Pharmacological reduction of the systemically damaging effects of local ischaemia

Abstract

Many patients with intermittent claudication are encouraged to exercise. However, transient exercise-induced muscle ischaemia results in systemic vascular endothelial injury associated with increased vascular permeability manifest as an increase in urinary albumin excretion. Repetitive systemic vascular endothelial injury leads to accelerated atherogenesis and may explain the high cardiovascular mortality rate of claudicants. Oxpentifylline, a haemorheological agent, has recently been shown to prevent vascular endothelial injury in animal models. A double-blind, placebo-controlled, cross-over trial was undertaken to determine the effect of oxpentifylline on exercise-induced systemic vascular endothelial injury in 20 claudicants. Urinary albumin, expressed as a creatinine ratio (ACR), was measured before and 1 and 2 hours after standardised exercise following 1 week treatment with either active drug or placebo. Oxpentifylline reduced the median (range) 1 hour post exercise increase in ACR from 0.35 (-0.46-12.72) to 0.02 (-6.00-14.10) mg/mmol. (p = 0.030, z = 2.2 Wilcoxon rank sign test). These results confirm that local ischaemia is associated with a potentially deleterious systemic effect and that it may be possible to attenuate this pharmacologically. The clinical significance of this is yet to be determined.