caused death after several hours (at night), the rabbit weighing 2,423
grams.
In certain cases this production of acute symptoms was not entirely a
question of salt action, as was shown by certain other experiments. In
other cases salt action seems to be the important factor, so that the
production of these acute symptoms can not always be considered
characteristic.
* * * * *
FOOTNOTES:
[154] In all cases in which the plants were preserved with
chloroform sealed vessels were used for shipping. The
chloroform was carefully evaporated off in vacuo before
feeding the extract, the evaporation requiring several hours.
The plants were collected by Dr. C. Dwight Marsh, in charge
of the field investigations at Hugo, Colo.
[155] All extracts from dried material were made at
Washington.
=CHRONIC CASES.=
_Experiment No. 6._--February 19, 1906, a large gray rabbit weighing
2,055.3 grams was fed with 60 c.c. of fluid representing the
concentrated aqueous extract of 250 grams of the fresh _Astragalus
mollissimus_, collected September 18, 1905, and preserved in chloroform.
This rabbit was very hard to hold. The ears rested on the body. The
temperature at the time of feeding, 1.30 p.m., was 102.3°F. At 2.57 p.
m. the animal looked dull but resisted handling. At 3.30 p.m. it
urinated. At 4.15 p.m. the temperature was 98.5°F., the pupils were
about the same size as before feeding, and the animal became much
duller. The next day at 12.50 p.m. the temperature was 102.4°F., and
at this time the animal could be handled with greater ease. The animal
ate in the morning. The same amount of extract was again fed at 1.24 p.
m. At 1.35 p.m. the animal was much duller and could be turned on his
back with ease. If disturbed he ran against the wall as if utterly
unconscious of the obstruction. The animal had soft, liquid, brown
stools and tried to lie down as much as possible. If turned on its back
with the feet up it would stay so almost indefinitely. Temperature,
103.8°F.; respiration very rapid. At 2.40 p.m. the temperature was
99.8°F., and the animal died a few minutes later. After death the
pupils were much contracted. The vessels of the dura covering the brain
were much dilated, but the vessels inside the brain were not dilated.
The stomach walls were congested and marked with numerous petechiæ and
covered with mucus.
_Experiment No. 7._--On February 19, 1906, a white and brown rabbit
whose temperature was 103.2°F. was fed 30 c.c. of aqueous fluid
representing the concentrated extract of 125 grams of the fresh
_Astragalus mollissimus_, collected September, 1905, and preserved with
chloroform. The rabbit weighed 1,502.5 grams. This extract was fed at
1.45 p.m., and at 4.15 p.m. the temperature was 102.6°F., but there
were no marked symptoms. The following day at 2.04 p.m. the temperature
registered 102.5°F. The same amount of extract was given at 2.09 p.m.
The temperature at 4 p.m. was 99.8°F., the animal was dull, and the
pupils were perhaps a little smaller. The animal could not be turned
over without resistance. The following day, February 21, at 1.30 p.m.
the temperature was 102.6°F., and at 1.45 the same amount of extract
was given. At 1.54 p.m. the animal was much duller and the breathing
was very rapid. At 4.10 p.m. the temperature was 101.3°F. The animal
had been dull ever since the feeding was begun. It nibbled food shortly
before the last feeding. On February 23 the same amount of extract was
given at 2.16 p.m., temperature 99°F. The breathing was very rapid,
the ears shaking, and there was a sleepy, dull look about the animal. At
3.30 p.m. the animal was dull, but would still walk about if disturbed.
At this time the animal weighed 1,445.8 grams. At 4.30 p.m. the
temperature was 102°F. and the pupils were about normal size. There was
a marked sleepy look about the animal, which sat quietly in its cage.
