Seven consecutive days of remote ischaemic preconditioning improves cutaneous vasodilatory capacity in young adults

Key points: Remote ischaemic preconditioning (RIPC), induced by brief bouts of ischaemia followed by reperfusion, confers vascular adaptations that protect against subsequent bouts of ischaemia; however, the effect of RIPC repeated over several days on the human microcirculation is unknown. Using skin as a model, microvascular function was assessed at a control and a NO-inhibited area of skin before 1 day after and 1 week after administering seven consecutive days of repeated RIPC on the contralateral arm. Maximal vasodilatation was increased by ∼20-50% following 7 days of repeated RIPC, and this response remained elevated 1 week after stopping RIPC; however, NO-mediated vasodilatation was not affected by the RIPC stimulus. These data indicate that repeated RIPC augments maximal vasodilatation, but the underlying mechanism for this improvement is largely independent of NO. This finding suggests a role for other endothelium-derived mediators and/or for endothelium-independent adaptations with repeated RIPC.

Abstract: Remote ischaemic preconditioning (RIPC), induced by intermittent periods of ischaemia followed by reperfusion, confers cardiovascular protection from subsequent ischaemic bouts. RIPC increases conduit and resistance vessel function; however, the effect of RIPC on the microvasculature remains unclear. Using human skin as a microvascular model, we hypothesized that cutaneous vasodilatory (VD) function elicited by localized heating would be increased following repeated RIPC. Ten participants (23 ± 1 years, 6 males, 4 females) performed RIPC for seven consecutive days. Each daily RIPC session consisted of 4 repetitions of 5 min of arm blood flow occlusion interspersed by 5 min reperfusion. Before, 1 day after and 1 week after the 7 days of RIPC, two microdialysis fibres were placed in ventral forearm skin for continuous infusion of Ringer solution or 20 mM l-NAME. Red blood cell flux was measured by laser Doppler flowmetry at each fibre site during local heating (T_loc = 39°C) and during maximal VD elicited by heating (T_loc = 43°C) and 28 mM sodium nitroprusside infusion. Data were normalized to cutaneous vascular conductance (flux/mmHg). Seven days of RIPC did not alter the nitric oxide (NO) contribution to the VD response to local heating (P > 0.05). However, the maximal VD was augmented (Pre: 2.5 ± 0.2, Post: 3.8 ± 0.5 flux/mmHg; P < 0.05) and remained elevated 1 week post RIPC (3.3 ± 0.4 flux/mmHg; P < 0.05). Repeated RIPC improves maximal VD but does not affect NO-mediated VD in the cutaneous microvasculature. This finding suggests that other factors may explain the vasodilatory adaptations that occur following repeated RIPC.