The Effectiveness Of Ischemic Preconditioning In Older Physically (in)active Males

Abstract

Reperfusion is critical for the survival of ischemic tissue, but causes significant additional damage to the endothelium (ischemia-reperfusion [IR]). Ischemic preconditioning (IPC) refers to short repetitive episodes of ischemia, which has demonstrated to reduce IR injury. The protective effects of IPC against endothelial IR injury are attenuated with aging. Possibly, regular physical activity is able to 1) attenuate endothelial IR, and 2) restore effectiveness of IPC in older humans. PURPOSE: To compare endothelial IR-injury and the effectiveness of IPC to protect against endothelial IR-injury between older lifelong physically active versus inactive males. METHODS: We included 11 older athletes (63±4 years, >5 exercise hours/week) and 3 inactive controls (69±6 years, <1 exercise hours/week). We measured brachial artery endothelial function before and after IR injury using flow-mediated dilation (FMD). IR-injury was induced by 20-minute ischemia followed by 20 minutes of reperfusion. Prior to IR-injury, subjects underwent SHAM (35-minute rest) or IPC (3 cycles of 5-minute cuff inflation to 220 mmHg). The order of SHAM and IPC was randomly assigned to the participants. RESULTS: FMD% did not differ between athletes and inactive controls at baseline for SHAM (4.5±4.4% vs. 4.1±2.4%, p=0.87) or IPC (5.1±3.1% vs. 3.3±1.1%, p=0.37). IR-injury showed no significant decrease in FMD% in athletes (FMDpre 4.5±4.4% vs. FMDpost 3.0±2.0%, p=0.32), whereas FMD% markedly decreased in inactive controls (FMDpre 4.1±2.3% vs. FMDpost 0.5±2.5%, p=0.036). Applying IPC before IR-injury did not alter the change in %FMD in both athletes (FMDpre 5.1±3.2% vs. FMDpost 2.8±3.3%, p=0.17) and controls (FMDpre 3.3±1.1% vs. FMDpost 1.5±2.2%, p=0.19). No differences were observed in %FMD change between SHAM and IPC in athletes and inactive controls. CONCLUSIONS: Athletes demonstrate smaller endothelial IR-injury compared to their physically inactive peers. The cardio-protective effects of regular exercise training may, in part, relate to attenuating endothelial IR-injury. Finally, lifelong regular exercise training seems unable to alter the age-related attenuated efficacy of IPC against endothelial IR-injury.