The Impact of Age and Fitness on Reperfusion Injury and Ischemic Preconditioning to Prevent This Injury

Rationale: Ischaemic preconditioning (IP) refers to the reduction of ischemia-reperfusion injury induced by a brief preceding period of ischemia. Also the arterial endothelium can be protected by IP. Several studies performed in animals and humans have demonstrated that the protective effects of IP are attenuated with aging. However, no previous study directly examined the underlying mechanisms of this observation. Possibly, the reduced protective effect of IP with aging relates to a direct effect on the endothelium, consequently leading to an attenuated ability of IP to prevent endothelial dysfunction after ischaemia reperfusion injury. Several previous studies failed to demonstrate the ability of pharmacological stimuli to mimic the beneficial effects of IP in aged vessels. Restoration of the age-related reduction in effectiveness of IP may be possible through exercise training. In aged animals, physical training restores the efficacy of ischemic preconditioning. Indirect evidence indicates that physical activity, independent of other cardiovascular risk factors, protects against a occurrence as well as the severity of a myocardial infarction in humans. Although this suggests that physical activity may beneficially influence the age-related reduction in IP, no previous study provided direct evidence for this hypothesis. Objective: To examine the impact of age and physical fitness on the ability of ischaemic preconditioning to protect endothelial damage in response to ischaemia reperfusion injury in healthy humans. A secondary objective is to explore the role of Toll-like receptor (TLR) signalling in the induction of IP in young and old subjects.