February 24, at 1 p.m., the animal was very dull and could with ease be
turned on its back with its feet in the air. It would sit in its cage
perfectly quiet. The weight at this time was 1,417.5 grams, the
temperature 96.6°F. On February 26 the animal weighed 1,360.8 grams. It
was dull and refused to eat. The abdomen felt very distended and
tympanitic. February 27 the weight was still 1,360.8 grams, and the
animal sat in its cage as if asleep, with eyes half closed. There was no
diarrhea and the abdomen was very distended. At 11.15 a.m. there was a
general convulsion and the animal fell over. At 12 m. the abdomen seemed
even more swollen, the animal was hardly able to walk, and it fell over,
uttering a cry. Pupils were about normal--perhaps a little smaller. The
animal died at 12.10 p.m.
The post-mortem, made immediately after death, showed the abdomen
markedly tympanitic, and the large intestines could be outlined through
the abdominal walls with ease. The large intestines were of a chocolate
color, intensely congested, and marked with hemorrhages. On opening the
abdomen there was a decided putrefactive odor, and about an ounce of
bloody fluid was found in the peritoneal cavity, together with fibrin
flakes. The stomach was pale, the first three inches of the small
intestine up to where it turned sharply were pale, and below this the
intestines were injected and full of gas and of a dark red color. The
kidneys were 3-1/2 centimeters long and were pale, capsules easily
peeled off; cortex pale. Liver pale and infected with some coccideæ. The
gall bladder was one-quarter inch wide and one inch long. Spleen a
trifle pale; lungs pale, nothing abnormal; heart relaxed. On opening the
stomach gas and fluid, with some food, exuded. The walls were pale, but
pink in some places. There was no marked congestion or hemorrhage or
perforation. The mesenteric vessels were dilated. The upper portion of
the intestines contained a little mucus-like fluid, but lower down
became bloody, and still lower contained pus-like fluid. The walls were
hemorrhagic. The large intestine contained a soft, fecal-like fluid,
very foul. Its walls were much congested and full of hemorrhagic points.
The cortex of the suprarenal bodies was sharply defined, the medullæ
brownish. Brain pale, some dural vessels well marked, no clots or
hemorrhages. Base of brain pale. No congestion seen on cutting into the
brain. Spinal cord showed no hemorrhages or lymph effusions.
_Experiment No. 8._--On February 18, 1906, at 2 p.m., a rabbit whose
temperature was 102.2°F. was fed with the aqueous extract of 125 grams
of fresh _Astragalus mollissimus_, collected in September, 1905, and
preserved in chloroform, 30 c.c. of the fluid being used. At 4.25 p.m.
the temperature was 102.4°F. No symptoms were noted. This rabbit
weighed 1,644.3 grams. On February 20 at 2.09 p.m. the temperature was
102.2°F. and the rabbit showed no symptoms. The same dose was repeated
at 2.15 p.m. At 4 p.m. the temperature was 100.3°F. The rabbit was
dull but could not be turned over without a struggle. February 21 at
1.30 p.m. the temperature was 101.4°F. The same amount of extract was
fed at 1.45 p.m. At this time the animal was dull and breathed more
rapidly. At 4.10 p.m. the temperature was 97.3°F. Next day the same
amount of extract was again given at 2 p.m. At 2.16 p.m. the breathing
became rapid and the animal duller. The ears were directed forward. At
4.15 p.m. the temperature was 101.6°F.; weight 1,757.7 grams; animal
slightly dull. February 24, temperature 102°F., weight 1,786 grams.
March 5, weight 1,729.3 grams. The animal was fed at 3.20 p.m. with a
concentrated extract of 125 grams of _Astragalus mollissimus_, collected
in September. Temperature at time of feeding 100.4°F.; 3.40 p.m., no
symptoms; 4 p.m., temperature 102°F. March 7, weight 1,644.3 grams;
March 8, weight 1,672.6 grams; March 10, weight 1,701 grams; March 12,
weight 1,658.4 grams; March 14, weight 1,701 grams.
In this case, where the same dose was given in a period of five days,
very little effect on the rabbit was noted.
_Experiment No. 9._--On March 1, 1906, a black rabbit weighing 2,664.8
grams was fed with a concentrated aqueous extract of 250 grams of fresh
_Astragalus mollissimus_, collected in the fall of 1905.
