Cyclooxygenase-dependent contribution to increased flow mediated dilatation following a week of repeated ischemic preconditioning

PURPOSE: Ischemic preconditioning (IPC) and remote ischemic preconditioning (RIPC) independently enhance endothelial function and flow mediated dilation (FMD); yet the underlying mechanisms remain incompletely defined. This study investigated the contribution of cyclooxygenase (COX) dependent vasodilators to FMD before and after repeated IPC and RIPC. METHODS: 21 healthy participants underwent Radial artery FMD assessments before and after oral aspirin (600 mg) ingestion for COX inhibition. Participants then completed a one-weeklong alternate day unilateral IPC protocol (four repeated cycles of 5-minute ischemia and 5-minute reperfusion). 24 h after the final IPC session, FMD responses were reassessed before and after aspirin ingestion. RESULTS: Prior to IPC treatment, aspirin failed to significantly reduce FMD in both Radial arteries. Following IPC treatment, the now significantly increased FMD of the ipsilateral arm (9.50 ± 4.58% (mean ± standard deviation); p = 0.006) attenuated with aspirin (4.55 ± 2.68%; p = 0.002). Absolute difference in FMD % before and after aspirin ingestion increased from 1.48 ± 5.05% pre-IPC to 4.95 ± 4.96% (p = 0.016) post-IPC. In the contralateral (RIPC) arm, increased FMD % also attenuated with aspirin (p = 0.006) but this statistical significance was not seen following correction for shear rate. Nonetheless, absolute difference in FMD % before and after aspirin increased from 0.04 ± 4.05 pre-RIPC to 2.27 ± 3.60% (p = 0.043) post-RIPC. CONCLUSION: One week of alternate day IPC improves contribution of COX-derived vasoactive mediators to FMD. Contributions to RIPC driven improvements in FMD require further investigation.