Studies on the regulation of blood coagulation from the pharmacological point of view (Part I) On the mehods of determining both the coagulation time of blood and some coagulative components, and on certain conditions to act upon them

Before the regulation of blood coagulation should be studied pharmacologically, I have, first of all as a means requisite for the desired object, selected out of or improved the existing method of determining both the coagulation time and coagulable components. In the second place, after giving some critical comments on those methods and making carful experiments upon various ploblems that have not yet been solved comprehensively, I have brought to light some conclusive evidences which stand test fairly, as follows: I 1; My own apparatus used for measuring the required time for clotting is but simple. As seen in Fig. 1, two glass-cylinders are put in an oblong kettle, Petres' diches of big size being put in each cylinder. Either cold or hot water or ice-water is filled up in these vessels, in order to keep on a difinite temperature. while the dishes being filled with a piece of gauze well soaked in water. A piece of filter-paper is laid on it, on which a watch-glass is put. The mater to be tested is run dawn on the glass. As for the determination of coagulation time, a hooked glass-thread is used for hooking the matter up at about the middle of it every 15 seconds. The first period of coagulation time lasts until when a tiny piece of fibrin sticks on the end of the glass-thread, and the second period comes to an end as a whole coagulated blood is crear of the face of the watch-glass by means of a glass-rod. This method requires no special skill in practice, and is good for oft-repeated experiments because of a little amount of blood used, and is not only affected by the change of external temperature and humidity, but has also an advantage of pointing out each end of the two periods precisely. 2. While there is an average value of 30 minutes for the coagulation time of a normal rabbit at the temperature ranging from 21°C to 23°C by Fonio's method, my own method takes far less time, an average time for coagulation being 7 minutes at 20°C in the first period, varying from 6.5 to 8 minutes, while taking 15.5 minutes on an average the second period, ranging from 12 minutes to 18.5 minutes. When tried with a single animal, it takes 15 seconds in the first period, and 30 to 45 seconds in the second period respectively, under repeated tests of blood. 3. By my method, as by Fonio's, there is some difference in coagulation time according as the amount of blood used. There exists, however, but little disparity in time in either experiment with a difinite amount used from 0.5 to 2.0 cc by Fonio's method, or with the amount of 2 to 4 gtt. by mine. Any increased amount of blood does not always run parallel to the length of its coagulation time, nor the coagulation is strikingly belated on account of a little amount used. 4. It is an unchangeable fact that the external temperature has no less influence upon the coagulation time. It has been tried by my method at the temperature ranging from 5° to 42°C, marking by drawing a curve line, as do by Bürker's, the result, which shows both the first and second period of coagulation become shorter as the external temperature rises higher. 5. The influence of body temperature upon the coagulation time of blood was inspected by means of heat puncture with a result showing the fact that there is a well-defined parallelism between the curves of the change of body temperature and coagulation time. 6. While it is true that certain amount of carbonic acid in blood plays part in its coagulation time, scholars opinion on the variation of clotting time between the venous and arterial blood has not agreed yet, it has been confirmed the fact that the coagulation time of the former is certainly longer than that of the latter in my own experiments by Fonio's method; but it is not certain whether it is due to only the difference in the tension of carbonic gas. II 1. My methods of measuring fibrinogen, thrombin, anti-thrombin have been much improved based on the principle of Wohlgemuth's methods, are not only good for repeated examinations, but are, also, able to indicate the desired results in a mere fragments of time. 2. Owing to the individuality of animals, the contained amount of those components varies, but when it is repeatedly experimented on the same animal, the result is generally unchangeable. 3. Fibrinogen solution used by myself contains prothrombin. 4. While the potency of serum decreases with the lapse of time, if it is applied to actively, no preeeptible change can be seen in its activity so long as several houres after its being taken out. It is, therefore, best fitted, accompany-ing no great troubles, to use an active serum as thrombin solution in measuring fibrinogen in blood. 5. Serum contains some amount of kinase, yet the amount of calcium in serum is too little for kinase to present itself in its activity, so that the coagulable power of serum on fibrinogen is strengthend when some of calcium is added to the serum in case the power relaxes in both normal condition and wanting in calcium. I doubt kinase will sway a great influence upon my method of measuring thrombin in serum. 6. Hybrid-serum coagulate fibrinogen and transform it into fibrin but the speed of transforming being greatly varied, it may be safely be said the serum has a singular property so far as coagulation time is conserned.

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