Repeated Exercise Induces Release of Soluble P-Selectin in Patients with Intermittent Claudication

Abstract

SummaryControversy exists as to whether exercise in patients with intermittent claudication causes a harmful biochemical effect associated with an ischaemia-reperfusion injury of skeletal muscle. We report on exercise-induced changes in neutrophil activation, soluble P-selectin and von Willebrand factor in 34 patients with intermittent claudication and 12 matched controls.Von Willebrand factor (vWF) showed a cyclical pattern of response to exercise in control subjects (rising from 103 ± 8 to 119 ± 7 U/dl); claudicants did not show this pattern but had higher levels of vWF throughout (p <0.03). There was no consistent pattern of response in neutrophil hydrogen peroxide production to exercise in either claudicants or control subjects. Soluble P-selectin levels increased after exercise, but this only reached statistical significance after repeated exercise in claudicants (rising from 320 ± 28 to 357 ± 28 ng/ml). This rise in soluble P-selectin after exercise may indicate progressive platelet activation which may contribute to the excess cardiovascular mortality that claudicants are prone to.

Measurement of ischaemia–reperfusion in patients with intermittent claudication using NMR‐based metabonomics

“…the exercise metabolome) was studied separately for each treatment period (study appointments A, B and C). Clustering was not evident in healthy subjects (results not shown), which is in line with previous studies [7,23,24]. Figure 2 depicts the PC-DA models, based on plasma CPMG NMR profiles from the claudicants obtained in periods A and C.…”

“…The vitamin intervention led to an overall decrease in F2-isoprostane concentration, and a statistically significant effect of exercise was no longer observed. As expected [7,23,24], no significant effects on F2-isoprostane concentrations were observed in the control group.…”

“…The study design involved 14 claudicants and three healthy volunteers, who were subjected to a walking test before and after the intake of vitamins and after a washout period. As previous studies have shown that a walking test does not have a metabolic effect on healthy subjects (7,23,24), their number was kept relatively small. The choice of the biochemical markers, summarised in Table 1, was based on accepted mechanisms involved in IR.…”

Effects of iloprost on blood rheology and tissue perfusion in patients with intermittent claudication: Results of a double-blind placebo-controlled study

“…Platelet activation is known to in¯uence BV [26] and our pre-treatment ®nding of an increase in soluble Pselectin after exercise may indicate early, reversible platelet activation in claudication [4], concurring with Kirkpatrick et al [22]. As P-selectin is not normally expressed on resting platelets, its detection on the platelet surface is considered an index of secretion since it is contained in platelet a-granules [41].…”

Impairment of microcirculation and energy metabolism in intermittent claudication: beneficial effects of exercise training

“…Furthermore activated leukocytes release thromboxane A2, which in addition to be a vasoconstrictor, promotes platelet aggregation [27], so inducing the phenomenon of platelet plugging. To this phenomenon in claudicants may also participate overexpression of P-selectin [28,29] which mediates platelet-endothelium interaction [30]. Consistent with the observation by Neumann et al [26], our group observed that in the claudicant limb, but not in the healthy legs of the control group, maximal exercise increased the transfemoral venous-arterial difference of the neutrophil myeloperoxidase (MPOx) content [31], an index of neutrophil activation and a well established marker of inflammation [32].…”