SECRETIN II. ITS INFLUENCE ON THE NUMBER OF WHITE CORPUSCLES IN THE CIRCULATING BLOOD ARDREY W. DOWNS AND NATHAN B. EDDY From the Physiological Laboratory of McGill University, Montreal, Canada Received for publication December 18, 1917 In a previous report (1) we have shown that the subcutaneous injection of even a small dose of secretin is able to produce a marked increase in the number of erythrocytes in the circulating blood. In the present report we wish to show that such injections are likewise capable of increasing the number of white corpuscles in the blood stream. The secretin which we used was in all cases prepared from the intestine of the dog. The mucous membrane was scraped off with a dull knife from the upper half of the small intestine, triturated with 50 cc. of 0.4 per cent hydrochloric acid and after standing for two hours was boiled actively. The preparation was neutralized while boiling and filtered. To it was then added sufficient glacial acetic acid to make 2 per cent by volume and the acid extract evaporated to dryness. We have found that such a preparation retains its activity for at least six months. We obtained about 10 mgm. of this dried acid extract per cubic centimeter of original solution. In all of the present series of experiments such an acid extract was used, a sufficient quantity of the dried preparation being dissolved in normal saline solution as needed to make a solution of the same strength as the original filtrate. As in our previous experiments rabbits were used exclusively because it has been shown by Lamson (2) that they do not respond to fright, pain, etc., by an increase in the number of erythrocytes in the circulating blood, as do the cat and dog, and we wished to avoid the use of an anaesthetic. Also to exclude the factor of digestion leucocytosis food and water were withheld from the animals during the experiments. The blood was obtained from the ear of the rabbit with as little manipulation as possible. Specimens were taken simultaneously for counting both white and red corpuscles, 0.5 per cent acetic acid being used as the diluting fluid for the former and normal saline solution for the latter. The counts were made in the usual manner with the Thoma-Zeiss apparatus. TABLE 1 Dose: 1 cc. secretin solution per kilogram of body weight * Red corpuscle counts were not made in experiment 1. † Experiment 7 shows a decrease in the white corpuscle count 9.50 a.m. 9.55 a.m. 10.25 a.m. 10.55 a.m. 11.25 a.m. 11.55 a.m. Experiment 5, November 9, 1917 White blood corpuscles 11,600 per cubic millimeter. Red blood corpuscles 6,054,000 per cubic millimeter. 1 cc. secretin solution (representing 10 mgm. of dried extract) per kilogram of body weight given hypodermatically. White blood corpuscles 14,400 per cubic millimeter. Red blood corpuscles 6,496,000 per cubic millimeter. White blood corpuscles 16,600 per cubic millimeter. Red blood corpuscles 7,184,000 per cubic millimeter. White blood corpuscles 14,400 per cubic millimeter. Red blood corpuscles 5,984,000 per cubic millimeter. White blood corpuscles 12,400 per cubic millimeter. Red blood corpuscles 5,216,000 per cubic millimeter. 12.25 p.m. White blood corpuscles 8,800 per cubic millimeter. Red blood corpuscles 5,574,000 per cubic millimeter. We had determined in our previous experiments that 1 cc. of the secretin solution, equivalent to approximately 10 mgm. of the dried extract, per kilogram of body weight was the most efficient dose to produce an increase in the number of erythrocytes per unit volume of blood and that the preparation was effective when injected subcutaneously. Therefore we selected this dose as our starting point and administered it subcutaneously in all cases. Table 1 summarizes the results of ten such experiments, the effect upon both red and white corpuscles being recorded. Following the table is the protocol of a typical experiment of this group. These experiments show conclusively that not only is secretin solution, when injected subcutaneously, able to produce an increase in the number of erythrocytes in the circulating blood but that it is capable of producing an even greater effect on the number of white blood corpuscles. In addition, however, it shows that the duration of the effect on the number of the corpuscles and the time of appearance of the maximum count are very nearly the same in the two cases-duration of effect on the red blood corpuscles 63.33 minutes, on the white corpuscles 78.5 minutes; maximum count of red blood corpuscles per cubic millimeter in 60 minutes, of white blood corpuscles per cubic millimeter in 51 minutes-the effect being produced quicker in the case of the white corpuscles and persisting longer. We next sought to determine if the dose of 1 cc. of secretin solution per kilogram of body weight was the most efficient dose in the case of the white blood corpuscles as it had been shown to be with regard to the erythrocytes. To do this we performed four experiments using in each a dose of cc. of secretin solution per kilogram of body weight and four experiments using in each 2 cc. of secretion solution per kilogram of body weight. The results of these experiments are shown in tables 2 and 3 respectively. An experiment typical of each group is also given in detail. EXPERIMENT TABLE 2 Dose: 0.5 cc. secretin solution per kilogram of body weight 11.05 a.m. 11.15 a.m. Experiment 11, November 20, 1917 White blood corpuscles 16,800 per cubic millimeter. Red blood corpuscles 6,961,000 per cubic millimeter. 0.5 cc. secretin solution (representing 5 mgm. of dried extract) per kilogram of body weight given hypodermatically. 11.45 a.m. White blood corpuscles 20,600 per cubic millimeter. Red blood corpuscles 7,671,000 per cubic millimeter. 12.15 p.m. White blood corpuscles 18,400 per cubic millimeter. Red blood corpuscles 6,624,000 per cubic millimeter. 12.45 p.m. White blood corpuscles 16,000 per cubic millimeter. Red blood corpuscles 6,168,000 per cubic millimeter. 1.15 p.m. White blood corpuscles 14,500 per cubic millimeter. Red blood corpuscles 5,860,000 per cubic millimeter. * Experiment 21 shows a decrease in the white corpuscle count. 11.00 a.m. 11.05 a.m. 11.35 a.m. 12.05 p.m. 12.35 p.m. 1.05 p.m. 3.05 p.m. Experiment 17, November 27, 1917 White blood corpuscles 11,600 per cubic millimeter. Red blood corpuscles 6,576,000 per cubic millimeter. 2 cc. secretin solution (representing 20 mgm. of the dried extract) per kilogram of body weight given hypodermatically. White blood corpuscles 13,000 per cubic millimeter. Red blood corpuscles 7,263,000 per cubic millimeter. White blood corpuscles 12,000 per cubic millimeter. Red blood corpuscles 6,956,000 per cubic millimeter. White blood corpuscles 12,600 per cubic millimeter. Red blood corpuscles 6,118,000 per cubic millimeter. White blood corpuscles 11,500 per cubic millimeter. Red blood corpuscles 6,288,000 per cubic millimeter. White blood corpuscles 8,500 per cubic millimeter. Red blood corpuscles 6,052,000 per cubic millimeter. A dose of 1 cc. of secretin solution per kilogram of body weight produces an average increase of 44.2 per cent in the number of white corpuscles in 51 minutes, while 0.5 cc. of secretin solution per kilogram produces an increase of only 25.42 per cent in 60 minutes and 2 cc. of secretin solution per kilogram an increase of 38.21 per cent in 40 min-. |