On March 5 the weight was 2,296.3 grams. The animal was then given the
same amount of extract. During the afternoon it passed mucus and thick
pieces of feces and was dull; respiration very rapid. March 6, weight
2,282 grams; March 7, 3 p.m., animal very dull and would not eat; sat
hunched up, but resisted being disturbed: weight 2,310.5 grams. March 8,
weight 2,183 grams; March 9, weight 2,069.5 grams. Pupils dilated;
finger could be run almost against the eye, provided the lashes were not
touched, without the animal winking or paying any attention. Rabbit ate
very little and had not urinated since the preceding day. Left ear had
fallen to the side as if the animal were unable to support it. Weight,
1,912.8 grams. From March 9 to March 11, 67 c.c. of cloudy urine were
voided. This did not clear with acetic acid. Left eye tearing. March 10,
head held to right side. March 12, weight 1,786 grams. Left pupil
smaller than right, neither responding to light. Rabbit very weak. March
14, weight 1,729.3 grams. Would not eat. March 16, weight 1,644.3 grams.
Right pupil larger than left, neither responding to light. Diarrhea
present. Breathing noisy. In sitting down she raised herself on her
forelegs, evidently to take the pressure off her abdomen, which was
distended. If disturbed, she would butt against the side of the cage,
apparently oblivious of its presence. Knee jerks were very active,
almost a clonus. Reflex from tendo Achillis active. March 17, forelegs
spread out, head falling to left side. The temperature had fallen below
94°F. and would not register on the ordinary clinical thermometer. The
ears twitched, the head was thrown back, the abdomen was distended, and
the rabbit gritted its teeth. Died. Weight, 1,559.2 grams.
Brain and spinal cord pale. Dural vessels plainly seen but not marked.
Intestinal vessels congested. Stomach pale; nothing apparent
macroscopically save a small pin-point ulcer.[156] Heart relaxed.
Post-mortem examination otherwise negative macroscopically.
_Experiment No. 10._--A mouse-colored rabbit weighing 1,927.8 grams was
fed February 18, 1906, at 2.26 p.m., with a concentrated aqueous
extract of 250 grams of fresh _Astragalus mollissimus_ collected in
September, 1905, and preserved in chloroform water. The temperature of
this rabbit was 102.6°F. The fluid given was 40 c.c. At 2.45 p.m. the
rabbit urinated and at 2.57 p.m. was dull and the respiration became
rapid. The animal then aborted and had three young, two of which showed
some movement after birth, but were apparently premature.
On February 23 the temperature of this rabbit was 102.9°F. at 1.40 p.
m. She was then fed with the same amount of the extract as before. At
2.16 p.m. she lay down and became much duller; left ear fallen to side.
At 3.30 p.m. the rabbit was unable to stand. The pupil of the eye
exposed to the light was dilated. The animal died without a struggle.
The stomach contained much bloody mucus. In the dependent portion of the
stomach near the cardiac end were marked petechiæ in the walls, with
bright-red blood in the stomach itself. The heart was relaxed. The
intestines showed nothing abnormal. The dural vessels of the brain were
dilated; there was a clot on the dura over the fourth ventricle. Spinal
cord and kidneys normal, the capsules not adhering. Weight, 1,786 grams
at death.
_Experiment No. 11._--On March 1, 1906, a rabbit weighing 2,126.2 grams
was fed with a concentrated aqueous extract of 250 grams of the fresh
_Aragallus lamberti_ preserved in chloroform water. On March 5 this dose
was repeated, 37.5 c.c. of the fluid being used. March 6 the rabbit
weighed 1,956 grams; March 7, 1,913.6 grams; March 8, 1,828.5 grams;
March 9, 1,701 grams; March 12, 1,672.6 grams; March 14, 1,644.3 grams.
_Experiment No. 12._ January 19, 1906, a concentrated aqueous extract of
500 grams of the fresh _Aragallus lamberti_ preserved with chloroform
water was fed to a rabbit weighing 785 grams. The temperature at 12.10
p.m., the time of feeding, was 101.6°F. The temperature 1 hour and 43
minutes later was 94.6°F., and the animal died shortly after, showing
the same condition as occurred after feeding extracts of _Astragalus
mollissimus_.
