Aim/Background We previously reported that lye (NaOH) injury (Gastroenterology 1991;100:A128) to esophageal epithelium was time and concentration dependent, as shown by electrical and morphologic evaluation. In this investigation we extend these observations by determining the effects of lye using direct measurements of esophageal permeability.
Methods Rabbit esophageal epithelium was mounted in Ussing chambers and the tissues bathed in 10 mM HEPES-buffered solution bubbled with 100% O2. The electrical potential difference (PD), short-circuit current (Isc), and transepithelial resistance (RT) were monitored during stepwise luminal exposure to NaOH at pHs ranging from 7.4-12.0 or to a fixed concentration of NaOH. Before and after exposure, tissue permeability was assessed by adding 4 kD FITC-labeled dextrans to the luminal bath and measuring its flux into the serosal solution at 45 and 90 minutes.
Results Luminal pHs ≤ 11 had no observable effect on electrical or morphologic parameters of the tissue but when luminal pH was increased to 11.5, there was an abrupt increase in esophageal PD and Isc and a decline in RT. When luminal pH was increased to 12, PD and Isc rose briefly and then fell progressively to zero by 40 minutes while RT rapidly declined to zero over the same time frame. 4 kD FITC-dextran fluxes were performed at fixed pHs of 8.6, 11.7, and 12.1 yielding values of 3-, 28-, and 167-fold over those for control pH 7.4 respectively. As with the electrical parameters, the dextran fluxes were observed to be both time and concentration dependent.
Conclusions Lye injury to esophageal epithelium is time and concentration dependent. It is initiated at luminal pHs of 11.5 and manifest by injury to the cellular and paracellular pathways as reflected by electrical, morphological, and functional changes in epithelial permeability. Support: NIH DK36013.