Endothelial sequestration of heparin administered by the intrapulmonary route
Mahadoo, J.; Hiebert, L.M.; Jaques, L.B.; Wright, C.J.
Artery 7(5): 438-447
1980
ISSN/ISBN: 0098-6127 PMID: 7213028 Document Number: 154775
To accomodate the increasing evidence of a cellular uptake of heparin, the cellular pool concept, which provides a rational explanation for the pharmacokinetics of heparin, was proposed. Heparin was administered to rats by tracheal instillation, and the plasma heparin concentration (PHC) and the endothelial heparin concentration (EHC) were measured. The PHC was measured daily for 5 days after a single dose of heparin (2000 .mu./kg). Four doses of heparin (1800, 10,000, 15,000 and 22,000 .mu./kg) were administered to different groups of rats, and 2 h later the PHC and EHC were measured. In addition, the EHC was measured at intervals for a period of 24 h in rats which received a single dose of heparin (19,000 .mu./kg). The prolonged anticoagulant response observed after intrapulmonary administration of heparin corresponds to a prolonged and moderate heparinemia (0.26-0.98 .mu./ml). A close relationship was observed between the EHC and the PHC and finally, after 24 h, the EHC was reduced to 7% of the 6 h EHC. In view of the rapid absorption of heparin from the lung and the cellular sequestration of the drug, the prolonged moderate heparinemia indicates a continued release of heparin into the circulation from a cellular pool. The relationship between the PHC and EHC, and the short half-life of heparin in the endothelial tissue suggest that perhaps the endothelium acts as a short-term storage or buffer compartment for the control of the level of heparin in the circulation.