* * * * *
FOOTNOTES:
[156] Compare Plönius, W., Beziehungen d. Geschwürs u. d.
Erosionen d. Magens z. d. funktionell. Störungen u. Krankh.
d. Darmes, Arch. f. Verdauungsk., vol. 13, pp. 180, 270,
1907, and Tixier, L., Anémies Exper. Conséc. aux Ulcér. du
Pylore, Comp. Rend. Hebd. Soc. de Biol., vol. 62, p. 1041,
1907.
=PREGNANT ANIMALS.=
_Experiment No. 13._--A large, gray, pregnant rabbit weighing 2,891.6
grams was fed on February 22, 1906, with 42 c.c. of fluid,
corresponding to the aqueous extract of 250 grams of _Astragalus
mollissimus_ collected in September and October, 1905, and preserved
with chloroform. At 4 p.m. the animal was dull, but still resisted
efforts to handle. On February 24 this animal weighed 2,778.2 grams, and
on February 26 it bore a litter of seven young rabbits. One or two of
these showed movements of the limbs, but were apparently immature. This
rabbit on March 10 weighed 2,537.3 grams; March 12, 2,438 grams; March
14, 2,508.9 grams; March 22, 2,494.7 grams.
_Experiment No. 14._--On March 1, 1906, a black rabbit weighing 2,721.6
grams was fed at 12.15 p.m. with a concentrated aqueous extract of 250
grams of the fresh _Astragalus mollissimus_ collected in September,
1905. On March 2 it weighed 2,438 grams; at 2.58 p.m. it still resisted
efforts to turn it on its back; at 3.15 p.m. it could be turned on its
back with ease. March 6 the weight was 2,338.8 grams; March 7 the
animal was very dull, would not eat, pupils dilated, hind legs
paralyzed; died during the night; weight, 2,267.9 grams.
The stomach walls were pale save at the dependent portion near the
cardiac end, where there was a hemorrhagic, ulcerated area about 1-1/2
by 1-1/2 inches. The intestines were full of gas, but not hemorrhagic.
The uterus contained eight immature foeti. The uterine walls were
hemorrhagic. The kidneys weighed 9-1/2 grams; their medullæ were dark
and the straight tubules well defined. The cerebral dural vessels were
congested and the spinal dural vessels were well defined. The bladder
was found contracted. The blood gave no bands for methæmoglobin, but
showed merely those of oxyhæmoglobin on spectroscopic examination.
_Experiment No. 15._--Control experiments made by feeding water were
negative, except when a large quantity (150 c.c.) of water was given to
a rabbit weighing 1,020.5 grams. The animal died in 12 hours with marked
pallor of the tissues (hydræmia), a pathological condition quite
different from that obtained by feeding extracts of the loco plants, and
no such results were secured with the amount of water used in our
feeding experiments, 50 to 70 c.c.
=SUBCUTANEOUS INJECTIONS.=
_Experiment No. 16._--On February 28, 1906, a white rabbit weighing
581.2 grams was injected subcutaneously at 10.35 a.m. with a
concentrated aqueous extract of 83 grams of fresh _Astragalus
mollissimus_ collected in September, 1905, and preserved with
chloroform. The temperature before injection was 102.1°F. At 1.40 p.m.
the animal was dull; at 3.12 p.m. the temperature registered 99.8°F.
The animal died during the night. The post-mortem examination was
negative. Stomach pale; heart relaxed save left ventricle, which seemed
contracted; dural vessels of the brain dilated; kidneys perhaps normal.
No microscopical examination.
_Experiment No. 17._--February 28, 1906, at 10.25 a.m., a guinea pig
weighing 496 grams was injected subcutaneously with a concentrated
aqueous extract of 83 grams of the fresh _Astragalus mollissimus_
preserved in chloroform water. At 1.40 p.m. there was muscular
twitching. The animal was dull and could be easily turned on his back.
The hind legs began to show weakness. At 1.50 p.m. the hind legs were
almost completely paralyzed and the animal could be easily turned on his
back. Muscles of the limbs twitched and semen was expelled. Animal died
at 2.15 p.m.
