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. 1999 May;44(5):603–607. doi: 10.1136/gut.44.5.603

Cholinergic blockade inhibits gastro-oesophageal reflux and transient lower oesophageal sphincter relaxation through a central mechanism

J Fang 1, I Sarosiek 1, Y Yamamoto 1, J Liu 1, R Mittal 1
PMCID: PMC1727499  PMID: 10205193

Abstract

BACKGROUND—Atropine, an anticholinergic agent with central and peripheral actions, reduces gastro-oesophageal reflux (GOR) in normal subjects and patients with gastro-oesophageal reflux disease (GORD) by inhibiting the frequency of transient lower oesophageal sphincter relaxation (TLOSR). 
AIMS—To compare the effect of methscopolamine bromide (MSB), a peripherally acting anticholinergic agent, with atropine on the rate and mechanism of GOR in patients with GORD. 
METHODS—Oesophageal motility and pH were recorded for 120 minutes in 10 patients with GORD who were studied on three separate occasions. For the first two recording periods, either atropine (15 µg/kg bolus, 4 µg/kg/h infusion) or saline were infused intravenously. MSB (5 mg orally, four times daily) was given for three days prior to the third recording period. 
RESULTS—Atropine significantly reduced basal LOS pressure (12.6 (0.17) mm Hg to 7.9 (0.17) mm Hg), and the number of TLOSR (8.1 (0.56) to 2.8 (0.55)) and reflux episodes (7.0 (0.63) to 2.0 (0.43)) (p<0.005 for all comparisons). MSB reduced basal LOS pressure (12.6 (0.17) to 8.7 (0.15) mm Hg, p<0.005), but had no effect on the frequency of TLOSR (8.1 (0.56) to 7.5 (0.59)) and reflux episodes (7.0 (0.63) to 4.9 (0.60)) (p>0.05). 
CONCLUSION—In contrast to atropine, MSB has no effect on the rate of TLOSR or GOR in patients with GORD. Atropine induced inhibition of TLOSR and GOR is most likely mediated through a central cholinergic blockade. 



Keywords: gastro-oesophageal reflux; cholinergic blockade; transient lower oesophageal sphincter relaxation

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Figure 1 .

Figure 1

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Study design. (A) Baseline recording; (B) recording following atropine infusion; (C) recording following three days of methscopolamine bromide (MSB). 


Figure 2 .

Figure 2

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Mechanisms of GOR. TLOSR was defined as a sudden drop in LOS pressure of greater than 5 mm Hg in the absence of a pharyngeal contraction and primary oesophageal peristalsis (top left hand panel). Reflux due to deep inspiration was said to occur if there was a drop in oesophageal pH associated with a negative intrathoracic and a positive intragastric pressure (top right hand panel). Reflux due to a swallow occurred when a pharyngeal contraction resulted in a normally conducted oesophageal pressure wave and a brief LOS relaxation associated with a drop in intra-oesophageal pH (bottom left hand panel). Reflux due to an unknown mechanism was when there were no changes in the intra-oesophageal, LOS, and intragastric pressures at the time of reflux (bottom right hand panel). 


Figure 3 .

Figure 3

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Effect of atropine and MSB on basal LOS pressure. Data are grouped in 5 mm Hg pressure intervals and expressed as percentage of total time. *p<0.05 versus saline. 


Figure 4 .

Figure 4

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Effects of atropine and MSB on the mean number of reflux episodes and TLOSRs during the two hour recording period. *p<0.05. 


Figure 5 .

Figure 5

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Mechanism of reflux during saline, atropine, and MSB periods. 


Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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