Abstract

Background & Aims: Almost 70% of patients complaining of heartburn have no macroscopic evidence of esophageal mucosal damage, and are termed as having either non-erosive reflux disease (NERD) or functional heartburn (FH). Microscopic esophagitis (ME) is common in patients with NERD, and the succeeding changes of dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. It has been reported that edema and inflammation as well as DIS in the tissue are related to the decreasing electrical impedance. The aim of this study was to validate our newly developed bioelectrical admittance method (BAM) as a measure of admittance (numerically equal to the reciprocal of the impedance) of esophageal wall and investigate the differences in bioelectrical admittance between NERD and FH patients. Methods: The BAM was performed at the distal esophagus during upper endoscopy in consecutive 25 patients with heartburn. In each patient, three specimens were taken from the same lesion where the BAM was performed. The histological alterations and gene expression levels of mediators of inflammation and tight junction proteins such as claudin1, claudin4, ZO-1 and occludin were evaluated, and DIS was also evaluated by an electron microscope. The correlation between bioelectrical admittance and tissue resistance measured by an Ussing chamber was investigated for 5 subjects. All patients were prescribed double doses of proton pump inhibitor (PPI) for 2 weeks, and after that patients were divided into 2 groups: good response to PPI (Group A) and poor response to PPI (Group B). Results: There were17 patients in the Group A and 18 patients in the Group B. Symptom severity of heartburn was not significantly different between the two groups. The histopathological findings showed that the prevalence of ME was significantly higher (p<0.05) in the Group A (65%) than in the Group B (10%). DIS also showed similar rates of prevalence. There were differences in expression levels of tight junction proteins between the two groups. Furthermore, patients in the Group A were characterized by the increase in the mRNA expression level of TNFα. There was a significant negative correlation between bioelectrical admittance and tissue resistance evaluated by an Ussing chamber (p<0.05). Patients in the Group A displayed significant higher bioelectrical admittance than those in the Group B (p<0.05), and a significant association between the severity of lowgrade inflammation and the extent of increased bioelectrical admittance of esophageal wall (r=0.45, p<0.05). Conclusions: The BAM is a new method to evaluate esophageal mucosal integrity during upper endoscopy. The low-grade inflammation on esophageal mucosa and electrical conductivity are good clinical markers for the assessment of the responsiveness to PPI in patients with heartburn.

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