tenmperature of the bath would soon be acquired. This bath was kept at factor in its determination. According to him, the value of any method
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1 THE EFFECT OF TEMPERATURE ON BLOOD COAGULATION TIME. By SUTHERLAND SiMPSON and A. T. RASMUSSEN. (From the Physiological Laboratory, Medical College, Cornell University, Ithaca, N.Y., U.S.A.) (With five figures in the text.) (Received for pablication 22nd February 191.) ADDIS (1) in describing his improved method of measuring the blood coagulation time calls attention to the importance of temperature as a factor in its determination. According to him, the value of any method is mainly determined by its success, or want of success, in maintaining a constant temperature. In view of this fact, the chief difficulty we anticipated in our investigations into the effect on blood coagulation of removing the parathyroids was the rise in body temperature which always accompanies parathyroid tetany if this is at all severe. A priori it might be supposed that a hypernormal temperature of the blood, before it was withdrawn from the artery, would shorten its coagulation time, and that a subnormal temnperature would increase it. To test this we performed a series of experiments in which the temperature of the animal could be raised or lowered at will, while the blood coagulation time was being recorded by the method of Cannon and Mendenhall (2), as already described. Nine dogs were used in this series. The animal was anaesthetised with ether and placed on the Brodie operating table, where a trachea tube was introduced and the saphenous branch of the femoral artery, usually on the left side, prepared. The dog was then partially immersed in a large bath of normal saline, the temperature of which could be raised by a suitable gas burner and if necessary by the addition of hot saline as well, or lowered by the introduction of ice. A small incision was made in the linea alba, and through this opening a thermometer was introduced into the abdominal cavity, the bulb being pushed deep down under the liver. From the stern of this thermometer, which projected free, the body temperature was read; this would be approximately the temperature of the circulating blood. The technique adopted in estimating the blood coagulation time was similar to that described in the preceding communication (3). When the cannula was filled to the proper level with blood it was at once transferred to a water bath at 250 C., the plunger and lever adjusted, and a record made every half minute till the blood clotted. Not more than a few seconds intervened between the filling of the cannula and its transference to the water bath, and by such a small quantity of blood, disposed in a thin column, the tenmperature of the bath would soon be acquired. This bath was kept at a constant teinperature (25C C.) throughout the entire experiment.
2 10 Sutherland Simpson and Rasmussen The method of procedure will be more readily understood from the following protocols, taken at random from the series of nine experiments. Protocol VII. July 2, Experiment VII.-Dog, ; weight 14-7 kilos; age 1 year a.m. Dog transferred to ether box ,, Dog placed on operating table ,, Tracheal tube and abdominal thermometer introduced ,, Began operation to expose and prepare artery ,, Abdominal temperature C ,, Artery incised ,, Dog partially immersed in bath at 40 C. Time. Observa- tion. Boytm.Respira- Pulse. Coag. D Bdy temp. tions. time a.m i min ,, ,, 11.48,, 3 42, ,, 11.5,, ,, 12.04,, 5 42, ,, 12.11,, 41-4,, 12.21,, 7 40, ,, 12.28,, ,, 10 37,0,, ,, ,, 13 33, ,, 1.2,, 14 32, ,, 15 31, ,, 1.44,, ,, 1.54,, ,, 2.03,, ,, 2.25,, , 2.4,, ,, 2.5,, ,, " ,, 24 25,0 5,, 3.4,, ,, , 4.07,, ,, 4.17,, ,, 4.27, ,, 4.38,, ,, 4.47,, ,, ,, 5.08,, 33 3, , 5.15,, & ,, ,, 5.43,, ,, 5.51,, ,, , ,,.05,, ,, ,, ,,.40,, Stopped br eathing and did not rec over
3 Effect of Temperature on Blood Coagulation Time The first column gives the time when the clamp was released to fill the cannula, the second column tlhe number of the observation, the third the temperature of the abdominal cavity in degrees centigrade, the fourth and fifth the respiratory and pulse rates respectively per minute, and the last column the coagulation time in miinutes. Protocol VIII. July 3, Experiment VIII.-Dog, $; weight 13 2 kilos; age 13 months a.m. Dog put into ether box ,, Dog placed on table ,, Tracheal tube and abdominal thermometer introduced ,, Began operation to prepare artery. Abdomi. temp. 390 C ,, Artery incised ,, t Placed in saline bath at temp. of 4 C. Abdom. temp. 390 C. Time a.m ,, ,, " ,, 11.48,, noon p.m ', ,, , ,, ,, 1 1.4,, ,, , ,, ,, " ,, ,, , , ,, ,, ,, ,, , ,, ,, ,. 37 Body temp. Body temp. Observation. Respira- Respirationis. 40,5 8 42' , * ,3 27' " ' ; Dog died at this stage of hyperpyrexia. VOL. X., NO Pulse Coag. time. 4 min. 3 4 i , i 4 1 2,, ,, 7,, 1 44,,, 12, 11 11
4 12 Suthlerlancd Simpson anid RasIm ussen -~-~ _. 0,,o._0 C). -t e
