Ischemic preconditioning is defined as the development of tolerance to ischemia-reperfusion
injury by a previous short bout of ischemia resulting in a marked reduction in infarct size.
This mechanism can be mimicked by several pharmacological substances such as acetylcholine
and adenosine.
To detect ischemia-reperfusion injury in humans in vivo Kharbanda et al. developed a method
in which endothelial dysfunction represents the effects of ischemic preconditioning. This
method, however, uses acetylcholine to measure endothelial function before and after forearm
ischemia. We, the investigators at Radboud University, hypothesize that the use of
acetylcholine in this model reduces ischemia-reperfusion injury. Therefore, we will compare
this protocol with a protocol in which endothelial function is only measured after ischemia.
We expect an increase in ischemia-reperfusion injury when endothelial function is only
measured after the forearm ischemia.
After determining the optimal method to measure ischemia-reperfusion injury of the vascular
endothelium we will determine the effect of acute and chronic caffeine, an adenosine receptor
antagonist, on ischemic preconditioning. With this study we expect to find that adenosine
mimics ischemic preconditioning of the vascular endothelium. Moreover, we expect to find that
acute caffeine intake reduces ischemia-reperfusion injury whereas chronic caffeine intake
does not. This study will increase our knowledge about the mechanism of ischemic
preconditioning and may also provide leads to exploit this endogenous protective mechanism in
a clinical setting.