title: Can exercise mediate similar beneficial effects on endothelial function and endothelial reperfusion injury as ischemic preconditioning?
Creators: name: Bannell, D
Publisher: name: Liverpool John Moores University
Year: 2022

description: Abstract Introduction: The cardioprotective benefits of exercise are partly explained via long-term improvements in cardiovascular risk factors and/or physiological remodelling of (coronary) arteries. Nevertheless, work in animals revealed that a single bout of exercise offers immediate cardioprotection, similar to that of ischemic preconditioning (IPC). Whilst there is evidence that IPC (short repeated bouts of non-lethal ischemia followed by reperfusion) offers a biphasic pattern of protection and has both local (at site of injury) and remote effects (site distant to injury e.g. forearm), little is known about the cardioprotective properties of preconditioning from exercise in humans. To date, a small number of studies have investigated the immediate cardioprotective effects of exercise preconditioning in both animal and human models. In animals, 30 min of running exercise reduced infarct size immediately following exercise, with the protective effects lasting for up to 60 hours after the exercise (Yamashita et al., 1999) and the level of protection being more persistent when more than one bout was performed (Hoshida et al., 2002). Similarly, in the limited number of human studies performed, it has been demonstrated that a single bout of lower limb exercise is able to provide protection against endothelial ischemia reperfusion (IR)-injury (Seeger et al., 2015). However, more research is warranted to further explore the potential of (single bouts of) exercise as a form of preconditioning and to determine the most effective way to employ it. The overall aim of this study was to compare exercise preconditioning with IPC on the ability to provide immediate and clinically relevant protection against endothelial IR-injury in healthy individuals, and whether this protection was present in both the local and remote stimulus. Also, given that ageing negates the impact of IPC on endothelial IR injury (Loukogeorgakis et al., 2005) another aim was to examine whether exercise (squatting) preconditioning was 3 similarly attenuated with age. Methods: Fifteen healthy individuals (23.9 ± 3.1 yrs; BMI 25 ± 2 kg.m2) attended the laboratory on four separate occasions. Assessment of forearm maximal voluntary contraction was followed by three visits for each experimental condition: control, handgrip exercise and IPC. During each experimental visit, bilateral brachial artery flow-mediated dilation (FMD) was assessed at rest (baseline). Participants then either rested in the supine position for 40 min (Control), performed handgrip exercise (4 x 5 min of unilateral handgrip exercise, separated by 5 min rest) or were administered IPC (4 x 5 min upper-arm cuff inflation separated by 5 min reperfusion) followed by a 15-minute upper-arm occlusion (220 mm Hg) with 15-minute reperfusion to induce a temporary endothelial IR stimulus, followed by FMD assessment (post IR). A separate sub-study was conducted, to further explore whether the remote effects of preconditioning are also present when the preconditioning stimulus is applied to the lower limbs, but also whether preconditioning effects are present in older subjects. For this purpose, 12 young (23.5 ± 8.0 yrs; BMI 25 ± 3 kg.m2) and six elderly individuals (61.5 ± 5.2 yrs; BMI 25 ± 4 kg.m2) attended the laboratory for 3 experimental preconditioning visits (control, squats exercise and leg IPC). During each visit unilateral brachial FMD were assessed and IR stimulus was administered at the same time points as the handgrip study. Participants either rested in the supine position for 40 min (Control), performed squats exercise (4 x 5 min of body weight squats, separated by 5 min rest) or were administered leg IPC (4 x 5 min bilateral thigh cuff inflation separated by 5 min reperfusion). Results: In the handgrip study, in the local arm (i.e. the arm performing exercise and IPC) there was a trend for a condition*time interaction (P = 0.08). The reduction in FMD post IR-injury was less in handgrip exercise (0.5 % [1.7, 0.6]) and IPC (0.3 % [1.6, 1.0]) compared to control (1.8 % [2.4, 1.2]). In the remote arm (i.e. 4 the arm not performing exercise and IPC) there was a main effect of condition with FMD being 1.0 % (1.6, 0.4) lower in the control condition compared with handgrip exercise (P &lt; 0.01) and 1.1 % (1.9, 0.3) lower in the control condition compared with IPC (P = 0.01). In the squats study, in the young group there was a main effect of condition with FMD being 0.9 % (1.9, 0.0) lower in the control condition compared with leg IPC (P = 0.05). FMD was also lower in the squats condition by 1.1 % (1.9, 0.3) compared with leg IPC (P = 0.02). In the elderly group, there was a trend for a condition*time interaction (P = 0.09), the reduction in FMD was less following both exercise (0.6 % [2.1, 0.9]) and ischemic preconditioning (1.7 % [4.2, 0.7]) compared to control (3.0 % [4.6, 1.4]). Conclusion: This study suggests exercise preconditioning may offer both local and remote protection against endothelial IR-injury in young, healthy individuals in a similar capacity to traditional IPC and possibly to a greater extent in older individuals.