Temperature dependency of bidirectional flux in the rat intestine subjected to graded ischemia.

Abstract

This study examined the effect of temperature and ischemia on permeation of fluorescently-labeled dextran (M.W. = 4 kDa; FD4) across rat intestinal mucosa. Permeability was evaluated ex vivo using an everted gut sac technique in both the mucosal-to-serosal (M-->S) and serosal-to-mucosal (S-->M) directions. At baseline (B), 30-min of ischemia (I-30) and 60-min of ischemia (I-60), intestinal segments were prepared and incubated at 37 degrees C, 15 degrees C and 4 degrees C for 30 min. Clearance (nl/min/cm2) was calculated based on the accumulated amount of FD4 at 30 min. Both M-->S and S-->M fluxes increased with increasing temperature at B, I-30 and I-60. Ischemic gut (I-30 and I-60) had about a three-fold higher (M-->S)/(S-->M) flux ratio than that of normal gut (p < 0.001). At 4 degrees C, neither M-->S nor S-->M flux was different between B and I-30, but both M-->S and S-->M fluxes significantly increased at I-60, suggesting an increase in permeation via a passive mechanism. Increased bidirectional fluxes at 37 degrees C were obtained in the I-30 and I-60 gut sacs when compared to B. We conclude that FD4 is actively transported across the intestinal mucosa in the S-->M direction and that ischemic injury increases passive diffusion of the probe across the gut wall.