CHAPTER VI._On the mechanism of the physiological action of the cathartics

The Action of Saline Solutions on Loops of Intestine Removed from the

Body.

The fact shown above that local application of saline solutions to the

peritoneal surfaces of the intestine could call forth not only muscular

movements of the intestine, but also an increased secretion, suggested

the possibility of experimenting with loops of intestine entirely

removed from the body. Loops thus isolated are necessarily placed under

new conditions differing entirely from those under which loops normally

connected exist. As mentioned in an early chapter, it was stated by

Claude Bernard that section of the spinal cord below the phrenic causes

active movements to appear in the intestine; and it was later shown by

Pflüger that section of the splanchnic nerves has the same effect, and

stimulation of the peripheral cut ends caused the movements to cease.

It was also noticed by van Braam-Houckgeest that although loops of the

intestine normally connected in the body remained at rest when immersed

in isotonic NaCl solution, active movements appear in the loops when

the splanchnic nerves are cut. Moreau further showed that section of

the mesenteric nerves causes a large increase in the fluid secreted

into the intestine.

I have confirmed these results and have found that loops which are

quiet when the abdomen is opened remain quiet when placed in m/6 NaCl

solution. If, however, loops have become active in any way, through

exposure to the air, or through any stimulation, these movements

continue when the loops are placed in the salt solution. In any case

section of the cervical cord or of the splanchnic nerves, or clamping

of the nerves and bloodvessels supplying the loops, causes a very

marked increase in the peristaltic activity of the loops. In studying

the behavior of isolated loops removed from the body and placed in

various solutions it was therefore necessary to consider the effects

produced by the removal itself.

In describing these experiments, which were made some time ago,[60]

a word may be said as to the methods employed. The rabbits were

anaesthetized with morphine as described before; the abdominal cavity

was opened and the bloodvessels supplying the loop selected were

carefully tied off. Two pairs of ligatures were then placed around the

intestine so that the loop was properly isolated. The intestine was

then cut between each pair of ligatures, and the mesentery divided

between the bloodvessel ligatures and the intestine. In this way the

loop could be taken from the body without injuring it, and without

causing the animal to lose more than a drop or two of blood. The loop

was then emptied by cutting one ligature and allowing the fluid to

drain from that end while it was held up by the ligature of the other

end. The open end was then religatured, and the whole loop suspended in

the solution to be tested. This was arranged so that both ends of the

loop were above the surface of the solution, in order that none of the

solution could by any possibility enter the lumen of the loop through

the ligatured ends. The beakers containing the solutions were kept in

a water bath at 39.5° C. The movements of the loops could in this way

be directly watched, and the amount of fluid secreted in a unit of time

could be easily measured.

If a loop such as has been described above be removed from the

intestine of a rabbit and placed in m/8-m/6 NaCl solution at body

temperature, active movements at once appear. These are regular and

rhythmical, resembling those which set in when the nerves to the

intestine are cut in the uninjured animal. If the loop be allowed

to lie at the bottom of the solution, it will twist and writhe about

in a peculiar worm-like manner. These movements persist in varying

intensity for a considerable time, sometimes as long as an hour,

usually for 40-45 minutes. They disappear gradually. No attempt was

made to obtain a fluid in which the movements could be maintained for

a longer time. These movements are probably merely the continuation of

those always caused by sectioning the nerves to the loop. The m/6 or

m/8 NaCl solution seems to be fairly favorable for their maintenance.

That the loop, however, is not dead when the movements in NaCl cease is

shown by the fact that it can be caused to exhibit active movements by

transferring it to a solution of NaCl containing a small quantity of

BaCl_{2}. It is of course not possible to say that the movements which

appear when the loop is placed in pure NaCl solution are entirely due

to the cutting of the nerves to the loop. It is possible that the NaCl

acts as a direct stimulus and causes the movements to continue.

When a loop is carefully emptied and suspended in a solution of m/8-m/6

NaCl in the way described, it is found that after a considerable time

(20-40 minutes) it is still quite empty. If, on the other hand, an

m/2 solution of NaCl is used the loop is found to contain after 15

to 20 minutes a small but distinct quantity of clear yellowish fluid

resembling the normal intestinal juice. A loop 27 cm. long suspended

in m/2 NaCl for 20 minutes contained 0.6 c.c. fluid. A second loop

30 cm. long in the same solution contained 0.8 c.c. fluid. A control

loop of the same length in m/8 NaCl remained empty. In m/2 NaCl the

movements of the loop are spasmodic and the contractions very strong.

