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Products of cyclooxygenase-2 depress duodenal function in rats subjected to abdominal surgery
1Department of Neuroscience, Division of Physiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
Aim:
Abdominal surgery evokes powerful biological responses that affect gastrointestinal functions. Here we investigate the role of the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoforms in post-operative duodenal ileus.
Methods:
Proximal duodenum of anesthetized rats was perfused in situ with isotonic or hypotonic (50 mM) NaCl. Mucosal bicarbonate secretion, motility, mucosal permeability and effluent osmolality were determined in the absence and presence of different COX inhibitors.
Results:
The majority of control animals had no or few duodenal contractions and bicarbonate secretion averaged 10.9 +/- 1.4 micromol cm(-1) h(-1). These 'paralytic' controls responded to hypotonic NaCl with a small increase in mucosal permeability. In control animals exhibiting spontaneous duodenal contractions, the bicarbonate secretion was 50% higher and the hypotonicity-induced net increase in mucosal permeability sevenfold higher than in 'paralytic' controls. Treatment with the selective COX-2 inhibitors rofecoxib or parecoxib induced duodenal motility, increased bicarbonate secretion and potentiated the hypotonicity-induced increase in mucosal permeability. COX-2-inhibited animals had a twofold greater capacity to adjust luminal osmolality than 'paralytic' controls. The selective COX-1 inhibitor SC-560 only transiently stimulated motility and bicarbonate secretion and the hypotonicity-induced increase in mucosal permeability was smaller than in COX-2-inhibited animals.
Conclusions:
Abdominal surgery increases the synthesis of prostanoids, particularly via the COX-2 isoform. This compromises the ability of the duodenum to contract and to secrete HCO and to adjust luminal osmolality possibly via altered mucosal permeability. It is proposed that studies of gastrointestinal functions in animals subjected to abdominal surgery should include animals pre-treated with a COX-2 inhibitor.
Insights
Cyclooxygenase-2 (COX-2) inhibition improves post-operative duodenal function by enhancing motility and bicarbonate secretion. This suggests COX-2 plays a key role in post-abdominal surgery ileus.
Area of Science:
- Gastroenterology
- Surgical Physiology
- Pharmacology
Background:
- Abdominal surgery significantly impacts gastrointestinal functions, including duodenal motility and secretion.
- Post-operative ileus is a common complication affecting recovery after abdominal procedures.
- The roles of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in post-operative duodenal dysfunction remain to be fully elucidated.
Purpose of the Study:
- To investigate the specific roles of COX-1 and COX-2 isoforms in the development of post-operative duodenal ileus.
- To determine the effects of selective COX-1 and COX-2 inhibition on duodenal function following surgical stress.
Main Methods:
- In situ perfusion of rat proximal duodenum with isotonic or hypotonic NaCl.
- Measurement of mucosal bicarbonate secretion, motility, mucosal permeability, and effluent osmolality.
- Assessment of these parameters in the absence and presence of selective COX-1 and COX-2 inhibitors (SC-560, rofecoxib, parecoxib).
Main Results:
- Selective COX-2 inhibition (rofecoxib, parecoxib) significantly increased duodenal motility, bicarbonate secretion, and mucosal permeability response to hypotonicity.
- COX-2 inhibition enhanced the duodenum's capacity to adjust luminal osmolality.
- Selective COX-1 inhibition (SC-560) showed only transient effects on motility and secretion, with a less pronounced impact on mucosal permeability compared to COX-2 inhibition.
Conclusions:
- Abdominal surgery elevates prostanoid synthesis, primarily via COX-2, impairing duodenal contractility, bicarbonate secretion, and osmolality regulation.
- COX-2 inhibition ameliorates post-operative duodenal ileus by restoring these functions.
- Pre-treatment with COX-2 inhibitors should be considered in studies of gastrointestinal function following abdominal surgery.
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