Jaques L B, Mahadoo J, Kavanagh L W
Lancet. 1976 Nov 27;2(7996):1157-61. doi: 10.1016/s0140-6736(76)91679-2.
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.
通过肺内途径给狗、小鼠和人类志愿者注射肝素。在所有物种中,经肺单次给予大量肝素会导致中度低凝状态持续延长(狗为3天,人为14天),这是由于血浆中肝素持续处于低浓度状态。凝血时间的延长及这种反应的持续时间随剂量增加而延长。有效剂量高于每千克体重8毫克(1300单位)。对肺、体液和组织的检查表明,肝素从肺中迅速清除,并进入机体细胞区室(可能是巨噬细胞),然后从该区域缓慢释放到血浆中。未发现出血迹象或任何与肝素相关的病理变化(无论是症状性的,还是大体或组织学尸检结果),表明肺或其他组织存在即时或长期毒性作用。文中针对肺内注射肝素进行抗凝治疗的独特特性在临床应用方面提出了建议。