Microcirculation and Leg Ulcers

Philip D. Smith
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Abstract

Dr. Philip Coleridge Smith, Department of Surgery, Middlesex Hospital, Mortimer Street, London W1N 8AA (UK), Tel. +44 171 3809412, Fax +44 171 3809413, E-Mail p.coleridgesmith@ucl.ac.uk Venous diseases of the lower limb are very common, with a prevalence of 10-20% of the adult population, and in Europe drugs are widely used to treat these. Many of these drugs were developed and used without detailed knowledge of their mechanisms of action. Recent research has uncovered many details of the biological processes at work in blood vessels. This had lead to a revolution in the understanding of ischaemia and atheroma formation. It has been found that many of the mechanisms responsible for ischaemia reperfusion injury are also involved in the development of skin damage and ulceration in patients with chronic venous disease of the leg. The symposium included in the pages that follow was originally presented to the Vlth World Microcirculation Congress in Munich on 29th August 1996. The articles in it review the effect of a widely used phlebotropic drug. Daflon® 500 mg, on several models of tissue ischaemia. The animal models selected are well known and widely used in the study of ischaemia as well as in testing various interventions to protect against ischaemia reperfusion injury. The data show that there is a substantial, easily measurable effect of Daflon 500 on endothelial-leucocyte interactions caused by ischaemia reperfusion injury. These are similar to the effects of some well-known methods of preventing endothelial injury, such as the use of antibodies to the leucocyte ligand CD1 lb. These are certainly interesting and unexpected findings. The severity of ischaemia reperfusion injury is generally very great and important cellular mechanisms must be inhibited to modify this process. It is fascinating to see that Daflon 500 has the ability to achieve measurable effects in such models. Tissue damage caused by venous disease is usually more insidious, slowly destroying the endothelium of the skin microcirculation in the leg over a number of years. However, it is now clear that many of the same processes are at work in patients with ambulatory venous hypertension to produce damage in the skin microcirculation. It would be very interesting to discover whether Daflon 500 could modify the same mechanisms in patients with venous disease. Clearly different methods of investigation would be required, but such studies would confirm the reasons for the efficacy of Daflon 500 in the management of venous disease. The last two papers in this symposium discuss the results of treatment in 2 different groups of patients. In neither group has the leucocyte response been assessed in detail, although a number of rheological factors have been measured by Dr. Le Dévéhat. He investigated a group of patients with mild venous symptoms and recorded a small influence of Daflon 500 on the parameters he investigated. In contrast Prof. Nicolaides reports the efficacy of Daflon 500 on venous ulcer healing. Despite the fact that only a small group of patients was studied, large differences in the rate of ulcer healing between the placeboand Daflon 500-treated groups were observed. Although this pilot study was only of 8 weeks duration, the preliminary data from this
微循环和腿部溃疡
Philip Coleridge Smith医生,米德尔塞克斯医院外科,莫蒂默街,伦敦W1N 8AA(英国),电话+44 171 3809412,传真+44 171 3809413,E-Mail p.coleridgesmith@ucl.ac.uk下肢静脉疾病非常常见,患病率为成人人口的10-20%,在欧洲广泛使用药物治疗这些疾病。这些药物中有许多是在没有详细了解其作用机制的情况下开发和使用的。最近的研究揭示了血管中起作用的生物过程的许多细节。这导致了对缺血和动脉粥样硬化形成的理解的革命。研究发现,导致缺血再灌注损伤的许多机制也参与了腿部慢性静脉疾病患者皮肤损伤和溃疡的发展。下文所载的专题讨论会最初是1996年8月29日在慕尼黑举行的第五届世界微循环大会上提出的。本文综述了一种广泛应用的促静脉药物的作用。Daflon®500毫克,对几种组织缺血模型。所选择的动物模型是众所周知的,并广泛用于缺血研究以及测试各种干预措施以防止缺血再灌注损伤。数据显示,Daflon 500对缺血再灌注损伤引起的内皮-白细胞相互作用有显著的、易于测量的影响。这些类似于一些众所周知的预防内皮损伤的方法,如使用白细胞配体cd1lb抗体。这些当然是有趣和意想不到的发现。缺血再灌注损伤的严重程度通常非常大,必须抑制重要的细胞机制来改变这一过程。看到Daflon 500能够在这样的模型中实现可测量的效果是很有趣的。静脉疾病引起的组织损伤通常更隐蔽,在数年的时间里慢慢破坏腿部皮肤微循环的内皮。然而,现在很清楚,许多相同的过程在动态静脉高压患者中起作用,导致皮肤微循环受损。这将是非常有趣的发现是否达芙伦500可以改变相同的机制,病人的静脉疾病。显然需要不同的调查方法,但这些研究将证实Daflon 500治疗静脉疾病有效的原因。本次研讨会的最后两篇论文讨论了两组不同患者的治疗结果。在这两组中,白细胞反应都没有被详细评估,尽管许多流变学因素已经被Le dastimazhat博士测量。他调查了一组有轻微静脉症状的患者,并记录了Daflon 500对他所调查的参数的小影响。相反,Nicolaides教授报告了Daflon 500对静脉溃疡愈合的疗效。尽管只有一小部分患者被研究,但在安慰剂组和Daflon 500治疗组之间,溃疡愈合率有很大差异。虽然这项初步研究的持续时间只有8周,但从这项研究中获得的初步数据
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