Factors of inflammatory, adhesiveness and thrombosis in acute lower limb ischemia and dexamethasone therapy

Abstract

Lymphocyte-to-platelet adhesion during hypoxia, tissue damage, activation of inflammation and coagulation is associated with expression of ICAM-1 membrane molecules by blood and tissue cells. At the same time, the platelet adhesion receptors determine their adherence to endothelium and recruited lymphocytes. Moreover, the role of platelets in pathogenesis of ischemic cardiovascular diseases comprises their ability to modulate both hemostasis and inflammatory reactions, which are accompanied by secretion of inflammatory mediators and some factors that promote recruitment of leukocytes to tissue damage sites. Creatine kinase activity is a sensitive marker of tissue damage and tissue ischemia. The purpose of the present study was to assess the effect of anti-inflammatory therapy with dexamethasone upon the intensity of inflammation and adhesive properties of lymphocytes, number of platelets in peripheral blood of the patients with acute lower limb ischemia (ALLI), as well as to evaluate the effectiveness of treatment.
 To study the effect of anti-inflammatory therapy, a group of 32 patients treated with dexamethasone was selected; the control group was represented by 71 patients with basic therapy, the comparison group consisted of 15 volunteers. After revascularization, all patients received antiplatelet and anticoagulant therapy. Dexamethasone infusions were carried out as a course of 4 to 6 days after reconstructive surgery. In all patients, the content of C-reactive protein in blood, the activity of creatine kinase, the content of platelets and, especially, of enlarged platelets were determined. The numbers of lymphocytes expressing ICAM-1 (CD54+) adhesion molecules were counted using immunocytochemical technique. The studies were performed before surgery and 1, 3, 5, 7, 10 days after surgery.
 During exacerbation of the limb ischemia and damage to endothelium, the accumulation of cytolysis products was noted. Expression of adhesion molecules was increased both on endotheliocytes and on inflammation effector cells, i.e., leukocytes and platelets. The adhesion molecules transmit the activating signal inside the cell, thus promoting adhesion of leukocytes and platelets to endothelium, lymphocytic-platelet adhesion, formation of parietal thrombi, and possible occlusion of damaged vessels. Increased expression of adhesion molecules is associated with activation of metabolism, inflammation, coagulation and oxidative stress. It may stimulate all hematopoietic lineages, including platelets. The involvement level of cellular reactions in pathogenesis of the disease affects effectiveness and duration of treatment, risk of recurrent thrombosis and lethal outcome. Anti-inflammatory therapy with dexamethasone contributed to earlier remission, it was associated with lower frequency of infectious and thrombotic complications, decreased mortality, and reduced duration of treatment.
 Inflammation, adhesiveness of effector cells and thrombosis are important factors in pathogenesis of acute lower limb ischemia. Additional anti-inflammatory therapy with dexamethasone contributes to earlier remission, decreased proportion of infectious and thrombotic complications, lower frequency of deaths, and reduced duration of treatment.