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VII. On the Effects produced on the Circulation and Respiration by Gunshot Injuries of the Cerebral Hemispheres." By S. P. KRAMER, M.D., and VICTOR HORSLEY, M.B., F.R.C.S., F.R.S., Professor of Pathology in University College, London. Received February 21, 1894.

(From the Laboratory of the Pathological Department, University College,

London.)

(Abstract.)

In consequence of the fact that the effects produced on the circulation and respiration by a bullet passing through the cerebral hemispheres are but little understood, the authors instituted a series of pathological experiments on etherised dogs, and of physical experiments on various substances.

The results obtained establish, beyond question, that the primary cause of death under these circumstances is not, as is usually supposed, due to failure of the heart, but to arrest of the respiratory movements. Further, the authors have found, in confirmation of this, that death can be prevented by the employment of artificial respiration, except under certain circumstances detailed in the paper.

After describing the changes in the circulation produced, and which consist of (a) slight initial fall of blood pressure, (b) considerable later rise of blood pressure, (c) preservation of the rhythm of the heart, the authors discuss the physical effects of the projectile on the encephalic contents, and they show, as was originally contended by Professor Kocher, that the action of the bullet is essentially a hydrodynamic one, and that it is the lateral pressures which cause mechanical lesion of the respiratory centre.

In this respect the results obtained further support the original observations of Spencer and Horsley, recently confirmed by Hill, viz., that the respiratory centre is the first to be seriously affected by changes in the intra-cranial tension.

Finally the authors point out that, supervening on the primary arrest of respiration, there ensues a gradual rise in the intra-cranial tension due to the hæmorrhage within the skull cavity, and that the phenomena which then follow are the same as those described in the above-mentioned paper.

VIII. "On the Influence of Carbonic Acid and Oxygen upon the Coagulability of the Blood in Vivo." By A. E. WRIGHT, M.D. (Dubl.), Professor of Pathology, Army Medical School, Netley. Communicated by AUGUSTUS D. WALLER, M.D., F.R.S. Received February 8, 1894.

I have, in the course of previous researches on blood coagulation,* had occasion to suggest that the phenomena with which I was dealing might be explained in a very simple manner by assuming that carbonic acid gas exercised a favourable influence on the occurrence of blood coagulation. The present research consists of an examination of the hypothesis in question.

The method of experimentation employed consisted in determining the alterations of blood coagulability which occurred in animals when alterations were effected in the respiratory gases with which they were supplied.

Details of the Method of Experimentation employed.

The animals experimented upon were dogs and rabbits. The animals were in all cases tracheotomised under the influence of ether (rabbits) or of a mixture of ether and chloroform (dogs). In the case of the dogs, the animals were kept under the influence of the chloroform and ether during the whole course of the experiment. In the case of the rabbits, the repeated inhalations of carbonic acid and other gaseous mixtures served to keep up the anesthesia. The tracheotomy tubes were connected up with a T-tube; one limb of the T-tube was fitted with a Speck's intestinal valve (made of rabbit-gut), and allowed of free expiration into the outer air. The other limb of the T-tube was connected up at pleasure with reservoirs (4,000 c.c. capacity) of pure gases or gaseous mixtures standing over water. The water was carefully kept at the same level inside and outside of the reservoirs during the whole course of an experiment. A convenient check upon this was afforded by the regular opening and closing of the intestinal valve.

The blood for the coagulability estimations was obtained from the ear. In the case of the rabbits, the blood was invariably drawn off from the central artery of the ear. Only rabbits with full ear arteries were employed in the experiments.

The blood coagulability determinations were made by the method of capillary coagulation tubes recently† described by me. The method

Journ. of Physiol.,' vol. 12, No. 2; 'Roy. Irish Acad. Proc.,' 3rd Series, vol. 2, No. 2; Roy. Soc. Proc.,' February, 1893.

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'Brit. Med. Journ.,' July 29th, 1893, and February 3rd, 1894.

differs from the method previously described by Vierordt in the following particulars:--1. A series of capillary tubes, of equal calibre, is employed instead of the single capillary tube employed by Vierordt. 2. Coagulation time is determined by blowing down the capillary tubes, one after another, at regularly increasing intervals until a tube is found to have become blocked by clot. In Vierordt's method the occurrence and duration of coagulation is judged of by passing a chemically cleansed white horse-hair down the capillary tube, and observing the deposition of coagulum upon its surface.

In all cases I employed a column of blood of 5 cm. in length, and received it into tubest which had a diameter of approximately 0.25 mm.

The following precautions were observed in order to ensure accuracy of results:-1. The coagulation tubes were washed out before use successively with distilled water, absolute alcohol, and ether. 2. They were then warmed in an incubator to a temperature of 37° C. 3. A fresh drop of blood was employed for filling each tube. 4. The column of blood was aspirated some little distance up the tubes to prevent desiccation occurring at the orifice. 5. In testing for coagulation the blood was blown out on to a piece of white filter paper in order to ensure the detection of the first traces of clot.

The gases which were experimented with were the following:— Atmospheric air, oxygen, hydrogen, carbonic acid, and a mixture of (approximately) 20 per cent. of oxygen with 80 per cent. of carbonic acid. I also examined the effect of clamping the trachea.

Effect of an Increase of Carbonic Acid.

