Evaluation of viability of excised rat intestinal segments in the Ussing chamber: investigation of morphology, electrical parameters, and permeability characteristics.
OBJECTIVE
To clarify relations between alterations in electrical and permeability data with time and to elaborate accompanying structural changes of intestinal segments in Ussing chamber experiments.


METHODS
Excised intestinal segments from the rat were studied in a modified Ussing chamber. Experiments were run up to 180 minutes during which the electrical parameters, PD, SCC, and R, were measured and the permeability coefficients (Papp) of mannitol and propranolol were determined. Each segment was observed under the light microscope for morphological evaluation.


RESULTS
PD and SCC values showed a decrease for most segments while the R values remained steady throughout the experiment. The Papp for propranolol increased aborally to the small intestine. For mannitol, the reversed was observed. In some cases, there was a time-dependent change in permeability for these marker molecules. The main morphological changes observed were a decreased nucleo-apical distance, decreased villi amplification factor, initial edema, cell sloughing, and epithelial restitution.


CONCLUSIONS
The time-dependent changes in permeability coefficients of mannitol and propranolol are suggested to be related to changes in electrical parameters and morphological alterations. Presented data illustrates the importance of information regarding time-dependent structural changes for correct interpretation of permeability data.
Polentarutti
B I
BI
Astra Hässle AB, Biopharmaceutics, Pharmaceutical R & D, Mölndal, Sweden.
Peterson
A L
AL
Sjöberg
A K
AK
Anderberg
E K
EK
Utter
L M
LM
Ungell
A L
AL
D000704:Analysis of Variance; D000818:Animals; D002463:Cell Membrane Permeability; D002470:Cell Survival; D004553:Electric Conductivity; D004594:Electrophysiology; D005069:Evaluation Studies as Topic; D066298:In Vitro Techniques; D007422:Intestines / Q000166:cytology* / Q000502:physiology*; D008297:Male; D008353:Mannitol / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D008353:Mannitol