An in vitro study with an ussing chamber showing that unfractionated heparin crosses rat gastric mucosa.
Heparin, traditionally given parenterally, is used to treat and prevent thrombosis. Our previous results suggest that orally administered unfractionated heparin (UFH) is absorbed and has antithrombotic effects. However, there is little evidence indicating the site and mechanism of heparin absorption. Our aim was to determine whether the stomach is an absorption site. Rat gastric mucosa was mounted in an Ussing chamber, and UFH was added to the mucosal buffer at pH 7.4. Potential difference (PD), resistance (R), and short circuit current (I(sc)) across the mucosa were determined comparing the mucosal to the serosal side. Mucosal and serosal buffers and tissue were analyzed for chemical heparin and anticoagulant activity, antifactor Xa (anti-Xa) and antifactor IIa (anti-IIa) activity. The PD became more negative on UFH addition. Following a lag period, PD returned to the resting level. Changes in R followed those in PD, whereas I(sc) did not change. Heparin was found in the serosal and mucosal buffer and tissue. Heparin in the serosal buffer had anti-Xa and anti-IIa activity. Decreasing the pH of the mucosal buffer to 4.0, decreased the lag period for PD. Decreasing the concentration of UFH resulted in less pronounced changes in PD and less heparin in the serosal buffer. Changes in PD suggest that heparin moves across the mucosa. Presence of heparin in the serosal buffer and mucosal tissue, indicate that heparin crosses rat gastric mucosa. A stable I(sc) indicates passive diffusion contributes to heparin movement. The stomach could be a site for oral heparin absorption.
Moazed
Bita
B
Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4, Canada.
Hiebert
Linda M
LM
D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006493:Heparin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D006493:Heparin