I. Effect of acetylsalicylic acid upon gastric activity and the modifying action of calcium gluconate and sodium bicarbonate

Conclusions

1. In some normal human subjects and normal dogs, single oral doses (1–2 gms.) of acetylsalicylic acid caused gastric retention; the addition of calcium gluconate tended to increase the degree of retention while the addition of sodium bicarbonate increased the rate of gastric evacuation.

2. In normal human subjects and normal dogs, single oral doses of acetylsalicylic acid increased the total titrable acidity of the stomach contents; the addition of calcium gluconate diminished the rise in the acidity, while the addition of sodium bicarbonate decreased the acidity of the contents below that of the controls.

3. In dogs with pouches of the entire stomach, the local application of acetylsalicylic acid caused a definite increase in the neutral chloride, or diluting secretion of the stomach, the addition of calcium gluconate resulted in only a slight increase in the diluting secretion, while the addition of sodium bicarbonate to the acetylsalicylic acid also resulted in only a slight increase in the diluting secretion. None of the solutions increased the formation of HCl significantly.

4. Prolonged daily administration of acetylsalicylic acid to normal dogs to dogs with Pavlov stomach pouches resulted in definite augmentation of gastric secretion. With the addition of calcium gluconate the increase was not nearly so marked, while sodium bicarbonate and acetylsalicylic acid actually caused a decrease in the gastric secretion below the control values.

5. The neutralizing and “inhibiting” actions of sodium bicarbonate and calcium gluconate on the titrable acidity of the gastric contents, and on the output of hydrochloric acid under the conditions of our experiment may play a definite role in the ameliorating effects of these substances upon the degree of gastric irritation and the incidence of ulceration produced by the prolonged oral administration of acetylsalicylic acid to dogs. Whereas the protective action of sodium bicarbonate may be adequately explained by a reduction of acid irritation, this is not true of calcium gluconate, whose protective action against digestive disturbances appears to be due also in part to some systemic action of calcium.

6. From the evidence available it would appear that to obtain optimal protection when giving salicylates in large doses, the salicylates should be administered with sodium bicarbonate and calcium gluconate.