Intrapulmonary heparin. A new procedure for anticoagulant therapy.
Heparin was administered by the intrapulmonary route to dogs, mice, and human volunteers. In all species, a single administration of a large quantity of heparin via the lung resulted in a prolonged state of moderate hypocoagulability (3 days in dogs, 14 days in man) due to the production of a sustained low concentration of heparin in plasma. The lengthening of clotting-time and duration of this response increased with dosage. Effective doses are above 8 mg (1300 units) per kg body-weight. Examination of the lungs, body-fluids, and tissues shows that the heparin is cleared rapidly from the lung and enters a body cellular compartment (probably the macrophages) from which it is slowly released to plasma. No evidence was found (symptomatic or on gross or histological postmortem examination) of haemorrhage or any heparin-related pathological change indicating either immediate or long-term toxic effects in the lung or other tissues. Suggestions are made for the clinical use of the unique features of anticoagulant treatment by intrapulmonary heparin.