Transmucosal Gastric Leak Induced by Proton Pump Inhibitors
Indocyanine green (ICG) is used as a dye marker of the vascular space in gastroenterology, ophthalmology, neurology, and critical care medicine. It is widely regarded to be inert. We report, however, that ICG demonstrates effects on colonic transepithelial electrical parameters which could form a basis for a growing number of deleterious gastrointestinal and other clinical effects. Short-circuit current (I scc), transepithelial conductance (g t), and transepithelial paracellular flux of 14C-d-mannitol were monitored across sheets of rat distal colon. Dye was introduced to mucosal or serosal tissue surfaces at a concentration similar to that used in vivo (10 μg/ml). ICG decreased I scc by over 50% and g t by over 10%. Transepithelial mannitol flux was not altered. Dye was effective only from the serosal surface. Cyclic AMP–induced spiking of I scc was not affected by ICG. Preincubation with amiloride or furosemide did not affect the action of the dye on g t or I scc. ICG at in vivo dosages is clearly capable of inhibiting ion transport across colon epithelial tissue. The serosal site of action indicates activity on a basal–lateral transport system or diffusion into the cell only across the basal–lateral membrane followed by inhibition of a transporter from the intracellular side. ICG should not be considered inert in vivo. Leakage of ICG from the vascular space into the interstitial fluid space will likely result in tissue morbidity.