Baclofen blocks LES relaxation and crural diaphragm inhibition by esophageal and gastric distension in cats

Abstract

Recent studies indicate that baclofen decreases the frequency of TLESR; however, its effect on the crural diaphragm is not known. We evaluated the effects of baclofen on LES relaxation and crural diaphragm inhibition induced by gastric distension and esophageal distension in cats. Five adult cats underwent surgical implantation of wire electrodes into the crural and costal diaphragm for measurement of their EMG activity, respectively. One week after the surgery, animals were lightly sedated and recordings were performed using a manometry catheter equipped with a 2.5-cm balloon. The effects of baclofen (10 mol/kg iv) on the graded esophageal distension and gastric distension-induced LES and crural diaphragm responses were studied. Distension of the esophagus and stomach induces relaxation of the LES and inhibition of the crural diaphragm, simultaneously. Baclofen blocks both the esophageal and the gastric distension-induced relaxation of the LES and inhibition of the crural diaphragm. The magnitude of response to baclofen was significantly larger for the crural diaphragm inhibition than for the LES relaxation. Baclofen, a GABAB receptor agonist, blocks the reflex inhibitory pathway to the LES and crural diaphragm. The reflex inhibitory pathway to the crural diaphragm is more sensitive to blockade by baclofen than the reflex LES inhibitory pathway. transient lower esophageal sphincter relaxation; gastroesophageal reflux; crural diaphragm; GABAB agonist TRANSIENT LOWER ESOPHAGEAL sphincter (LES) relaxation (TLESR) is the major mechanism of gastroesophageal reflux in normal subjects and patients with reflux disease (8, 23). Recent studies in animals and humans reveal that baclofen, a GABA B agonist, inhibits TLESR (3,11,13,28). Studies (10) documenting the blockade of TLESR by baclofen used the LES relaxation criteria to identify TLESR. During TLESR, along with LES, there is also inhibition of the other major component of the antireflux barrier, i.e., the crural diaphragm (21). Distension of the stomach in dogs induces TLESR, which is also associated with inhibition of the crural diaphragm (17). Simultaneous relaxation of the LES and inhibition of crural diaphragm also occurs during distension of the esophagus in cats (1). The effect of baclofen on the crural diaphragm inhibition during TLESR and esophageal distension is not known. The goals of our study were twofold: 1) to determine the effects of baclofen on the gastric distension-mediated LES relaxation and crural diaphragm inhibition, the two important components of the TLESR, and 2) to determine the effects of baclofen on the esophageal distension-mediated relaxation of the LES and inhibition of the crural diaphragm. MATERIALS AND METHODS Diaphragm electrodes implantation.These studies were conducted in five female adult cats, weighing between 3 and 3.7 kg. The protocol for the study was approved by The Animal Ethics Committee of the University of California, San Diego, and San Diego Veterans Affairs Hospital. Under general anesthesia induced by xylazine (1.5 m...

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