Water Absorption Enhances the Uptake of Mannitol and Decreases Cr-EDTA/Mannitol Permeability Ratios in Cat Small Intestine In Situ

Abstract

Background: Recently, we hypothesized that mannitol absorption in human intestinal permeability tests is a reflection of small intestinal water absorption and is dependent mainly on the efficiency of the countercurrent multiplier in the villi. This may affect the outcome of clinical double-sugar permeability tests. We tested the hypothesis in cats, another species with an efficient countercurrent multiplier. Methods: The lumen-to-tissue transport of [ 14 C]mannitol and [ 51 Cr]EDTA was studied in in situ perfused jejunum of eight anaesthetized cats using four isotonic perfusion solutions with varying sodium and glucose content. The transport of water was monitored, and the absorption rate of the probes was calculated by their disappearance from the perfusate. Results: There was a significant positive correlation between water absorption and [ 14 C]mannitol clearance from the different perfusates ( r = 0.99; P < 0.01), whereas this correlation was absent for [ 51 Cr]EDTA clearance ( r = 0.05; P = 0.95). There was also a significant negative correlation between water absorption and [ 51 Cr]EDTA/[ 14 C]mannitol clearance ratios ( r = 0.98; P < 0.02). Conclusions: The results show a prominent effect of water absorption on mannitol uptake through pores which, also during glucose transport, exclude Cr-EDTA. The difference in water absorption from the solutions used in cat small intestine is dependent on the effectiveness of the countercurrent multiplier; we conclude that the capability of this mechanism influences mannitol absorption in vivo. Qualitatively comparable results were obtained using oral test solutions with varying NaCl and glucose concentrations in human volunteers. We propose that the functioning of the countercurrent multiplier is essential for the interpretation of double-sugar tests in clinical studies.