In order to elicit the effect of an increase of carbonic acid upon coagulability, I caused the animals to inspire out of a reservoir containing a mixture of 1 part (approximately) of oxygen with 4 parts of carbonic acid. This mixture of gases presents the obvious advantage of supplying carbonic acid in association with the normal quantum of oxygen. Determinations of blood coagulability were made when the animals were breathing this mixture of gases, and the results were compared with the "coagulation times" which were elicited immediately before when the animals were breathing atmospheric air. Thirty experiments were made. Out of these twentyseven showed a marked increase of coagulability while the animal was breathing the mixture of carbonic acid and oxygen. In two experiments coagulation time was unaltered, and only in one experiment was a slight diminution of coagulability observed.

Archiv für Heilkunde,' 1878.

These tubes were supplied by Mr. A. E. Dean, Jun., 73, Hatton Garden E.C. This increase of coagulability is well shown in the first ten of the protocols appended to this paper.

In the three experiments last mentioned the coagulability of the blood was already at a maximum when the animal was breathing atmospheric air.

It is to be noted that the blood which was drawn off while the animal was breathing the carbonic acid and oxygen was arterial in colour in all the experiments which have been summarised above. The increase of coagulability must therefore be ascribed to the increase of carbonic acid in the blood, and not to any defect of oxygenation.

It has thus been demonstrated that the increase of carbonic acid in the blood does exert a favourable influence on coagulation.* Carbonic acid is therefore in all probability what I assumed it to be, i.e., a vera causa in the determination of intravascular coagulation to particular vascular areas.

Effect of a Diminution of Carbonic Acid.

This question was studied by examining the condition of coagulability in animals when an atmosphere rich in carbonic acid was replaced by (a) ordinary air, or (b) by oxygen.

a. Results of experiments in which an atmosphere of carbonic acid was replaced by ordinary air.―The result of such a replacement of carbonic acid and oxygen by atmospheric air is a decrease of coagulability to the original norm.

b. Results of experiments in which an atmosphere of carbonic acid and oxygen is replaced by an atmosphere of unmixed oxygen.-The substitution of unmixed oxygen for the mixture of carbonic acid and oxygen is invariably followed by a decrease of coagulability. The diminution may be due to a specific effect of an atmosphere of unmixed oxygen. On the other hand it may with much greater probability be referred to the diminution of carbonic acid in the blood, for the rate of respiration is always extraordinarily accelerated (to 160 respirations per minute and upwards) by the inspiration of oxygen. This view is also suggested by the analogy of the experiments in which air is substituted for the carbonic acid mixture. It is further supported by the fact that the diminution of coagulability is apparently proportionate to the amount of carbonic acid which is present in the blood. The diminution is, for instance, well marked

I have found this statement to hold true also in the case of human blood. The inhalation of an atmosphere which is rich in CO, causes an increased coagulability in my own blood. I have obtained a similar increase of coagulability (associated with an arrest of hæmorrhage) in a case of severe bleeding in hæmophilia. I have also obtained an increased coagulability by inhalation of CO, in the case of three members of another hæmophiliac family.-21/2/94.

Journ. of Physiol.,' vol. 12; 'Roy. Irish Acad. Proc.,' 3rd Series, vol. 2, No. 2.
This result is well shown on the protocols of rabbit 161 and dog 2.

when the blood is rich in carbonic acid (e.g., in protocols of rabbits 165, 163 and 135), while there is practically no diminution of coagulability when the blood has been adequately ventilated by respiration in ordinary air (vide second oxygen inhalation in protocol of rabbit 155).

It evidently results from both these series of experiments that the diminution of carbonic acid in the blood which was assumed by me to afford a clue to the diminished coagulability of peptone* and of blood which has circulated through the lungs and heart alone is in reality capable of exercising a well marked retarding influence upon coagulation.

Effect of a Diminution of Oxygen.

It is extremely difficult to determine with precision what effect the withdrawal of oxygen exercises upon the coagulability of the blood. The difficulty consists in the complication of the phenomena which are due to the withdrawal of oxygen by other phenomena which are due to an increase of carbonic acid in the blood. To elucidate the matter, we evidently require methods which allow of at least a partial dissociation of the effects of the two gases. Such methods should aim at (a) a limitation of the amount of carbonic acid produced in the system after the oxygen is withdrawn; (b) the elimination of the carbonic acid which is produced; (c) a minimising of the effect of the carbonic acid increase. These objects can be partially realised by the two following methods :

:

1. Inhalation of an atmosphere of indifferent gas (e.g., hydrogen) while provision is made for free expiration into the external air.

This method provides to some extent for the elimination of the carbonic acid which is produced after the withdrawal of the oxygen. On the other hand, the method does not provide against the accumulation of carbonic acid which must occur during the dyspnoeic standstill of respiration.

2. Substitution of an atmosphere of unmixed carbonic acid for an atmosphere of carbonic acid and oxygen.

This method presents two advantages: (a) it limits the production of carbonic acid in the system, inasmuch as the withdrawal of oxygen, when made under these particular circumstances, no longer evokes any dyspnoeic spasms; (b) it minimises the effect of any increased carbonic acid tension inasmuch as such increase takes place in a blood which is already almost saturated with carbonic acid.

Roy. Irish Acad. Proc.,' 3rd Series, vol. 2, No. 2, 1891; 'Roy. Soc. Proc.,' February, 1893.

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