EFFECTS OF VARIOUS COLLOIDS AND OTHER

AGENTS WHICH PRODUCE ANAPHYLACTOID PilE-

NOMENA ON SURVIVING INTESTINE AND UTERUS’

PAUL J. HANZLIK
Prom the Pharmacological Laboratory, School of Medicine, Western Reserve Uni-
versity, Cleveland

Received for publication, October 31, 1919

OBJECT

All the evidences that have been thus far obtained by us

(1, 2, 3) indicate that the marked inflation of the intact and
surviving lungs, produced by agar is not due to direct stimu-
lation of bronchial muscle or parasympathetic endings. The
effects of various other non-protein colloids are variable, though
quite similar with some, notably acacia. The mechanism of
action of these agents was discussed in a previous communica-
tion. However, in order to make the proof against smooth
muscle stimulation by these agents still more conclusive,
experiments have been made on surviving intestine and uterus.

METHODS

The surviving intestine (longitudinal and circular strips) of

rabbits and guinea-pigs and longitudinal strips of rabbit’s virgin
uterus were used. The strips were conveniently attached to
weighted levers, which recorded the movements of the organs on
a slow moving kymograph. For immersion, 50 cc. of Ringer’s
solution (mammalian) was used in tall glass cylinders resting in
a large water bath maintained at 38#{176}C.The various agents
were added after peristalsis was fairly constant.
‘This investigation was supported in part by a grant from the Therapeutic
Research Committee of the Council on Pharmacy and Chemistry of the American
Medical Association.
463
 464 PAUL 3. HANZLIK

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 EFFECTS OF COLLOIDS ON INTESTINE AND UTERUS 465

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TES JOUR. O PRARM. AND RXPRR. THREAP., VOL. XIV, NO. S

466 PAUL J. HANZLIK

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 EFFECTS OF COLLOIDS ON INTESTINE AND UTERUS 469

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Fia. 1. EXPERIMENT 167

Showing effects of agar (1 per cent), acacia (1.7 per cent), starch (1.2 per
cent), glycogen (0.1 per cent), aithea (2 per cent), dextrin (1.2 per cent), gelatin
(1.2 per cent), nuclein solution (1 cc. = 0.02 per cent), peptone (1 per cent), and
rabbit’s serum (0.2 per cent) on surviving rabbit’s uterus in Ringer’s solution
(50 cc.). The figures in parentheses denote end concentrations. Time: each
stroke = 5 seconds. Depression was produced by all agents except peptone and
rabbit’s serum which actcd as controls and stimulated uterine persistalsis.
 EFFECTS OF COLLOIDS ON INTESTINE AND UTERUS 475

The concentrations of the different agents varied. These

ranged from concentrations occurring in blood after the intra-
venous injection of these in the experiments on systemic actions
previously reported (1, 2) up to very high concentrations in
order to see if augmentor effects could be obtained.
None of the animals had been previously treated with any of
the agents used. The experiments on rabbit’s uterus agreed so
closely with those on the intestine of both rabbit and guinea-pig
that it was deemed unnecessary to carry out additional experi-
ments with guinea-pig’s uterus.

FIG. 2. EXPERIMENT 166

Showing effects of agar (1 per cent), acacia (2 per cent), nuclein solution (0.02
per cent), congo red (0.2 per cent), peptone (0.2 per cent), beef serum (4 per
cent), and neutral althea (2 per cent) on longitudinal strip of rabbit’s intestine
in Ringer’s solution (50 cc.). The figures in parentheses denote end concentra-
tions. Depression was produced by agar, acacia, nuclein solution, and gelatin;
stimulation by peptone, beef serum, congo red and neutral altrea.

Fio. 3. EXPERIMENT 165

Showing effects of rabbit’s serum (0.2 per cent), horse serum (0.2 per cent),
and glycogen (0.1 per cent) on longitudinal strip of rabbit’s intestine in Ringer’s
solution (50 cc.). The figures in parentheses denote end concentrations of the
different agents. Depression was produced by horse serum and glycogen; stimu-
lation by rabbis’s serum.
 476 PAUL 3. HANZLIK

RESUI/rS

The results with surviving intestine are presented in table 1,

and those with uterus in table 2. These indicate also the
various concentrations that were used and conditions under
which the experimentswere performed. In addition, three figures,
illustrating typical effects of the more important agents on the
intestine and uterus, are included.
The results (as indicated by the data in the tables, and the
figures) are so uniform and striking that further interpretation is
practically unnecessary.

