Muller D W, Ellis S G, Topol E J
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0022.
J Am Coll Cardiol. 1991 May;17(6 Suppl B):126B-131B. doi: 10.1016/0735-1097(91)90948-9.
The complexity of the events that culminate in intimal proliferation after arterial injury and similarities between this response and benign neoplasia suggest that conventional medical therapies will continue to be unsuccessful in preventing recurrent stenosis after percutaneous coronary revascularization. By preventing cell division after smooth muscle cell activation, antimitogenic therapy may inhibit the final common pathway in this complex chain of events and offset the apparent loss of local growth control. Colchicine, which causes metaphase arrest of cell division, has been shown in experimental studies to decrease the extent of atheromatous plaque formation and reduce the severity of arterial restenosis after balloon angioplasty. However, preliminary results from a randomized placebo-controlled clinical trial suggest that low dose colchicine (0.6 mg twice a day orally) does not prevent restenosis. The use of more potent antineoplastic agents is limited by the potential for life-threatening side effects. It is possible that these adverse effects can be averted by using novel drug delivery systems to administer antimitogenic therapy locally at the site of arterial injury or by using low dose synergistic combinations of antiproliferative agents. This review examines the potential role of antimitogenic therapy in the prevention of restenosis after coronary interventions and considers the possibility of an overlap of the therapeutic realms of interventional cardiology and medical oncology.
动脉损伤后最终导致内膜增生的事件的复杂性，以及这种反应与良性肿瘤形成之间的相似性表明，传统医学疗法在预防经皮冠状动脉血运重建术后的再狭窄方面仍将是不成功的。通过在平滑肌细胞激活后阻止细胞分裂，抗有丝分裂疗法可能会抑制这一复杂事件链中的最终共同途径，并抵消局部生长控制明显丧失的影响。秋水仙碱可导致细胞分裂中期停滞，实验研究表明，它可减少动脉粥样硬化斑块形成的程度，并降低球囊血管成形术后动脉再狭窄的严重程度。然而，一项随机安慰剂对照临床试验的初步结果表明，低剂量秋水仙碱（口服0.6毫克，每日两次）并不能预防再狭窄。使用更强效的抗肿瘤药物受到危及生命的副作用的限制。通过使用新型药物递送系统在动脉损伤部位局部给予抗有丝分裂疗法，或使用低剂量的抗增殖药物协同组合，有可能避免这些不良反应。这篇综述探讨了抗有丝分裂疗法在预防冠状动脉介入术后再狭窄中的潜在作用，并考虑了介入心脏病学和医学肿瘤学治疗领域重叠的可能性。
