Clonidine concentration-dependently inhibits intestinal peristalsis in vitro

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Introduction

The α-adrenoceptor agonist clonidine provides a good alternative for sedation in patients in intensive care units (ICUs). Inhibition of intestinal transport, the development of ileus, and subsequently other complications are major side effects of sedatives used in ICU patients. This study examines whether clonidine exerts an inhibitory effect on intestinal peristalsis.

Methods

Ileal segments of adult guinea-pigs were mounted in silanized organ baths that contained oxygenated Tyrode solution (30 ml, 37°C). Prewarmed Tyrode solution was infused into the intestinal lumen, the infusion rate being 0.5 ml min^-1. The fluid passing the gut lumen was directed into a vertical outlet tubing which ended 4 cm (reflecting a pressure of 400 Pa) above the fluid level of the organ bath. This arrangement caused gradual filling of the intestine. When the intraluminal pressure reached a threshold an aborally moving wave of circular muscle contraction, measured as a spike-like increase in intralumal pressure, propelled the intraluminal fluid to leave the system and thus caused emptying of the segment. The pressure threshold for eliciting peristaltic waves (peristaltic pressure threshold - PPT) was used to quantify the effects of drugs on peristaltic activity. Inhibition of peristalsis was reflected by an increase of PPT. After registration of normal peristalsis the segments were exposed to clonidine (1 nM-100 μM), which was administered cumulatively into the bath, i.e., to the serosal surface of 6 intestinal segments from 6 different guinea-pigs either alone, after application of Tyrode solution (vehicle), or of the adrenoceptor antagonist yohimbine (1 μM).

Results

Clonidine concentration-dependently increased the PPT. While Tyrode solution (vehicle) and 0.1–1 nM clonidine were without any effect on the PPT, 10nM-10 μM clonidine caused an increase of PPT and complete abolition of peristalsis occurred after 100 μM clonidine in 4 of 4 segments tested. Pretreatment with yohimbine (1μM) prevented clonidine (0.1–100 nM) from having any inhibitory effect on PPT.

Conclusions

Clonidine concentration-dependently inhibits the ileal peristaltic reflex in vitro through adrenoceptors located in the intestine. It is assumed that clonidine also affects propulsive peristalsis in ICU patients and thus might contribute to other complications such as ileus and multiple organ failure in those patients.