Test-Retest Reliability of Endothelial Ischemia-Reperfusion Injury in Healthy Young Adults

Ischemia-reperfusion injury (IRI) describes the paradoxical phenomenon in which the restoration of blood flow to ischemic tissue can exacerbate damage during reperfusion. In humans, IRI can be modeled within the vascular endothelium by inducing 20 minutes of upper-arm ischemia and reperfusion. This approach transiently reduces flow-mediated dilation (FMD) of the brachial artery and is widely used to investigate mechanisms of vascular injury and evaluate cardioprotective therapies. Despite its widespread use, the test-retest reliability of this model has not been established. Therefore, we sought to quantify the inter-day reliability of IRI-induced reductions in FMD. Twenty healthy adults (10M/10F, age = 26 ± 7 years) completed two identical laboratory visits separated by no more than 7 (2 ± 2) days. During each visit, brachial artery FMD was assessed before and following IRI. Changes in FMD were analyzed using a two-way repeated measures ANOVA, and test-retest reliability was assessed via intraclass correlation coefficients (ICC 2,1 ). As expected, FMD was reduced following IRI in both visits (Visit 1: Pre = 7.3 ± 2.8%, Post = 4.4 ± 3.9%; Visit 2: Pre = 7.2 ± 2.8%, Post = 4.3 ± 3.6%, P < 0.001). The magnitude of this reduction (∆FMD) demonstrated excellent test-retest reliability (ICC = 0.88 [0.73−0.95]). Interestingly, a subset of participants demonstrated a resilient phenotype, characterized by preservation of FMD following IRI across both visits. These findings establish the test-retest reliability of the endothelial IRI model and support its use as a reliable tool for investigating mechanisms of vascular injury and evaluating potential therapies.