A single large dose of heparin (2000 units/kg) was administered to dogs by intratracheal instillation. Whole blood clotting times and plasma heparin concentrations were measured at intervals. At each interval the calculated dose of protamine required to neutralize the circulation heparin was given intravenously and the measurement of plasma heparin concentration repeated. The authors found that the whole blood clotting time was prolonged for 24 to 48 hours and there was a detectable concentration of heparin in the plasma for 96 hours. On each occasion the protamine eliminated the circulation heparin, but more heparin continued to enter the circulation. It is hypothesized that after rapid absorption from the lung, heparin is stored temporarily in a cellular pool throughout the body and then released into the circulation. At any given time the anticoagulant effect can be reversed by intravenously administered protamine sulfate if this should become necessary, but repeated administration would be required. Intrapulmonary heparin may have useful clinical applications but further clinical and laboratory investigations are required.

Heparin releases diamine oxidase (DAO, histaminase) from binding sites in the intestinal vasculature. Histamine is involved in a number of pathological lesions. In this study we have examined the effect of intrapulmonary administration of heparin on plasma DAO activity in mice. For comparative purposes the same parameter was measured following the administration of an intravenous heparin regimen. The time course and dose-response were examined with the two heparin regimens. The doses of heparin were based on appropriate clinical equivalents. Both heparin regimens showed a dose dependent response (correlation coefficientr=0.9). The dose of intrapulmonary heparin (10 mg/kg) was 12 times greater than the dose injected intravenously but the DAO response lasted 48 times longer than that obtained from the intravenous heparin regimen.

Several hypotheses have been advanced for disorders of lipid metabolism such as atherosclerosis. However, these have not led to any significant means of control or cure. A reappraisal of the situation in the light of recent observations has led us to believe that lipid absorption and redistribution is under the control of a histamine-glycosaminoglycan-histaminase system which regulates vascular permeability. Failure of this control mechanism may lead to pathological conditions.

The lipoprotein lipase (LPL) activity obtained from the intrapulmonary administration of 2-10 mg of heparin in mice was compared with the same parameter measured for intravenously administered heparin. The doses administered were based on appropriate clinical equivalents. A relatively large dose of intrapulmonary heparin produced a peak LPL activity which was a third of the maximum response obtained from a small dose of i.v. heparin. This was followed by a moderate LPL activity (twice the control level) which persisted for the next 4 days while the response obtained from i.v. administered heparin lasted only 2 h. Both the intrapulmonary and the i.v. administration of heparin produced dose-dependent increases in plasma LPL activity (correlation coefficient r = 0.9). This study indicates that intrapulmonary heparin causes a prolonged antilipemic effect.

Annals of the New York Academy of SciencesVolume 370, Issue 1 p. 650-655 VASCULAR DISTRIBUTION OF INTRATRACHEALLY ADMINISTERED HEPARIN* J. Mahadoo, J. Mahadoo Department of Surgery, College of Medicine, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0Search for more papers by this authorL. M. Hiebert, L. M. Hiebert Department of Surgery, College of Medicine, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0Search for more papers by this authorC. J. Wright, C. J. Wright Department of Surgery, College of Medicine, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0Search for more papers by this authorL. B. Jaques, L. B. Jaques Department of Surgery, College of Medicine, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0 Department of Oral Biology, College of Dentistry, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0Search for more papers by this author J. Mahadoo, J. Mahadoo Department of Surgery, College of Medicine, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0Search for more papers by this authorL. M. Hiebert, L. M. Hiebert Department of Surgery, College of Medicine, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0Search for more papers by this authorC. J. Wright, C. J. Wright Department of Surgery, College of Medicine, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0Search for more papers by this authorL. B. Jaques, L. B. Jaques Department of Surgery, College of Medicine, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0 Department of Oral Biology, College of Dentistry, University of Saskatchewan Saskatoon, Saskatchewan, Canada S7N 0X0Search for more papers by this author First published: June 1981 https://doi.org/10.1111/j.1749-6632.1981.tb29771.xCitations: 12 † This work was supported by funds from the Saskatchewan Heart Foundation. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume370, Issue1Contributions to HemostasisJune 1981Pages 650-655 RelatedInformation