The movements do not usually last more than 5 minutes, although the

loop may be removed from this solution 15 minutes after the movements

have ceased, and may be caused to move again by immersing it in m/8

NaCl containing ¹⁄₂₅ of its volume of m/8 BaCl_{2}. This shows that

the loop is not actually killed by the strong NaCl solution.

A loop suspended in m/6 sodium citrate solution showed active

peristaltic movements, lasting for 20 to 30 minutes. No fluid, however,

collected in this loop. When suspended, however, in m/2 sodium citrate

a measurable quantity of fluid was obtained after 20 minutes. A similar

result was obtained with Na_{2}SO_{4}, active peristalsis, but no

secretion being caused in an m/6 solution. In an m/2 solution, however,

a considerable quantity of fluid collected in the loop.

A loop 28 cm. long suspended in m/8 NaF exhibited active peristaltic

movements which continued for less than 10 minutes. At the end of 20

minutes the loop was found to contain 0.8 c.c. of a clear but slightly

blood-stained fluid.

Loops suspended in m/6 NaCl containing m/6 or m/8 BaCl_{2} in

the proportion of 50 to 1 or 70 to 1 showed very strong muscular

contractions and a well marked secretion of fluid. The muscular

movements were characteristic of barium. Violent local contractions and

firm constrictions of the intestine together with strong peristaltic

movements took place. The loops always contained a distinct and

measurable quantity of fluid after being suspended in this fluid, as

may be seen in the table which follows.

Loops placed in m/6 CaCl_{2} showed no muscular movements whatever,

nor did any fluid gather in the lumen. This is in marked contrast to

the behavior of the loops in the solutions already described. In equal

parts of m/6 NaCl and m/6 CaCl_{2} no movements or secretion took place.

The results of a number of these experiments may be observed in the

following table:--

=======================================================================

| |Concentration| | of | movements | of

---+-------+-------------+-----------+------+----------------+---------

1 | NaCl | m/8 | 40 min. |30 cm.| Active | 0.0

| | | | | 40 min. |

| | | | | |

2 | ” | ” | 20 ” |23 ” | Active | 0.0

| | | | | 40 min. |

3 | ” | m/2 | 20 ” |30 ” | contractions | 0.8 c.c.

| | | | | 5 min. | clear

4 | ” | ” | 20 ” |30 ” | contractions | 0.6 c.c.

| | | | | 5 min. | clear

---+-------+-------------+-----------+------+----------------+---------

5 | Sod. | m/8 | 20 ” |20 ” | Active | 0.0

| Cit. | | | | peristalsis |

| | | | | 20 min. |

| | | | | |

6 | ” | m/2 | 20 ” |32 ” | Violent | 0.4 c.c.

| | | | | 2-3 min. | yellow

---+-------+-------------+-----------+------+----------------+---------

7 |Na₂SO₄ | m/8 | 20 ” |33 ” | Active | 0.0

| | | | | |

8 | ” | m/2 | 20 ” |30 ” | Strong | 1.5 c.c.

---+-------+-------------+-----------+------+----------------+---------

9 | NaF | m/8 | 20 ” |28 ” | Strong | 0.8 c.c.

| | | | | 10 min. | bloody.

---+-------+-------------+-----------+------+----------------+---------

10 |{NaCl |m/8-70 c.c.} | 20 ” |25 ” |Active mov’m’ts.| 0.6 c.c.

|{BaCl₂ |m/8-1 c.c. } | | | | clear

| | | | | |

11 | ” | ” | 20 ” |46 ” |Active mov’m’ts.| 0.8

| | | | | | c.c.

| | | | | |

12 | ” | ” | 20 ” |60 ” |Active mov’m’ts.| 1.2

| | | | | | c.c.

| | | | | |

13 | ” | ” | 20 ” |31 ” |Active mov’m’ts.| 1.2

| | | | | | c.c.

| | | | | |

14 |{NaCl |m/8-50 c.c.} |1st 20 min.|63 ” |Active mov’m’ts. | 1.6

| | | | | | c.c.}

|{BaCl₂ |m/8-1 c.c. } |2nd 20 ” | | | 0.2

| | | | | | c.c.}

| | | | | |

15 | BaCl₂ |m/8-50 c.c.} |1st 20 min.|32 ” | Violent | 2.7

| | | | | contractions. | c.c.}

| | |2nd 20 min.| | | 0.2

| | | | | | c.c.}

| | | | | |

16 |{NaCl |m/8-30 c.c.} | 20 min. |23 ” | Violent | 0.9

|{BaCl₂ |m/8-30 c.c.} | | | contractions. | c.c.

