Delayed Cutaneous Microvascular Responses With Non-consecutive 3 Days of Remote Ischemic Preconditioning.

Jahyun Kim,James A Lang,Warren D Franke

doi:10.3389/fphys.2022.852966

Abstract

The optimal frequency and duration of remote ischemic preconditioning (RIPC) that augments microvascular function is unknown. A single bout of RIPC increases cutaneous endothelial function for ∼48 h, whereas 1 week of daily RIPC bouts improves more sustained endothelium-independent function. We hypothesized that 3 days of RIPC separated by rest days (3QOD RIPC) would result in sustained increases in both endothelium-dependent and endothelium-independent functions. Cutaneous microvascular function was assessed in 13 healthy young participants (aged 20.5 ± 3.9 years; 5 males, 8 females) before 3QOD and then 24, 48, and 72 h and a week after 3QOD. RIPC consisted of four repetitions of 5 min of blood flow occlusion separated by 5 min of reperfusion. Skin blood flow responses to local heating (Tloc = 42°C), acetylcholine (Ach), and sodium nitroprusside (SNP) were measured using laser speckle contrast imaging and expressed as cutaneous vascular conductance (CVC = PU⋅mmHg–1). Local heating-mediated vasodilation was increased 72 h after 3QOD and the increased responsivity persisted a week later (1.08 ± 0.24 vs. 1.34 ± 0.46, 1.21 ± 0.36 PU⋅mmHg–1; ΔCVC, pre-RIPC vs. 72 h, a week after 3QOD; P = 0.054). Ach-induced cutaneous vasodilation increased a week after 3QOD (0.73 ± 0.41 vs. 0.95 ± 0.49 PU⋅mmHg–1; ΔCVC, pre-RIPC vs. a week after 3QOD; P < 0.05). SNP-induced cutaneous vasodilation increased 24 h after 3QOD (0.47 ± 0.28 vs. 0.63 ± 0.35 PU⋅mmHg–1; ΔCVC, pre-RIPC vs. 24 h; P < 0.05), but this change did not persist thereafter. Thus, 3QOD induced sustained improvement in endothelium-dependent vasodilation but was not sufficient to sustain increases in endothelium-independent vasodilation.

Highlights

MATERIALS AND METHODSIschemic heart disease and stroke are leading causes of death and have a high recurrence rate (Briffa et al, 2011; Benjamin et al, 2019)
The local heating plateau and cutaneous vascular conductance (CVC) changed after 3QOD Remote ischemic preconditioning (RIPC)
Compared with a single bout of RIPC, as shown in our previous study (Kim et al, 2021), 3QOD elicits more sustained improvement in microvascular function. 3QOD RIPC induced delayed endothelium-dependent cutaneous vasodilation, and this improvement remained elevated for 1 week after the last RIPC bout

Summary

Introduction

MATERIALS AND METHODSIschemic heart disease and stroke are leading causes of death and have a high recurrence rate (Briffa et al, 2011; Benjamin et al, 2019). Regular moderate to high-intensity exercise training improves cardiovascular health and reduces cardiovascular disease incidence (Riebe et al, 2015). This intensity and frequency of exercise may not be practical in some clinical populations, such as those with severe ischemic heart disease or with limited mobility. Remote ischemic preconditioning (RIPC), consisting of three or four cycles of limb blood flow occlusion followed by reperfusion, may be an alternative intervention to improve cardiovascular function in these clinical populations. A single bout of RIPC transiently increases endothelial function that peaks ∼48 h after RIPC (Loukogeorgakis et al, 2005; Kim et al, 2021); this stimulus may not be sufficient to substantively improve clinical outcomes (Hausenloy et al, 2015; Meybohm et al, 2015)

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