Abstract
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.