Menopausal stage differences in endothelial resistance to ischemia-reperfusion injury

Background: In postmenopausal women, reduced ovarian function precedes endothelial dysfunction and attenuated endothelial resistance to ischemia-reperfusion (IR) injury. We hypothesized that IR injury would lower endothelial function, with premenopausal women demonstrating the greatest protection from injury, followed by early, then late postmenopausal women. Methods: Flow-mediated dilation (FMD) was assessed at baseline and following IR injury in premenopausal (n = 11), early (n = 11; 4 ± 1.6 years since menopause), and late (n = 11; 15 ± 5.5 years since menopause) postmenopausal women. Results: There were significant group differences in baseline FMD (p = 0.007); post hoc analysis revealed a similar resting FMD between premenopausal (7.8% ± 2.1%) and early postmenopausal (7.1% ± 2.7%), but significantly lower FMD in late postmenopausal women (4.5% ± 2.3%). Results showed an overall decline in FMD after IR injury (p < 0.001), and a significant condition*time interaction (p = 0.048), with early postmenopausal women demonstrating the most significant decline in FMD following IR. Conclusion: Our findings indicate that endothelial resistance to IR injury is attenuated in healthy early postmenopausal women

Short-term exercise-induced protection of cardiovascular function and health: why and how fast does the heart benefit from exercise?

Abstract: Regular exercise training has potent and powerful protective effects against the development of cardiovascular disease. These cardioprotective effects of regular exercise training are partly explained through the effects of exercise on traditional cardiovascular risk factors and improvement in cardiac and vascular health, which take several weeks to months to develop. This review focuses on the observation that single bouts of exercise may also possess an underrecognized, clinically useful form of immediate cardioprotection. Studies, performed in both animals and humans, demonstrate that single or short-term exercise-induced protection (SEP) attenuates the magnitude of cardiac and/or vascular damage in response to prolonged ischaemia and reperfusion injury. This review highlights preclinical evidence supporting the hypothesis that SEP activates multiple pathways to confer immediate protection against ischaemic events, reduce the severity of potentially lethal ischaemic myocardial injury, and therefore act as a physiological first line of defence against injury. Given the fact that the extent of SEP could be modulated by exercise-related and subject-related factors, it is important to recognize and consider these factors to optimize future clinical implications of SEP. This review also summarizes potential effector signalling pathways (i.e. communication between exercising muscles to vascular/cardiac tissue) and intracellular pathways (i.e. reducing tissue damage) that ultimately confer protection against cardiac and vascular injury. Finally, we discuss potential future directions for designing adequate human and animal studies that will support developing effective SEP strategies for the (multi-)diseased and aged individual

Impact of handgrip exercise and ischemic preconditioning on local and remote protection against endothelial reperfusion injury in young men.

Aims/Hypothesis: Ischemic preconditioning (IPC), cyclical bouts of non-lethal ischemia, provides immediate protection against ischemic injury, which is evident both locally and remotely. Given the similarities in protective effects of exercise with ischemic preconditioning, we examined whether handgrip exercise also offers protection against endothelial ischemia-reperfusion (IR)-injury, and whether this protection is equally present in the local (exercised) and remote (contralateral, non-exercised) arm. Methods: Fifteen healthy males (age 24±3 years; BMI 25±2 kg/m2) attended the laboratory on 3 occasions. Bilateral brachial artery flow-mediated dilation (FMD) was examined at rest and following a temporary IR-injury in the upper arm. Prior to the IR-injury, in the dominant (local) arm participants performed (randomised, counterbalanced); i. 4x5 minutes unilateral handgrip exercise (50% maximal voluntary contraction), ii. 4x5 minutes unilateral IPC (220 mmHg), or iii. 4x5 minutes rest (control). Data were analysed using repeated measures general linear models. Results: Allometrically scaled FMD declined after IR in the control condition (4.6 ± 1.3% to 2.2 ± 1.7%, P<0.001), as well as following handgrip exercise (4.6 ± 1.6% to 3.4 ± 1.9%, P=0.01), however was significantly attenuated with IPC (4.5 ± 1.4% to 3.8 ± 3.5%, P=0.14). There were no differences between the local and remote arm. Conclusion: Our findings reinforce the established protective effects of IPC in young, healthy males, and also highlight a novel strategy to protect against IR injury with handgrip exercise, which warrants further study

Single and 7-day handgrip and squat exercise prevents endothelial ischaemia-reperfusion injury in individuals with cardiovascular disease risk factors

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

Exercise-induced release of cardiac troponin is attenuated with repeated bouts of exercise: impact of cardiovascular disease and risk factors.

Background: Prolonged exercise can induce cardiac troponin release. Since single bouts of exercise may protect against cardiac injury, we explored the hypothesis that the magnitude of exercise-induced release of troponin attenuates upon successive days of exercise. We also examined whether effects of successive exercise bouts differ between healthy participants and individuals with cardiovascular risk factors (CVRF) and established cardiovascular disease (CVD). Methods: We examined cardiac troponin I (cTnI) concentrations in 383 participants (61±14 years) at rest and immediately following 4 consecutive days of long-distance walking (30-50 km/day). Participants were classified as either healthy (n=222), CVRF (n=75) or CVD (n=86). Results: Baseline cTnI concentrations were significantly higher in CVD and CVRF participants compared to healthy (P<0.001). Exercise-induced elevations in cTnI were observed in all groups following all days of walking compared to baseline (P<0.001). Tobit regression analysis on absolute cTnI concentrations revealed a significant day*group interaction (P=0.04). Following day 1 of walking, post-hoc analysis showed that exercise-induced elevations in cTnI attenuated on subsequent days in healthy and CVRF, but not in CVD. Odds ratios for incident cTnI concentrations above the upper reference limit were significantly higher in comparison to baseline on Day 1 for healthy (4.90 (95% CI 1.58-15.2)) and CVD participants (14.9 (1.86-125)); and remained significantly higher than baseline on all subsequent days in CVD. Conclusions: The magnitude of post-exercise cTnI concentrations following prolonged walking exercise significantly declines upon repeated days of exercise in healthy individuals and those with CVRF, whilst this decline is not present in CVD patients