Neutrophils may contribute to the morbidity and mortality of claudicants

Abstract

Peripheral arterial occlusive disease is a common cause of morbidity in middle-aged men; 5 per cent of those aged over 50 years suffer from intermittent claudication. While claudication itself is not fatal, claudicants have a mortality rate approximately three times that of non-claudicating men of the same age, mainly from cardiovascular disease. This review examines the evidence for involvement of the neutrophil in this increased mortality and describes the possible pathogenesis. It also discusses how treatment of claudication may modify neutrophil behaviour, reducing subsequent mortality and morbidity rates.

Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication

“…Circulating neutrophil levels have been shown to increase after exercise claudication (17,35) and we previously showed (21) significant neutrophil infiltration into skeletal muscle after contractile claudication. In this study, we used cyclophosphamide to reduce neutrophil infiltration.…”

Preprocedural neutrophil count predicts outcome in patients with advanced peripheral vascular disease undergoing percutaneous transluminal angioplasty

“…29,30 It is through plaque disruption and microvessel plugging that neutrophils could play an active role in the initiation and progression of tissue ischemia. 31 This was an observational study, and as a result we were unable to adjust for all potentially confounding variables. Although a single baseline measurement of total and differential WBC count was used, it is plausible that serial measurement with assays of cellular activation or other inflammatory marker such as CRP and interleukin-6 may yield a different picture.…”

Augmentation of the Neutrophil Respiratory Burst Through the Action of Advanced Glycation End Products

“…Evidence also suggests that even controlling for other factors, a higher blood leukocyte count and especially the granulocytic component, predicts a greater likelihood of future vascular events. Infection is similarly often found preceding the development of ischemic events (27,28). In comparing neutrophils from healthy individuals with those from patients with stable and unstable coronary artery disease, there exists a gradation of progressive neutrophil activation that may provide a pathophysiological milieu for the progression of stable to unstable coronary artery disease.…”

“…Activated neutrophils release toxic chemicals including ROS and proteolytic enzymes that damage the endothelium and basement membrane. ROS release also causes lipid oxidation and initiates platelet activation/aggregation; neutrophils may thus be involved in the primary pathogenesis and progression of occlusive vascular disease (27,28).…”