It is a constant claim that so many and complex are the factors concerned in physiologic processes, that it is not unusual for clinical deductions to establish themselves in the face of a priori laboratory dicta. We considered it desirable, therefore, to test the action of secretin, orally administered, in the most direct manner, and the one freest from possible criticism. With this in view, we performed a series of experiments on normal unanesthetized dogs having permanent pancreatic fistulas.
Method.—In the operations for permanent pancreatic fistulas we followed closely the technic developed by Pawlow,[89] and with excellent results. The dogs maintain themselves in splendid condition if proper care is taken. This consists in feeding them only with bread and milk, and giving sodium bicarbonate daily. The dogs were given this treatment in the evening so that experimental procedure might be carried on in the day with empty stomach under constant conditions. Freshly prepared secretin in large quantities was given by stomach tube to these dogs, and the response of the pancreas studied and compared with the response obtained from control preparations. The same preparation was generally not given on consecutive days.
TABLE 4.—DETAIL OF TYPICAL EXPERIMENTS
Dogs with pancreatic fistulas, showing that secretin given by mouth has no action on the pancreas
| Material Fed by Stomach Tube | Rate of Secretion of Pancreatic Juice in C.c. per Hr. | |||||
| Continuous Secretion Before Feeding | Continuous Secretion After Feeding | |||||
| First Hour | Second Hour | Third Hour | First Hour | Second Hour | Third Hour | |
150 c.c. active secretin, slightly acid | 6.5 | 3.6 | 3.9 | 20.0 | 6.0 | 8.0 |
150 c.c. active secretin, slightly alkaline | 13.0 | 11.0 | 5.0 | 23.0 | 26.0 | 12.0 |
150 c.c. secretin passed through Berkefeld | 7.8 | 7.5 | 7.4 | 23.0 | 13.0 | 11.0 |
150 c.c. extract of colon | 11.6 | 12.0 | 11.4 | 30.0 | 19.6 | 14.8 |
150 c.c. extract of gastric mucosa | 10.0 | 7.0 | 8.0 | 23.0 | 7.5 | 4.0 |
150 c.c. extract of muscle | 6.9 | 11.0 | 6.4 | 35.0 | 5.0 | 7.0 |
150 c.c. 0.4% HCl (diluted to 250 c.c.) | 6.0 | 8.0 | 4.0 | 33.0 | 36.0 | 17.0 |
Results.—We have data from six dogs with a total of seventy-six experiments. As shown in Table 4, the administration of secretin causes an increase in the flow of pancreatic juice, but the administration of inert substances as extracts of colon, gastric mucosa or muscle causes a like increase. The activity of the secretin may be reduced to a low value by exposure to sunlight, or filtering through a Berkefeld filter, yet the response of the pancreas is not correspondingly reduced. The secretion that occurs in the control cases, every one will admit, is but secondary to the production of gastric juice with its accompanying hydrochloric acid, that is, excited by virtue of the extractives and water in the preparations. Such, we can prove, is the only action of secretin. A mixture of gelatin, peptone and salt water, the chief incidental constituents of a secretin preparation, gives as striking results as ever obtained from secretin administration. Yet the objection may be made that the response of the pancreas that is due to the incidental constituents of secretin is maximal, and that the secretin consequently has no opportunity to display its particular potency. But, as inspection of the accompanying tables illustrate, the administration of hydrochloric acid shows that the response is by no means maximal. Let us cite a striking experiment. For three hours before the administration of hydrochloric acid, the secretion in cubic centimeters was respectively 29.4, 11.75 and 35.4 c.c.; for the three hours after, respectively 88.0, 49.0 and 40.5 c.c.
Fig. 1.—Tracings (reduced two-thirds) showing failure of Secretogen, Elixir Secretogen, and Duodenin to stimulate the flow of pancreatic juice even when administered intravenously in amounts three times greater than that recommended to be given by mouth. Dog: light ether anesthesia; cannula in the pancreatic duct; a, carotid blood pressure; b, flow of pancreatic juice in drops; c, signal showing where the intravenous injections were made. Tracing A: Reading from left to right, the five intravenous injections are: (1) three tablets of Secretogen digested with 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (2) three tablets of Secretogen boiled in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (3) three tablets of Secretogen in 15 c.c. 0.9 per cent. sodium chlorid; (4) three tablets of Secretogen in 15 c.c. of 70 per cent. alcohol; (5) 15 c.c. Elixir Secretogen. Tracing B: reading from left to right, the four intravenous injections are: (1) 5 c.c. secretin made fresh from dog’s duodenal mucosa; (2) three tablets of Duodenin digested in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (3) three tablets of Duodenin boiled in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (4) three tablets of Duodenin in 15 c.c. sodium chlorid (0.9 per cent.).
TABLE 5.—SUMMARY OF EXPERIMENTS
Dogs with pancreatic fistula, weight 14 kg. Secretin given by mouth