Volume 116, Issue 3, Pages 573-585 (March 1999) Modulation of gastric sensory and motor functions by nitrergic and α2-adrenergic agents in humans  Miriam Thumshirn, Michael Camilleri, Myung-Gyu Choi, Alan R. Zinsmeister  Gastroenterology  Volume 116, Issue 3, Pages 573-585 (March 1999) DOI: 10.1016/S0016-5085(99)70179-4 Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 1 Experimental design for measurement of gastric compliance, tone, and sensation using a barostatically controlled polyethylene bag in the proximal stomach. 2, Conditioning distention; ▨, sensation; ■, compliance. Gastroenterology 1999 116, 573-585DOI: (10.1016/S0016-5085(99)70179-4) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 2 Representative tracings showing the relaxatory effect of clonidine and nitroglycerin on proximal gastric tone compared with placebo in the fasting period and the preserved accommodation response after meal ingestion. The transient reduction in volume during and immediately after meal ingestion is likely caused by mass effect of the meal, compressing the bag clamped at low pressure. Gastroenterology 1999 116, 573-585DOI: (10.1016/S0016-5085(99)70179-4) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 3 Effects of placebo, clonidine, and nitroglycerin (NTG) on fasting and postprandial tone estimated by the baseline volume within the barostatically controlled polyethylene bag. Clonidine and nitroglycerin increase volumes in the fasting period (*P < 0.03 vs. predrug). The meal induced a significant relaxation of the proximal stomach (#P < 0.03 vs. fasting postdrug period), despite the relaxatory effect of both drugs in the preceding fasting period. 2, Predrug fasting; ▨, postdrug fasting; ■, postdrug, postmeal. Gastroenterology 1999 116, 573-585DOI: (10.1016/S0016-5085(99)70179-4) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 4 Dose-response studies of the effects of clonidine and nitroglycerin on (A and B) fasting and (C and D) postprandial gastric tone. Gastric volume is expressed as natural log on the y-axis. Note the lack of a significant gastric relaxation with 0.1 mg clonidine. Gastroenterology 1999 116, 573-585DOI: (10.1016/S0016-5085(99)70179-4) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 5 Summary of the relationships between aggregate perception score and gastric wall tension at each of the four distention levels (i.e., at 6, 10, 14, and 18 mm Hg above baseline operating pressure). Note that there is a significant relationship (r = 0.4; P < 0.05), but in this pharmacological study, tension accounts for only about 20% of the variance in perception scores. This and the wide range of scores at each tension level suggest that factors other than wall tension also influence perception during distentions. Gastroenterology 1999 116, 573-585DOI: (10.1016/S0016-5085(99)70179-4) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 6 Dose-response summary of the effects of (A) clonidine and (B) nitroglycerin on aggregate perception score (above) and pain score (below) at three levels of gastric wall tension. The data plotted reflect the observed mean scores at the four isobaric distention levels and the mean predicted scores from the repeated measures analysis of covariance incorporating predrug sensation scores (●). Note that clonidine reduces pain sensation, especially in the absence of nitroglycerin. Gastroenterology 1999 116, 573-585DOI: (10.1016/S0016-5085(99)70179-4) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 6 Dose-response summary of the effects of (A) clonidine and (B) nitroglycerin on aggregate perception score (above) and pain score (below) at three levels of gastric wall tension. The data plotted reflect the observed mean scores at the four isobaric distention levels and the mean predicted scores from the repeated measures analysis of covariance incorporating predrug sensation scores (●). Note that clonidine reduces pain sensation, especially in the absence of nitroglycerin. Gastroenterology 1999 116, 573-585DOI: (10.1016/S0016-5085(99)70179-4) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 7 Summary of the dose-related effects of (A) nitroglycerin and (B) clonidine on gastric fasting and postprandial tone and pain score. Data plotted are means ± SEM. Note that 0.1 mg clonidine reduces pain score without affecting gastric volumes fasting or postprandially. In contrast, nitroglycerin relaxes the stomach but does not alter pain scores. Gastroenterology 1999 116, 573-585DOI: (10.1016/S0016-5085(99)70179-4) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 8 13C-Octanoic acid breath test for measurement of gastric emptying of solids after administration of three different doses of clonidine and placebo. Half gastric emptying time (t½) and lag phase (tlag) were similar for placebo and each of the three doses of clonidine. The horizontal lines indicate the 10th and 90th percentile of breath test data from 30 healthy subjects studied previously in our laboratory.42 Gastroenterology 1999 116, 573-585DOI: (10.1016/S0016-5085(99)70179-4) Copyright © 1999 American Gastroenterological Association Terms and Conditions