Activation and decreased deformability of neutrophils after intermittent claudication.

Abstract

This study investigated local alterations in neutrophil activation and deformability after intermittent claudication. In 17 patients with one-sided peripheral arterial occlusive disease, neutrophil count, proportion of activated neutrophils (by nitro blue tetrazolium test), and neutrophil filterability as a measure of passive deformability were assessed in the femoral arterial and venous blood of the diseased leg and in the femoral venous blood of the healthy leg (n = 10). The values were obtained at rest, immediately after claudication, and 10 minutes after claudication induced by repetitive toe stands. Immediately after exercise, the arterial and venous blood differences in the diseased leg were 1) neutrophil count, 9% (95% confidence interval [CI], 5-14%; relative increase in the venous blood compared with arterial blood); 2) the proportion of activated neutrophils, 26% (CI, 10-42%); and 3) the neutrophil filterability, -10% (CI, -4% to -15%). At rest and 10 minutes after exercise, neutrophil parameters did not differ significantly between the femoral arterial and venous blood. Furthermore, no arterial and venous blood differences in the neutrophil parameters were found in the healthy leg. In addition to local changes, systemic changes occurred immediately after exercise. In the femoral arterial blood, the total neutrophil count had risen by 13% (CI, 8-18%), the proportion of activated neutrophils had risen by 41% (CI, 25-58%), and average neutrophil rigidity had risen 17% (CI, 11-22%) compared with the values obtained before exercise. At 10 minutes after exercise, all neutrophil parameters were still elevated. We conclude that even short periods of ischemia, as in intermittent claudication, cause local alterations in neutrophil function and distribution.

Effects of oral N-acetylcysteine on walking capacity, leg reactive hyperemia, and inflammatory and angiogenic mediators in patients with intermittent claudication

“…One prevailing view is that this abnormal response stems in part from ischemia-induced activation of inflammatory cells in the affected legs (37). As first shown by Neumann and coworkers (37) and later by others (7,8), exercise in claudicants increases total neutrophil number and the proportion of activated neutrophils in the venous blood draining from the affected leg, whereas no changes are observed in the unaffected leg. We reasoned that NAC would improve leg vascular dysfunction in patients with IC, thereby reducing exercise-induced ischemia and the consequent inflammatory response.…”

“…This proinflammatory state is particularly exacerbated by exercise in symptomatic patients. A single bout of maximal exercise in patients with IC triggers robust increases in inflammatory cytokines, vascular adhesion molecules, and markers of oxidative damage (37,54,60,61). Among other consequences, repeated exposure to these injurious events is thought to promote functional and structural abnormalities in skeletal muscle (13,24,44) and endothelial dysfunction (57).…”

Inflammation in Peripheral Artery Disease

“…176,177 In addition to these systemic responses, exercise triggers acute local inflammation. In 17 patients with unilateral PAD, Neumann et al 178 found that immediately after claudication, total neutrophil number, neutrophil flexibility, and the proportion of activated neutrophils were higher in the venous blood draining from the affected leg than in arterial blood. These venous-arterial differences were not observed from the circulation of the contralateral unaffected exercising leg.…”

Acquired skeletal muscle metabolic myopathy in atherosclerotic peripheral arterial disease

“…Malondialdehyde concentrations are markedly elevated in PAD, and increase further with exercise. 38,39 Additionally, circulating neutrophils from patients with PAD are activated, 40 providing an additional source of systemic oxidative stress.…”