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Abstract
It has been previously documented that aspirin induced gastric injury of healthy male volunteers was greater in the morning than in the evening. We have also reported that fasting gastric acid secretion rates and gastric retention times for solids were lower in the morning hours of the circadian cycle. We hypothesized, therefore, that defensive factors in the human stomach may exhibit circadian rhythmicity with greater vulnerability to noxious agents during the morning hours. It has also been hypothesized that an antisecretory agent, with reported protective effects, such as Ranitidine, would affect gastric defense mechanisms differently at different times in the circadian cycle. Transmural electrical potential difference (PD) and prostacyclin (PGI2) production by mucosal biopsy specimens were chosen as putative indicators of gastric defensive status. Accordingly, morning (1000) and evening (2200) studies were performed on 10 fasting healthy male subjects with and without oral Ranitidine (150 mg) given 3 hr before oro-gastric intubation for the measurement of PD and the removal of mucosal biopsy samples. The results showed the following: (1) placebo mean PD values were 3.8 ± 1.6 mv higher (P = 0.04) in the AM compared to PM studies; (2) Ranitidine, when compared to placebo, significantly elevated the absolute value of gastric PD by 34% (-41.0 ± 1.2 vs -54.9 ± 2.6 mv; P < 0.001); (3) the effects of Ranitidine on PD did not differ between the AM and PM studies; (4) in those subjects who participated in a previous AM and PM aspirin injury study, no correlation between resting PD and aspirin-induced gastric lesion numbers was found, with or without Ranitidine treatment; and (5) PGI2 production by incubated biopsy samples in 5 of the 10 subjects was not significantly different (P > 0.05) in the AM versus PM studies (2.7 ± 0.8 vs 3.1 ± l.0 pg/g/hr). Ranitidine had no significant effect on PM measurements, but caused a significant doubling in AM generation rates of PGI2, (2.7 ± 0.8 vs 5.3 ± 1.6 pg/g/hr; P < 0.05).
In conclusion, there is a small but statistically significant difference between the AM and PM gastric PD values. Only two time points were used in this study and more frequent measurements are needed to identify whether gastric PD has a true circadian rhythm. Ranitidine increases gastric PD at both time points and increases PGI2 production in the morning when ASA induced damage (previous study) is greatest. The significance of these effects in gastric cytoprotection is unclear and requires further study.