Dormandy J A
St. George's Hospital and Medical School, London, England.
J Cardiovasc Pharmacol. 1995;25 Suppl 2:S61-5. doi: 10.1097/00005344-199500252-00013.
In terms of prevalence, total cost and morbidity, venous leg ulcers are probably by far the most important type of ulcerations in the leg. The macrocirculatory defect leading to a raised ambulatory venous pressure is now accepted as a common initial pathologic pathway. Most current treatment modalities, such as surgery or external compression, are designed to control the macrovascular defect. However, it is the microcirculatory consequences of the venous hypertension that give rise to the trophic skin changes and ultimately to ulceration. At this microcirculatory level, pharmacotherapy may be a useful adjunct in the treatment of venous leg ulcers. The microcirculatory pathophysiologic changes include decreased fibrinolytic activity, elevated plasma fibrinogen, microcirculatory thrombi, and inappropriate activation of the white blood cells. The oxidative burst from the activated white cells probably plays a key role by releasing locally leukocyte-derived free radicals, proteolytic enzymes, cytokines, platelet-activating factor, and a number of other noxious mediators. An important additional component in recalcitrant venous ulcers is co-existing arterial disease, which is probably present in 15-20% of cases. Decreased arterial perfusion pressure will further aggravate the ischemic changes caused by the venous hypertension. Pentoxifylline downregulates leukocyte activation, reduces leukocyte adhesion, and also has fibrinolytic effects. A number of clinical studies have therefore been carried out to examine the clinical efficacy of pentoxifylline in treatment of venous leg ulcers. Probably the largest published placebo-controlled, double-blind randomized study was reported in 1990. In this study, 80 patients received either pentoxifylline 400 mg three times a day orally or matching placebo for 6 months or until their reference ulcer healed if this occurred sooner. Complete healing of the reference ulcer occurred in 23 of the 38 patients treated with pentoxifylline compared to 12 of the 42 patients treated with placebo. The odds ratio in favor of pentoxifylline was 1.81 (95 confidence intervals 1.20-2.71).
就患病率、总成本和发病率而言，腿部静脉溃疡可能是目前腿部最重要的溃疡类型。导致动态静脉压升高的大循环缺陷现在被认为是常见的初始病理途径。目前大多数治疗方式，如手术或外部压迫，旨在控制大血管缺陷。然而，正是静脉高压的微循环后果导致了营养性皮肤变化并最终导致溃疡形成。在这个微循环层面，药物治疗可能是治疗腿部静脉溃疡的有用辅助手段。微循环病理生理变化包括纤溶活性降低、血浆纤维蛋白原升高、微循环血栓形成以及白细胞的不适当激活。活化白细胞产生的氧化爆发可能通过释放局部白细胞衍生的自由基、蛋白水解酶、细胞因子、血小板活化因子和许多其他有害介质发挥关键作用。顽固性静脉溃疡的一个重要额外因素是并存的动脉疾病，可能在15%至20%的病例中存在。动脉灌注压降低会进一步加重静脉高压引起的缺血性变化。己酮可可碱可下调白细胞活化、减少白细胞黏附，还具有纤溶作用。因此，已经进行了多项临床研究来检验己酮可可碱治疗腿部静脉溃疡的临床疗效。1990年报道了可能是已发表的最大规模的安慰剂对照、双盲随机研究。在这项研究中，80名患者每天口服三次400毫克己酮可可碱或匹配的安慰剂，持续6个月，或者如果参考溃疡更快愈合则持续到愈合。接受己酮可可碱治疗的38名患者中有23名参考溃疡完全愈合，而接受安慰剂治疗的42名患者中有12名愈合。支持己酮可可碱的优势比为1.81（95%置信区间1.20 - 2.71）。
