Dose-Response Relationship of Graded Doses of Intravenous Histamine Infusion on Gastric Acid Secretion in Man

Abstract

Dose-response curves for the effect of continuous intravenous infusion of histamine on the gastric acid secretion was obtained in nine healthy volunteers of Indian origin. Each subject was studied with 5 doses (20, 40, 60, 80, and 100 μg/kg/h) of histamine acid phosphate administered for 3 h, on separate days, in random fashion. The plateau of secretion occurred in the 2nd h of infusion. The analysis of variance revealed that acid output significantly increased with increasing dose of histamine; the increase in acid output was significant at all dose levels except between 80 and 100 μg/kg/h. The analysis of data using dose of histamine independent of body weight gave a poorer fit to the regression line than that obtained with histamine dose on the basis of body weight, suggesting that dose of histamine should be administered on the basis of body weight. The estimate of calculated V_max and the dose of histamine producing a response 50% of V_max or (K_m) by the three different transformations of the Michaelis-Menten equation gave somewhat different values for both these constants. All these were slightly different from direct estimation of V_max and K_m with analysis of curvilinear regression. The linear transformation using the plot of C_s/v versus C_s gave the best results. The double reciprocal plot underestimated both the constants. The value of Km in Indian subjects was almost six times the value in Western subjects, indicating the relative insensitivity of the parietal cells to histamine in our subjects.

Gastric Acid Secretory Responses to Graded Intravenous Doses of Histamine in Hookworm Anemia

“…Thus, though there was a significantly positive correlation between the dose of histamine as calculated according to body weight and the MAO, there was no such correlation between the absolute dose and the acid response. The same disparity was observed in concurrently studied controls (27). Our findings do not support the view of Desai et al (13), who held that the differ ence in acid outputs of Indian and western individuals is an artifact since the dose of histamine is calculated on the basis of the body weight, which is smaller in Indians.…”

“…These patients were compared with 9 healthy male volunteers, who were not suffering from any systemic or gastrointestinal disease and whose hematologic parameters as well as gastric mucosal morphology were normal. The findings of these healthy controls have been reported previ ously (27).…”

“…Follow ing the correlation between PCM and MAO (4), our findings of grossly reduced MAO in patients with anemia could also indicate lowered PCM in these patients. We demonstrated earlier that higher doses of histamine given intravenously enable normal Indian subjects to produce MAO equal to that produced by western subjects (27). However, the PCM in healthy Indians dying of accidents was not different from that in western subjects (28).…”

“…The criteria of Bock et al (2) for morphological changes in the gastric mucosa were followed. The gastric acid secretion was estimated by using the intravenous histamine infusion method as described in a similar study in healthy controls (27). An intramuscular injection of 25 mg mepyramine maleate preceded the initiation of infusion by half an hour.…”

“…It has been observed that the conventional dose of histamine of 40/ug/kg (b.w.) fails to achieve a maximal acid response in normal Indian males (27). There has been no work on the assessment of MAO in patients with iron deficiency anemia.…”