SUMMARY

The main results may be stated as follows:

Agar produces no effects on or
depressionslight of the pen-
stalsis of surviving intestine and uterus.
The following agents
uniformly depressed both the intestine and uterus; acacia, dex-
tm, glycogen, gelatin, starch, human and horse serums and
nuclein solution (Abbott). Althea extract was variable, al-
though depression was the rule, no matter whether slightly acid,
alkaline or neutral in reaction. The following agents produced
moderate to marked stimulation of both uterine and intestinal
penistalsis; peptone, congo red and rabbit’s serum. Beef serum
was irregular. So far as peptone and rabbit’s serum are con-
cerned the results obtained are confirmative of the usual effects,
and these agents served as controls for the inactive agents, indi-
cating that the organs were functionally active and responsive
in the usual way when tested against well known augmentors of
peristalsis. The results with congo red do not agree with those
on surviving lungs in which inflation (bronchoconstniction) did
not occur. However, this is immaterial to the results of this
investigation.
So far as agar, acacia and the remaining non-protein colloids
are concerned, the results confirm those obtained on surviving
- lungs. That is, these agents are not stimulants of plain muscle
in the bronchi, uterus and intestine. On the contrary, they
almost invariably depressed the intestinal and uterine muscle.
 EFFECTS OF COLLOIDS ON INTESTINE AND UTERUS 477

This would be generally expected with colloids, that is, a limi-

tation of physiological activity because of their peculiar physical
chemical properties (lessened diffusion and dissociation of ions,
adsorption, etc.) with effects on nutrition.
As far as acacia is concerned, my results are confirmative of
a preliminary report by Kruse (4). Accordingly, the use of
acacia intravenously can not be regarded without the possibili-
ties of causing injury, or at least effects that are not necessarily
beneficial.
The results reported in this paper are in line with those on
bronchial musculature described in previous papers, and prove
conclusively that the disturbances produced by the intravenous
injection of these an certain other agents such as arsphenamine,
bear no relationship whatsoever to anaphylaxis or anaphylactic
shock.

CONCLUSIONS

1. The direct application of agar sol and agar so! gel to sur-
viving intestine and uterus produces either no effect or slight
depression of peristalsis.
2. The following agents in high and low concentrations uni-
formly depressed the peristalsis of surviving intestine and
uterus; acacia, dextnin, glycogen, gelatin, starch, human and
horse serums and nuclein solution. Althea extract was some-
what variable, although depression was most common, ii’re-
spective of the chemical reaction.
3. The following agents used as controls produced moderate to
marked stimulation of intestinal and uterine peristalsis: peptone,
and rabbit’s serum. Beef serum was irregular. Definite and
rather marked stimulation was produced by congo red in low
concentrations. This does not agree with the results obtained
on the bronchi of perfused lungs.
4. These effects on intestinal and uterine musculature agree
with those on bronchial musculature (except Congo red) pre-
viously reported.
478 PAUL 3. HANZLIK

5. The results of this study sustain the contention elaborated

in previous papers as to bronchial musculature, that the dis-
turbances produced by the intravenous injection of agar and
various non-protein colloids, and also arsphenamine, bear no
relationship whatsoever to anaphylaxis or anaphylactic shock.

REFERENCES

(1) Hzux AND KARSNER: J. Pharm. Exp. Therap. 1920, xiv, 379, 425.
(2) HANZLIK AND KARSNER: J. Pharm. Exp. Therap., 1920, xiv, 379, 425.
(3) HANzMK AND KARSNER: J. Pharm. Exp. Therap., 1920, xiv, 449..
(4) Knusz: Am. J. Physiol., 1919, xlix, 137 (Proc.).