Post-mortem showed dural vessels of cord and brain full of blood.
Stomach pinker than normal: mesenteric vessels dilated. Heart almost
empty of blood. Kidneys congested.
=SUMMARY OF FEEDING EXPERIMENTS ON RABBITS.=
These experiments indicate that an acute form of poisoning may be
induced by feeding concentrated aqueous extracts of _Astragalus
mollissimus_ and _Aragallus lamberti_ from Hugo, Colo., and Imperial,
Nebr., to rabbits, and that if the extract is given in smaller and
repeated doses a more prolonged or chronic condition may follow.
The rabbits showing the chronic effects of these plants exhibit symptoms
which have a marked parallelism with those reported as occurring in
larger herbivora (horses and cattle) on the range when locoed; that is,
the loss of appetite (Experiment No. 9), the emaciation and loss in
weight (Experiment No. 9), the dullness and stupor, with more or less
anesthesia (Experiment No. 7), the disturbance in the visual function
(Experiment No. 9), and the mental symptoms (Experiment No. 6). The
occasional abortion compares with what has been observed in larger
animals. The dried _Astragalus mollissimus_ and _Aragallus lamberti_
still retained their poisonous properties, as we were able to kill with
aqueous extracts of the dried plants made in the laboratory under the
proper conditions.
=EXPERIMENTS ON SHEEP.=
_Experiment No. 1._--On May 31, 1906, a sheep weighing 32.2 kilos was
fed with a concentrated aqueous extract of 1,000 grams of the fresh
_Astragalus mollissimus_ preserved in chloroform water. The temperature
at 11 o'clock, the time of feeding, was 103.4°F. At 11.45 a.m. this
dose was repeated. At 12 o'clock the temperature was 104.1°F. At 12.45
the animal urinated. At 1.10 p.m. a similar extract of 2,000 grams was
fed. The total liquid used was 1,500 c.c. On June 1 no symptoms were
noted. On June 5 an extract of 3,000 grams of fresh _Aragallus lamberti_
and 3,000 grams of _Astragalus mollissimus_ was fed. After feeding this
the animal could be easily turned over on its back and its ear pricked
with impunity. The animal at this time weighed 30.8 kilos. On June 6, at
11 a.m., the temperature was 104°F. The sheep had numerous soft
stools, and was very dull, and would not eat. On June 7 the temperature
was 103.7°F. and the sheep still refused to eat. On the 8th the
temperature was 103.2°F. at 10.40 a.m., and the stools were still
numerous and soft.
There were then fed 640 c.c., representing the aqueous extract of 4,000
grams of the fresh _Aragallus lamberti_. The animal could be easily
turned on its back. It weighed at this time 28.57 kilos. On June 9, at
10.47 a.m., the temperature was 103.4°F. The sheep still did not eat,
but had no diarrhea. It now weighed 27.9 kilos, and the temperature was
103°F. at 10.45 a.m.
On June 13 the animal began to eat, and 1,700 c.c. of fluid,
representing 5,500 grams of the fresh _Aragallus lamberti_, were fed.
The temperature at 12.30 p.m. was 103°F. On June 14 the temperature
was 103.4°F., the animal weighed 28.3 kilos, and refused food. On June
16 the weight was 28.3 kilos; the temperature at 2 p.m. was 103.5°F.
There was no diarrhea.
On June 19 the aqueous extract of 1,000 grams of the dried _Astragalus
mollissimus_ was fed with 420 c.c. of water. The temperature was 102.6°
F. On June 20 the temperature was 102.9°F. at 10.45 a.m.
On June 21 500 c.c., representing the aqueous extract of 1,000 grams of
the dried _Astragalus mollissimus_, were again fed. The animal now
weighed 26.9 kilos. On June 26 the animal weighed 26 kilos, and its gait
was very uncertain. The temperature was 104.2°F. It was fed 300 c.c.
of fluid, representing the extract of 400 grams of the dried _Astragalus
mollissimus_. On June 29 the animal weighed 26.8 kilos and the
temperature was 102.8°F. It was fed the extract of 1,000 grams of dried
_Astragalus mollissimus_ in 500 c.c. of water. On June 30, at 10.45 a.
m., the temperature was 104.2°F. The animal was very dull and died at
night.
