A strain difference in anticoagulant response to subcutaneous administration of heparin in mice

Abstract

A significant difference in anticoagulant response to subcutaneous administration of heparin between two strains of mice has been discovered. Agouti C3H mice had a faster, greater and more prolonged response than albino Swiss mice. On addition of heparin to the blood of the two strains in vitro , identical clotting times were obtained. There was no significant difference in anticoagulant response to intravenous injection in the two strains of mice for a quantity of heparin which gave blood levels similar to those obtained with subcutaneous injection in the Swiss mice. The difference in response to subcutaneous heparin in these two strains of mice can be obtained at different injection sites. The C3H mice also showed greater anticoagulant response than the Swiss mice, after introducing heparin together with citric acid into the small intestine. Injection of 35S-heparin in the foot pad subcutaneously demonstrated that the removal of radioactivity from the injection site was faster and the plasma level of radioactivity was higher in C3H mice than Swiss mice. These results indicate a strain difference in the transfer of heparin to the circulation after subcutaneous or intestinal administration and suggest this provides a suitable animal model for study of absorption mechanisms for heparin.