5 Effect of Temperature on Blood Coagulation Time Figs. 1 and 2 show the graphic records obtained in these two experiments-vii. and VIII. The following table gives the coagulation times at certain selected abdominal temperatures for the whole series. The figures at the top of each column represent the selected temperatures, those below the average coagulation time between the temperature limits, and the Roman numerals, at the left side, the number of the animal. TABLE I Exp _ _29O C. c. c. C. C. C c. c. C. C. 13 II I t.. I III. 8& & IV * V i VI. * i 8 5* VII VIII... 5,5 7,5 5 4 IX It will be evident that although there is no constant relationship between the body temperature and the blood coagulation time, for most of the animals it is slightly shorter when the temperature lies between 340 C. and 410 C. than for temperatures either above or below these limits. The difference is scarcely perceptible, however, and there are several exceptions. Comparing the results of these experiments with those of our other series, taken under normal conditions, before the parathyroid glands were removed (3), we find that the coagulability of the blood does not show the same variation in the successive observations when the body temperature is normal and constant as when it is rising and falling. It has been stated that prolonged etherisation has an effect on the coagulability of the blood, and our next experiment was made to determine this point. The dog was prepared in the usual way with a tube in the trachea, through which ether was administered, and a thermometer in the abdominal cavity, the blood being taken from the left saphenous artery. It was placed in a bath of warm 0 9 per cent. normal saline, so that the body temperature could be kept constant throughout the experiment; the readings of the abdominal thermometer, as a matter of fact, ranged between 390 C. and 400 C. The animal was completely and continuously under the influence of the anesthetic from 10.3 a.m. till 4.5 p.m., that is, six hours, and it will be seen from an examination of the records (fig. 3) that etherisation appears
6 14 Suthwerlanld SiiAp,soii and RasllIIS.1-4'II C). 4 C-) - Cl
7 Effect of Temperature on Blood Coagulation Time neither to increase nor diminish the coagulation time. Dividing the interval between a.m. and 4.5 p.m., during which the observations were being made, into five periods, the average coagulation time for the first period, including 1st to 5th observations, is 5 minutes, for the second period 5-, for the third 5 7, for the fourth 5 5, and for the fifth and last period (3.27 to 4.5 p.n.) 5 2 minutes (see fig. 3). Judging by thbese results, prolonged etherisation does not appear to affect appreciably the coagulation time in the dog. Lastly, we made two experiments to test the effect of altering the temperature of the water bath in which the cannulie were immersed while the blood was undergoing coagulation, the temperature of the animal, and consequently of the blood before it was withdrawn from the vessel, being normal and approximately constant. Here there is a marked contrast, as the following protocol of one of these experiments, taken as a sample, will show. Protocol X. December 14, Dog t; body weight 12 4 kilos; age 1 year a.m. Dog closed in ether chamber. 9.50,, Dog placed on table; trachea tube inserted, R.T C ,, Began operation to expose left femoral artery ,, Saphenous branch incised. Tinte Ọbserva- Temp. of bath. Coag. time. Rectal temp a.m C min C ,, 2 15,, ,, 20,, ,, ,, 5 25,, ,, 25 4*0,, ,, ,, 8 30,, ,, 9 35,, ,, 10 35,, p noon 11 40,, 2_0,, 383,, p.m ,, : ,, 13 40,, ,, 14 45,, ,, ,, 25,, 38A,, 12.33,, 1 45,, ,, ,, 18 50,, ,, 19 50,, ,, 20 55,, 40,, 382,, 1.15., 21 55,, , 22 0),, 17-5,, Still no clot 1,57,, 23 57,, 1 7 0,. 2.20,, 24 5,, 17 0,,,,, 2.41,, Dog transferred to cold batlh aind exreriment continued. Thermometer introduced into ab(lominal cavity as before. 15 ['7able continued on p. 18.
8 1 Sutheiland Siiupsoin and Rasmussen C e~~~._~~~~~ C C-M
9 Effect of Te Temperatii~~~~~~e i4t_;eneb1 Ofl 00 '' to5ua1tion Time 17 o o a, 4 co vc) co 0 a.h 0 -C.en a, '.m CD * a, 0'C4 c < co _ 00 Qco o m A. -C) 4,'0 o0 *S.< o 0, a, e~.0 o V. 0a ~0 ) 4a, -a, 5- C_d P oc o a,e a,0 a, +8>
10 18 Effect' of Temperature on Blood Coagulation Time Time. Observa- Temiip. of abdomen. Coag. time. Rectal temp. tion p.m C. 4,5 min. 4.00,, 2 27-,, ,, ,, ,, Filled bath with saline at 50 C. 4.34,, C. 3-0,, 4.39,, ,5 4.4,, 31-5,, ,, ,, 3.5,, 5.01, ,, 9 371,, 2-5,, 5.12,, 10 37, ,, ,, ,, , 13 40, ,, ,, 5.4,, 15 41, ,, 1 414,, 30, 5.57,, ,, ,, Dog died The records of this experiment are shown in fig. 4. In the next experiment, the second and last of this series, the same general result is obtained. To save space only the beginning and the end of the record is shown in this experiment (fig. 5). With the blood at 100 C. the coagulation time was 19-5 minutes, and at 550 C. it refused to clot. SUMMARY. In the dog variation in the temperature of the blood, before it is withdrawn from the artery, between the limits of 250 C. and C., does not appear to affect its coagulation time provided it is kept at a constant (250 C.) temperature afterwards. Prolonged etherisation does not affect the coagulation time appreciably. Changes in the temperature of the blood, after it is withdrawn from the body, produce a marked affect on its coagulation time. From 100 C. to about 400 C. the time is shortened as the temperature rises, and beyond this from 400 C. upwards, it is lengthened. At 550 C. or 50 C. the blood does not coagulate at all. BIBLIOGRAPHY. (1) ADDIS, T., Quart. Journ. Exper. Physiol., 1908, vol. i. p (2) CANNON and MENDENHALL, Amner. Journ. Physiol, 1914, vol. xxxiv. p (3) SIMPSON and RASMUSSEN, Quart. Journ. Exper. Physiol., 191, vol. x. p. 145.
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