protocol for sample 18 being probably referable to either an inaccuracy of observation, or to a rise of CO2 tension due to an unrecorded temporary cessation of respiration, such as would be brought about by the administration of a fresh supply of the anaesthetic. With regard to the apparent primary character of the negative phase of coagulability which samples 2 to 5 appear to establish the existence of, I can only state my belief that an unobserved positive phase of coagulability might have been placed upon record if the samples had been collected immediately after the injection of the tissue-fibrinogen. I omitted to collect these samples early enough, because I was at the moment occupied with supervising the injection. The evidence, however, of Groth's (Dissert. Dorpat. 1884) experiments with leucocytes, in which the phenomena are absolutely identical with those that are observed after injections of tissue-fibrinogen, is quite conclusive as to a positive variation universally preceding the occurrence of a negative variation, even though it might be a positive variation of such short duration that it was necessary to have an assistant to draw off the sample of blood during the actual moment that the injection was proceeding. As to the shortness of the duration of this positive phase, I will quote the following extract from Groth's (Dissert. Dorpat., 1884) Paper:-"Ebenso ausnahmlos aber war die Dauer dieser bis zum Aeussersten gesteigerten Gerinnungsenergie des Blutes nur nach Minuten, ja selbst nach Secunden zu bemessen, und es folgte dann ein ebenso plötzlicher Nachlass bis zur vollständigen Gerinnungsunfähigkeit." With regard to the general question of the injection of a pure tissue-fibrinogen solution being succeeded by a negative as well as by a positive phase, the protocol which has just been quoted would be sufficient evidence; but I shall venture to quote another couple of protocols which appear to me to throw some light upon the great, influence which the concentration of the coagulative fluid exercises upon the results obtained from an injection. Dog 109.--Weight circ. 7 kilogrammes. Made a thick suspension of the washed acetic acid precipitate strained it through calico. Injected 5 cc. of this thick suspension into the jugular vein. Death occurs instantaneously, both venæ cave and both sides of the heart being filled up with one solid clot. No clot in the portal V.; blood from the unclotted vascular areas clots normally. Here evidently the tissuefibrinogen was injected in so concentrated a form that the system was unable to cope with it, or to break it down into albumose. Took another portion of the same coagulative fluid, which had been injected into dog 109, and diluted it with four times its volume of water, and proceeded, as in protocol of dog 119 (quoted above), to determine the condition of coagulability by means of samples drawn from the carotid. Dog 110.-Weight circ. 7 kilogrammes. Sample No. 1.-Withdrawn 3.20; firmly clotted, 3.21. minute. Time, 1 Ran in 5 cc. of the diluted congulating fluid into the jugular at 5.21 p.m. Sample No. 2.-Withdrawn 3.22; semi-fluid still at 3.23; solid, could invert at 3.24. Time, 2 minutes. Sample No. 3.-Withdrawn 3.23; at 3.25 still liquid; 3.27 half solid; solid at 3.29. Time, 6 minutes. Sample No. 4.-Withdrawn 3.25 p.m; half solid, 3.29; solid, at 3.31 p.m. Time, 5 minutes. Sample No. 5.-Withdrawn 3.30; half solid 3.35; solid, 3.37 p.m. Time, 7 minutes. Injected another 5 cc. of coagulating fluid at 3.31 p.m. Sample No. 6.-Withdrawn 3.32; half solid, 3.39; solid, 3.42. Time, 9 minutes. Sample No. 7.-Withdrawn 3.34; half solid, 3.42; solid, 3.48. Time, 14 minutes. Sample No. 8.-Withdrawn 3.40; solid, 3.52 p.m. minutes. Time, 12 Injected another 5 cc. of the coagulating solution at 3.41 p.m. Sample No. 9.-Withdrawn 3.43.; solid at 3.52. Time, 9 minutes. 3.47, injected 5 cc. more. 3.50 p.m. injected another 5 cc. Sample No. 10.--Withdrawn at 3.51; half solid at 3.52; solid at 3.56. Time, 5 minutes. Sample No. 11.-Withdrawn at 3.54; solid at 3.56. Time, 2 minutes. Trachea clamped; no intravascular coagulation produced, but blood coagulates very rapidly after leaving the vessels. In the above quoted protocol, as will be seen, the injection of 25 cc. of the diluted coagulating fluid (corresponding to 5 cc. of the undiluted fluid) did not produce a trace of intravascular coagulation; while the same quantity, injected in a much more concentrated form, led to very extensive intravascular coagulation in a dog of almost exactly the same size which had been kept under similar conditions. It will be seen that the intervals between the injections in this case were in contradistinction to those in the case of dog 119 (vide supra); at first so prolonged that the general curve obtained in the first samples (samples 2 to 7) is one in the direction of negative variation, and only turns in the direction of a positive variation (samples 8 to 11) when the intervals between the injections were considerably shortened. Even then, as we have seen, the positive phase had not become sufficiently pronounced to lead to the formation of intravascular coagula, even when the conditions for the formation of these were made as favourable as possible by the clamping of the trachea. (3.) The diminution and disappearance of the positive phase ought to be marked by the disappearance of the tissue-fibrinogen, as such, from the blood. (4.) The blood of the negative phase should acquire the properties of albumose (peptone) blood. Wooldridge has put observations on record, which show that tissuefibrinogen has ceased to be present, as such, in the blood of the negative-phase areas. He found that the centrifugalized plasma obtained from such blood gave