Influence of cardiovascular risk factors on remote ischemic preconditioning

A powerful therapy against microvascular endothelial ischemia-reperfusion injury is remote ischemic preconditioning (rIPC), which triggers tissue protection by exposing a limb to small cycles of vascular occlusion. Animal models indicate that CVD risk factors reduce the protective benefits of ischemic conditioning. However, there are no human studies investigating how a burden of risk factors interferes with rIPC to prevent endothelial injury. The purpose of the present study was to determine the influence of risk factor burden on the capacity of rIPC to prevent endothelial reperfusion injury in humans.;Twenty-two (age: 45+/-14 yr., BMI: 31+/-8 kg/m2) sedentary adults (12 lower burden: ≤2 risk factors; 10 raised burden: 3-5 risk factors) were studied. Digital arterial tonometry (EndoPAT 2000, Itamar Medical Inc.) was used to assess microvascular endothelial vasodilation during reactive hyperemia before and after 65 min of left arm reperfusion injury (20 min brachial artery ischemia followed by 45 min reperfusion) that was preceded by rIPC (right arm: 3X5 min ischemia/reperfusion). All subjects provided written informed consent according to the Internal Review Board guidelines at South Dakota State University.;Repeated measures ANOVA was used to assess group differences between the reactive hyperemia index (RHI) before and after reperfusion injury. Statistical significance was set at P<0.05.;In lower burden subjects, rIPC was able to prevent endothelial reperfusion injury. The RHI following endothelial injury increased from baseline by 23% (from 2.1+/-0.4 to 2.5+/-0.5, P=0.072). In contrast, the RHI (baseline: 2.3+/-0.9) was significantly reduced by 25% despite induction of protection by rIPC (1.8+/-0.7) in the raised burden subjects (P=0.05). Between groups, the RHI after rIPC and endothelial injury was significantly different (P=0.008).;Microvascular endothelial injury was prevented when preceded by rIPC in the lower burden subjects. Remote IPC failed to protect against endothelial injury in the raised risk burden subjects. CVD risk factors appear to disrupt the protective properties of ischemic conditioning in humans.