explanation of these phenomena, the fact remains,
and is easy of demonstration, that an effect is produced on isolated
loops of intestine by a combination of LiCl and CaCl_{2} which is
entirely different from what can be produced by either LiCl or CaCl_{2}
alone.
(_b_) _NaCl_ + _CaCl_{2}_. The phenomena described above as occurring
when isolated loops of intestine are immersed in mixtures of LiCl and
CaCl_{2} can be produced also in mixtures of NaCl and CaCl_{2}. The
behavior of loops placed in pure CaCl_{2} and in pure NaCl has been
described. In the former the loop remains motionless; in the latter
regular rhythmical movements continue for 40 minutes or more.
When, however, a loop is placed in 50 c.c. m/6 NaCl + 10 c.c. m/6
CaCl_{2} there are no movements whatever to be seen at first. The
loops remains quiet for about 10 minutes. The movements which are seen
from the beginning in the control loop in pure NaCl solution have
apparently been inhibited by the CaCl_{2} present in the mixture.
After 10 minutes, however, the loop gradually becomes very active, and
violent contractions appear which are similar to those described as
taking place in mixtures of LiCl and CaCl_{2}. The loop becomes much
more active than the control loop in pure NaCl. The onset in the LiCl
mixture is more sudden, but otherwise the phenomenon is practically the
same. The movements in NaCl + CaCl_{2} persist for 30 or 40 minutes,
sometimes for an hour. When the concentration of the CaCl_{2} in the
mixture is relatively great this effect is not obtained. This is shown
in the following table:--
Time 50 c.c. NaCl 50 c.c. NaCl 50 c.c. NaCl
+ 5 c.c. CaCl_{2} + 10 c.c. CaCl_{2}
10:35 quite active no movements no movements
10:40 quite active no movements no movements
10:45 quite active slight movements slight movements
10:50 less active slight movements slight movements
10:55 still active very active very active
11:00 still active extremely active extremely active
11:15 still active extremely active extremely active
11:30 almost stopped extremely active extremely active
11:45 no movements movements quieter movements quieter
11:50 no movements no movements no movements
Time 50 c.c. NaCl 50 c.c. NaCl 50 c.c. CaCl_{2}
+ 20 c.c. CaCl_{2} + 40 c.c. CaCl_{2}
10:35 no movements no movements no movements
10:40 no movements no movements no movements
10:45 no movements no movements no movements
10:50 no movements no movements no movements
10:55 no movements no movements no movements
11:00 no movements no movements no movements
11:15 no movements no movements no movements
11:30 no movements no movements no movements
11:45 no movements no movements no movements
11:50 no movements no movements no movements
Thus here also, as in the case of LiCl and CaCl_{2}, there are produced
effects in mixtures of NaCl and CaCl_{2} which cannot be brought about
by either salt alone. The presence of CaCl_{2} seems to inhibit the
movements which are first present in a loop placed in NaCl solution.
When added in small quantities, _e.g._, not more than 10 c.c. m/6
CaCl_{2} to 50 c.c. m/6 NaCl, it produces after an interval of 10-15
minutes very violent movements such as are never seen in pure NaCl
solution nor in pure CaCl_{2}. When, however, it is added in greater
proportion than this, e.g., 20 or more c.c. CaCl_{2} to 50 c.c. NaCl,
all movements are stopped. The explanation of this is no more clear
than the similar occurrence in mixtures of LiCl and CaCl_{2}.
If a loop be placed in a mixture of LiCl and NaCl in equal parts,
movements appear such as are seen in pure NaCl, but do not persist
for so long a time. In the mixture of these two salts no such result
is obtained as has been described in mixtures of LiCl and CaCl_{2} or
of NaCl and CaCl_{2}. Mixtures of CaCl_{2} and MgCl_{2} also produce
no such movements. In these few salts it seems to be a mixture of
chlorides of a monovalent with a bivalent metal which produces the
extreme activity of the loop, while mixtures of chlorides of two
monovalent metals or of two bivalent metals do not bring this about.
FOOTNOTES:
[61] MACCALLUM, J. B.: University of California Publications,
Physiology, Vol. II, 1905, p. 47.