FOOTNOTES:
[60] MacCallum, J. B.: University of California Publications, Physiology, Vol. I, 1904, p. 115.
CHAPTER VII.
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, Na2SO4, 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 CaCl2 or MgCl2, 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 CaCl2. 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 CaCl2 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 CaCl2. 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 CaCl2 behaves in a manner entirely different from loops from the same animal placed in either LiCl or CaCl2 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 CaCl2 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 BaCl2 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 CaCl2 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 placed in solutions at | 50 c.c. m/6 LiCl | 50 c.c. m/6 LiCl + 5 c.c. m/6 CaCl2 | 50 c.c. m/6 CaCl2 |
|---|---|---|---|
| 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 CaCl2 the results may be somewhat changed. The characteristic contractions may be obtained with as small a quantity of CaCl2 as in a mixture of 50 c.c. m/6 LiCl + ¹⁄₂ c.c. m/6 CaCl2. The movements, however, last only 5-10 minutes and are less active than in a mixture of 50 LiCl + 5 CaCl2. 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. CaCl2 to 50 c.c. LiCl. When more CaCl2 than this is added the movements usually appear later and last a much shorter time. With equal parts of LiCl and CaCl2 they cease in 15 to 20 minutes, while in a mixture of 5 c.c. LiCl + 50 c.c. CaCl2 the movements appear late and last only 4 or 5 minutes. The loops in mixtures with relatively much CaCl2 come to rest in the shape characteristic of loops in pure CaCl2. 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:—
| Time. | 50 c.c. LiCl | 50 c.c. LiCl + 5 c.c. CaCl2 | 50 c.c. CaCl2 + 5 c.c. LiCl | 50 c.c. CaCl2 |
|---|---|---|---|---|
| 11:14 | Length of loop 10 cm. | Length of loop 10 cm. | Length of loop 10 cm. | Length of loop 10 cm. |
| 11:14 | no movements | no movements | no movements | no movements |
| 11:20 | no movements | very active movements | no movements | no movements |
| 11:35 | no movements | very active movements | movements begin | no movements |
| 11:40 | no movements | very active movements | Movements slow | no movements |
| 11:50 | no movements | very active movements | no movements | no movements |
| 12:00 | no movements | very active movements | no movements | no movements |
| 12:05 | no movements | no movements | no movements | no movements |
| 12:10 | Length about 8 cm. | Length about 8 cm. | Length about 4 cm. | Length about 4 cm. |
These muscular contractions which appear in mixtures of LiCl and CaCl2, and do not appear in either LiCl or in CaCl2 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 CaCl2. Further, the movements which come on later in mixtures of LiCl and CaCl2 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 CaCl2, they should be more active in solutions containing the least CaCl2. This is not the case, since in a mixture of 50 c.c. LiCl + ¹⁄₂ c.c. CaCl2 they are by no means so active as in 50 c.c. LiCl + 5 c.c. CaCl2. 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 CaCl2 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 CaCl2, 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 CaCl2 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 CaCl2, 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 CaCl2 which is entirely different from what can be produced by either LiCl or CaCl2 alone.
(b) NaCl + CaCl2. The phenomena described above as occurring when isolated loops of intestine are immersed in mixtures of LiCl and CaCl2 can be produced also in mixtures of NaCl and CaCl2. The behavior of loops placed in pure CaCl2 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 CaCl2 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 CaCl2 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 CaCl2. 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 + CaCl2 persist for 30 or 40 minutes, sometimes for an hour. When the concentration of the CaCl2 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 + 5 c.c. CaCl2 | 50 c.c. NaCl + 10 c.c. CaCl2 | 50 c.c. NaCl + 20 c.c. CaCl2 | 50 c.c. NaCl + 40 c.c. CaCl2 | 50 c.c. CaCl2 |
|---|---|---|---|---|---|---|
| 10:35 | quite active | no movements | no movements | no movements | no movements | no movements |
| 10:40 | quite active | no movements | no movements | no movements | no movements | no movements |
| 10:45 | quite active | slight movements | slight movements | no movements | no movements | no movements |
| 10:50 | less active | slight movements | slight movements | no movements | no movements | no movements |
| 10:55 | still active | very active | very active | no movements | no movements | no movements |
| 11:00 | still active | extremely active | extremely active | no movements | no movements | no movements |
| 11:15 | still active | extremely active | extremely active | no movements | no movements | no movements |
| 11:30 | almost stopped | extremely active | extremely active | no movements | no movements | no movements |
| 11:45 | no movements | movements quieter | movements quieter | no movements | no movements | no movements |
| 11:50 | no movements | no movements | no movements | no movements | no movements | no movements |
Thus here also, as in the case of LiCl and CaCl2, there are produced effects in mixtures of NaCl and CaCl2 which cannot be brought about by either salt alone. The presence of CaCl2 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 CaCl2 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 CaCl2. When, however, it is added in greater proportion than this, e.g., 20 or more c.c. CaCl2 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 CaCl2.
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 CaCl2 or of NaCl and CaCl2. Mixtures of CaCl2 and MgCl2 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.