A New Method of Administering Heparin. ∗

Abstract

In the course of studies on experimental subacute bacterial ednocarditis, attempts were made to produce the disease in heparinized rabbits. The methods for heparinizing humans, namely, by continuous venoclysis or by repeated intravenous injections, were virtually impossible of adaptation for the rabbit. However, rabbits will develop and maintain a prolonged coagulation time over a protracted period with repeated subcutaneous injections of heparin, the average daily requirement being about 45 mg of commercial heparin† administered in fractional doses. 1

In order to eliminate the disturbing abrupt rises, sharp peaks and unpredictable drops in coagulation time as well as the technical difficulties incidental to fractional daily dosage, a simpler means had to be devised for continuous heparinization by the subcutaneous route.

In view of the success obtained with pellet and capsule implantation of hormones, 2 similar experiments were pursued with heparin. Pellets containing 50 mg and glass capsules tightly packed with 100 mg of heparin were implanted under sterile precautions subcutaneously or subfascially through a small skin incision. While rabbits could be heparinized in this fashion, this approach had to be abandoned for the following reasons: The results with glass capsules were erratic. On some occasions a spectacular but shortlived effect was obtained: at other times, the results were negative and when the capsule was removed subsequently it was discovered that practically none of the heparin had been acted upon.

Additional shortcomings were: The necessity for instrumental procedure; the rapid absorption of pellets with resultant inordinately delayed coagulation time and subsequent precipitate drop; the presence at times of local hemorrhage and the obvious impracticability of sustaining heparin effects over prolonged periods.