Blackshear P J, Rohde T D, Varco R L, Buchwald H
Atherosclerosis. 1977 Jan;26(1):23-7. doi: 10.1016/0021-9150(77)90136-8.
Fourteen normal dogs received continuous infusions of intravenous heparin for one year by means of an implantable infusion pump. Heparin wad admistered at an overall mean rate of 666 units/kg/day, a dose sufficient to prolong the Lee-White clotting time to greater than twice normal. Eight control, animals, under the same dietary and activity regimen, received continuous infusions of bacteriostatic water for one year by means of implanted pumps. Serum cholesterol concentrations rose to 50% above control values after one month of heparin infusion, and remained significantly (P less than 0.05) elevated at this level for the remaining 11 months. Serum triglyceride levels were unchanged. A possible mechanism for this elevation resides in the known effect of heparin to increase plasma free fatty acid concentrations by its activation of lipoprotein lipase. These results may have implications for the long-term use of heparin anticoagulation in the treatment of atherosclerotic states in man.
十四只正常犬通过植入式输液泵接受了为期一年的静脉肝素持续输注。肝素的总体平均给药速率为666单位/千克/天，该剂量足以使李-怀特凝血时间延长至正常的两倍以上。八只对照动物在相同的饮食和活动方案下，通过植入式泵接受了为期一年的抑菌水持续输注。肝素输注一个月后，血清胆固醇浓度升至高于对照值50%的水平，并在接下来的11个月中一直显著（P<0.05）维持在该水平。血清甘油三酯水平未发生变化。这种升高的一种可能机制在于肝素通过激活脂蛋白脂肪酶来增加血浆游离脂肪酸浓度的已知作用。这些结果可能对肝素抗凝在人类动脉粥样硬化状态治疗中的长期应用具有启示意义。
