Background: Whole-body exercise provides protection against endothelial ischaemia-19 reperfusion (IR) injury. In this crossover study, we examined the effects of 1) single bout of 20 local exercise (handgrip, squats) on endothelial responses to IR, and 2) if 7 days of daily local 21 exercise bolsters these effects in individuals with cardiovascular disease (CVD) risk factors. 22 Methods: Fifteen participants (9 women, 58±5 years, ≥2 CVD risk factors) attended the 23 laboratory for 6 visits. Subsequent to familiarization (visit 1), on visit 2 (control) brachial 24 artery flow-mediated dilation (FMD) was measured before and after IR (15-minutes upper-25 arm ischemia, 15-minutes reperfusion). One week later, participants were randomized to 4x5-26 min unilateral handgrip (50% maximal voluntary contraction, 25 rpm) or squat exercises (15 27 rpm), followed by IR plus FMD measurements. Subsequently, home-based exercise was 28 performed (six days), followed by another visit to the laboratory for the IR protocol plus 29 FMD measurements (18-24 h after the last exercise bout). Following a two-week washout 30 period, procedures were repeated with the alternative exercise mode. 31 Results: For a single exercise bout, we found a significant IR injury*exercise mode 32 interaction (P0.05). 38 Conclusions: Single bouts of dynamic, local exercise (handgrip, squats) provides remote 39 protection against endothelial IR-induced injury in individuals with CVD risk factors, with 40 one-week daily, home-based exercise preserving these effects for up to 24h following the last 41 exercise bout