no trace of a precipitate upon the addition of acetic acid. With regard to the agreement in reactions which obtains between albumose (peptone) plasma and the plasma derived from the negative-phase areas after tissue-fibrinogen injections the following observations are, I believe, conclusive: (a) both these plasmas clot upon the addition of tissue-fibrinogen; (b) both plasmas clot (except in very exceptional cases) on passing a stream of CO, through them; (e) both plasmas clot on dilution; and, except in rare instances, (d) upon the addition of a few drops of a 1 per cent. solution of CaCl2; (e) further, both plasmas have a tendency to undergo spontaneous coagulation after a lapse of, say, 12 to 24 hours. (5.) Albumose if set free in the system in considerable quantities would naturally find its way into the urine. We have already seen (vida supra, protocol of dog 1191) that this is what actually takes place. The conditions necessary for the discovery of albumose in the urine, under such circumstances, are evidently (1) that the dog should survive the injection of tissuefibrinogen for some little time, and (2) that the blood-pressure should not have become lowered to such an extent, that no secretion of urine 1 The biuret reaction there observed cannot have been due to the presence of tissue-fibrinogen, because the reaction of the urine was distinctly acid. takes place. Wooldridge had already placed on record the great sinking of blood-pressure that takes place after injections of tissuefibrinogen; and he had recognized it as being something similar to what takes place after injections of "peptone." (6.) The distribution of the areas of positive and negative variation after injections of tissue-fibrinogen ought to have its counterpart in conditions of coagulability of the blood in the various vascular areas after injections of albumose, and an increase of coagulability ought to be observable in "peptone" blood as a consequence of a rise of the CO2 tension in the vessels. We may take the first clause of this proposition by itself, and may quote the following protocol (which is only one of two similar ones) as evidence that the facts actually are as they are assumed under the hypothesis to be: Dog 12.-Weight circ. 3.5 kilogrammes. Experiment begun 5.5 p.m., 20th August, 1891. Ran in 18 cc. of a 10 per cent. solution of Grübler's peptone into the jugular. The characteristic deep and rapid respirations are observed. Two minutes after released clamp on carotid, and collected Sample No. 1-Withdrawn, 5.10 p.m.; loosely clotted at 5.25; nearly solid at 5.30 p.m. Time, 20 minutes. Sample No. 2.-Withdrawn 5.12; not clotted at 5.35. more than 23 minutes. Time, Sample No. 3.-Withdrawn 5.13; not clotted at 5.35. more than 23 minutes. Time, Opened the abdomen, and isolated the portal vein, and pricked a small hole in its wall with a needle. In this manner collected— Sample No. 4-as the blood poured out. This was at 5.17. Can invert this tube at 5.18. Time, 1 minute. Sample No. 5.-Withdrawn from the carotid at 5.20; quite liquid at 5.35 p.m. when observations were broken off. Sample No. 6.-Collected from Vena Porta. As a precaution against obtaining blood which had stagnated in the vein since applying the clip at 5.17, a certain quantity of blood was allowed to flow away from the vein before this sample was collected. Time of collection of sample, 5.22; can evert the tube at 5.24. Time, 2 minutes. Sample No. 7.-Withdrawn from the carotid at 5.23; still liquid at 5.35. 1 See note B at end of Paper. Sample No. 8.-Withdrawn from the Vena Porta at 5.24, the blood having been escaping from the vein ever since the last portion was withdrawn, the clip having been imperfectly adjusted, and the opening in the vein having been previously enlarged. Clots loosely at 5.30. Time, 6 minutes. Sample No. 9.-This sample consisted of all the rest of the blood in the body which was drawn off through the carotid. It was still liquid when the experiment had to be broken off at 5.35, and was loosely clotted by the next morning. Before breaking off the experiment, the solid cylinders of clot which had formed in the test tubes, which had received the portal blood, were shaken out; none of the other tubes could be inverted without spilling their contents. We have thus evidence that the blood in the portal tracts retains its coagulability when the arterial blood has been rendered, to a great extent, incoagulable by an injection of albumose. We have further to adduce evidence that arterial peptone blood can be made to regain coagulability by increasing the tension of CO2 in the vessels. I have made some five experiments in this direction, and in all of them evidence of an increase of coagulability was obtained. I will quote the protocol of one of these experiments. Dog 118.-Weight circ. 6 kilogrammes. Drew off from carotid 85 cc. of blood for a purpose foreign to the present experiment. Then ran in 20 cc. of a 10 per cent. peptone (Grübler's) solution the animal at the same time receiving a fresh supply of chloroform which gave rise to a temporary cessation of respiration. This was at 4.39 p.m. Sample No. 1.-Withdrawn from the carotid at 4.391; clots solid almost immediately. Breathing improves. Withdrew specimens of blood at 4.40, 4.40, and 4.41 p.m. Labelled these Nos. 2, 3, 4. Again withdrew Samples 5, 6, 7, between 4.42 and 4.45 p.m. At 4.45 put a clamp upon the trachea. Sample 8.-Withdrawn at 4.451. Sample 9.-Withdrawn at 4.46; is very venous in colour. Sample 10.-Withdrawn at 4.47; is very venous in colour. Removed clamp from the trachea; breathing has apparently entirely ceased, but is speedily revived by artificial respiration (kneading the chest). Samples 11 and 12.-Drawn off between 4.48 and 4.49. |