Inhibition of experimental neointimal hyperplasia and thrombosis depends on the type of vascular injury and the site of drug administration.
Inhibition of experimental neointimal hyperplasia and thrombosis depends on the type of vascular injury and the site of drug administration.
复制标题
对实验性内膜增生和血栓形成的抑制取决于血管损伤的类型和给药部位。
DOI：
10.1161/01.cir.88.3.1215
复制
发表时间：
1993
期刊：
影响因子：
37.8
通讯作者：
Edelman,ER
中科院分区：
文献类型：
--
作者：
Rogers,C;Karnovsky,MJ;Edelman,ER
BACKGROUNDHeparin inhibits vascular smooth muscle cell proliferation in tissue culture and limits neointimal hyperplasia after experimental arterial injury but has been ineffective in reducing clinical restenosis. We examined how this discrepancy might reflect suboptimal drug-tissue interactions and/or differences in the vascular response to injury.METHODS AND RESULTSIntravenous infusion was compared with local administration of heparin to injured rabbit iliac arteries either from drug-impregnated polymeric controlled release matrices in the perivascular space or from drug-releasing endovascular stents. Occlusive thrombosis, seen in 42% of control stent-bearing arteries, and partial thrombosis were virtually eliminated by heparin delivery from any route. Intimal area 14 days after balloon withdrawal denudation alone was reduced to an equal extent by continuous systemic heparin or by perivascular heparin for the first 3 days. In contrast, endovascular stents produced more exuberant neointimal hyperplasia, the inhibition of which required continuous rather than only early heparin administration. Neither perivascular delivery limited to the first 3 days nor stent-based delivery reduced neointimal hyperplasia as effectively.CONCLUSIONSThe antiproliferative and antithrombotic effects of heparin differ markedly, depending on the type of arterial injury and the mode of drug administration. Different forms of injury may require different therapies, and complications of arterial intervention such as excessive neointimal hyperplasia and thrombosis may demand alternate therapeutic regimens. Duration, dose, and site of delivery rather than frank resistance to therapy may explain why experimentally effective antiproliferative and antithrombotic agents fail clinically.