At autopsy the intestines and stomach merely appeared pale. There were
no worms, and the lungs and other organs appeared normal.
_Experiment No. 2._--A lamb weighing 15.4 kilos was fed on July 6, at
1.10 p.m., with 640 c.c. of fluid, representing the extract of 2,000
grams of _Astragalus mollissimus_. At 1.17 p.m. the animal could be
turned on its back, and it regained its feet with difficulty. At 1.24 p.
m. it urinated and had a stool. The lamb died during the night.
The autopsy the following morning showed the heart filled with clots;
lungs normal save for hypostatic congestion. The cerebral and dural
vessels were dilated. About 1-1/2 teaspoonfuls of bloody serum were
found at the base of the brain. There was none in the lateral
ventricles, and no clots. The kidneys exhibited no marked congestion.
There was no fluid found in the peritoneal or the pleural or pericardial
cavities. The first stomach, however, contained small hemorrhagic spots,
and the second was black. There were small hemorrhages in the
intestines.
_Experiment No. 3._--July 13, 1906, a sheep weighing 19.5 kilos was fed
with 640 c.c. of fluid, representing the extract of 2,000 grams of
_Aragallus lamberti_. The temperature at the time of feeding, 1.10 p.
m., was 105.3°F. At 1.49 p.m. the sheep could be easily turned on its
back. At 2.23 p.m. the temperature was 103.6°F. At 3.42 p.m. the
temperature was 103.5°F. At 4.20 p.m. the respiration was fairly
rapid. On July 14, at 11.15 a.m., the temperature was 103.6°F. The
sheep would run about but could easily be turned over. It had not eaten,
but there was diarrhea present. July 15, at 3.30 p.m., the temperature
was 104°F. The animal had eaten. On July 17 the temperature was 104°F.
and the animal weighed 18.8 kilos. On the 27th it weighed 17.2 kilos; on
August 29, 20.8 kilos.
_Experiment No. 4._--A lamb weighing 19 kilos was fed August 21, 1906,
with 740 c.c., representing the aqueous extract of 2,500 grams of the
fresh _Astragalus mollissimus_, shipped to Washington in September,
1905. This animal ate at night, but the following day was dull. When
seen on August 27 there was diarrhea present and the animal was still
dull. On the 28th the animal died, weighing 16.7 kilos. There was no
autopsy on account of decomposition.
_Experiment No. 5._--A lamb weighing 15.6 kilos was fed on September 4,
1906, with an aqueous extract representing 3,500 grams of the dried
_Aragallus lamberti_, 1,000 c.c. of water being used. The temperature
at the time of feeding was 104.3°F. At 2.48 p.m. the animal on rising
to its feet developed a slight tremor of the fore legs and showed marked
disinclination to stand on its feet. The temperature was 104°F. The
animal died at 4.25 p.m. The post-mortem was negative, save for some
reddening of the second stomach.[157]
These feeding experiments in sheep can not be considered quantitative,
because, as is shown later, aqueous extracts of dried plants are often
inactive, yet poisonous principles may be obtained from the plants by
treatment with digestive fluids.
Extracts of dried loco plants vary much in their toxicity; with some the
writer was unable to kill rabbits, even when an extract of 300 grams of
the dried plant was used. It is interesting to note that when the field
station was established at Hugo, Colo., in 1905, almost all the aqueous
extracts of dried specimens sent to Washington would produce the acute
symptoms of poisoning in rabbits, but during the third season of its
existence many of the samples sent from the same area were much less
active, if not inactive.
* * * * *
FOOTNOTES:
[157] There was a slight odor of chloroform noticed on
opening the stomach, so that perhaps the imperfect removal of
the chloroform due to a hurried evaporation of the extract
should be taken into consideration in this case.
=LABORATORY EXPERIMENTS--CHEMICAL.=