| | | | | |

17 | CaCl₂ | m/8 | 20 ” |20 ” | None | None

| | | | | |

18 | ” | ” | 20 ” |15 ” | ” | ”

| | | | | |

19 |{CaCl₂ |m/8-50 c.c.} | 20 ” |10 ” | ” | ”

|{NaCl |m/8-50 c.c.} | | | |

| | | | | |

20 |{CaCl₂ |m/2-50 c.c.} | 20 ” |15 ” |Slight movements| ”

|{NaCl |m/2-50 c.c.} | | | not peristaltic|

| | | | | |

21 |{CaCl₂ |m/1-50 c.c.} | 20 ” |15 ” |Slight movements| Slight

|{NaCl |m/1-50 c.c.} | | | not peristaltic| trace.

| | | | | |

22 |{NaCl |m/8-30 c.c.} | 20 ” |35 ” | Irregular | None.

|{BaCl₂ |m/8-1 c.c. } | | | contractions |

|{CaCl₂ |m/8-30 c.c.} | | | not strong |

| | | | | |

23 |{NaCl |m/8-30 c.c.} | 20 ” |30 ” | Irregular | 0.2

|{BaCl₂ |m/8-1 c.c. } | | | contractions, | c.c.

|{CaCl₂ |m/8-30 c.c.} | | | not strong |

| | | | | |

24 |{BaCl₂ |m/8-1 c.c. } | 20 ” |30 ” | Irregular | 0.2

|{CaCl₂ |m/8-50 c.c.} | | | contractions. | c.c.

---+-------+-------------+-----------+------+----------------+---------

It is interesting to note again here that the secretion into these

loops is almost uniformly inhibited by the presence of calcium. When

barium is also present in the solution this inhibition is only partial.

The action of barium is never entirely counteracted by calcium chloride.

The experiments further show that the saline purgatives act on the

intestine not only when it has its normal position and connections

with the rest of the body, but also when it is entirely isolated. This

eliminates in the first place the possibility of the solutions acting

entirely through the central nervous system. It is possible that the

salts have some influence on the central nervous system, but from these

experiments it seems probable that their main action is either on

the glandular and muscular tissues themselves, or on the plexuses of

Auerbach and Meissner in the intestinal walls.

As I have already shown, the action of a saline purgative on the

intestine consists of two parts, the increase of the peristaltic

activity and the increase of the amount of fluid secreted into the

lumen; or, in other words, the action on the muscle and the action on

the glandular tissue. In the experiments just described it is clear

that these two separate actions exist side by side. For example, m/8

solutions of sodium chloride, citrate, or sulphate cause well marked

peristaltic movements or allow these to continue, while no secretion

of fluid takes place. Stronger solutions of these salts, on the other

hand, such as m/2 produce a distinct secretion. Thus a concentration

of a salt which is sufficient to produce muscular activity may not

be sufficient to affect the glandular tissues. One is tempted to

conclude that in the intestine it requires a stronger stimulus to

produce secretory activity than it does to cause muscular movements.

It is possible that this is true, but the anatomical relations also

must be taken into consideration. The muscle coats lie immediately

under the thin peritoneal layer through which the salts are absorbed;

and it seems probable that in the experiments described the solutions

reached the muscle more easily and rapidly than they could the

glandular tissue which is situated on the other side of the muscular

and submucous layers. Further, it must be noticed that the movements

seen in m/8 NaCl may be merely the continuation of those caused by

separation of the loop from the central nervous system.

The amount of fluid which may be secreted by a loop of intestine

isolated from the body is limited by the absence of the blood supply.

The loop, as shown above, secretes a certain amount of fluid in the

first 10 or 20 minutes. If it is then emptied, usually no more fluid

appears. The quantity secreted depends on the amount of fluid contained

in the intestinal walls at the time of its removal from the body. No

fluid passes from the solution in which the loop is suspended into the

lumen of the loop; no current is established through the walls from the

outside inwards. It seems possible to supply the stimulus for secretion

in the solution in which the loop is suspended; but it is not possible

in this way to renew the fluid which the glands have secreted into the

lumen. This can apparently be done only through the blood vessels.

FOOTNOTES:

[60] MACCALLUM, J. B.: University of California Publications,

Physiology, Vol. I, 1904, p. 115.

On the mechanism of the physiological action of the cathartics · 第 6 / 11 章