One session of remote ischemic preconditioning does not improve vascular function in acute normobaric and chronic hypobaric hypoxia

Abstract

What is the central question of this study? It is suggested that remote ischemic preconditioning (RIPC) might offer protection against ischaemia-reperfusion injuries, but the utility of RIPC in high-altitude settings remains unclear. What is the main finding and its importance? We found that RIPC offers no vascular protection relative to pulmonary artery pressure or peripheral endothelial function during acute, normobaric hypoxia and at high altitude in young, healthy adults. However, peripheral chemosensitivity was heightened 24 h after RIPC at high altitude. Application of repeated short-duration bouts of ischaemia to the limbs, termed remote ischemic preconditioning (RIPC), is a novel technique that might have protective effects on vascular function during hypoxic exposures. In separate parallel-design studies, at sea level (SL; n = 16) and after 8-12 days at high altitude (HA; n = 12; White Mountain, 3800 m), participants underwent either a sham protocol or one session of four bouts of 5 min of dual-thigh-cuff occlusion with 5 min recovery. Brachial artery flow-mediated dilatation (FMD; ultrasound), pulmonary artery systolic pressure (PASP; echocardiography) and internal carotid artery (ICA) flow (ultrasound) were measured at SL in normoxia and isocapnic hypoxia (end-tidal PO2 maintained at 50 mmHg) and during normal breathing at HA. The hypoxic ventilatory response (HVR) was measured at each location. All measures at SL and HA were obtained at baseline (BL) and at 1, 24 and 48 h post-RIPC or sham. At SL, RIPC produced no changes in FMD, PASP, ICA flow, end-tidal gases or HVR in normoxia or hypoxia. At HA, although HVR increased 24 h post-RIPC compared with BL [2.05 ± 1.4 versus 3.21 ± 1.2 l min (% arterial O saturation) , P < 0.01], there were no significant differences in FMD, PASP, ICA flow and resting end-tidal gases. Accordingly, a single session of RIPC is insufficient to evoke changes in peripheral, pulmonary and cerebral vascular function in healthy adults. Although chemosensitivity might increase after RIPC at HA, this did not confer any vascular changes. The utility of a single RIPC session seems unremarkable during acute and chronic hypoxia.

The impact of acute remote ischaemic preconditioning on cerebrovascular function

“…Finally, RIPC did not impact cerebrovascular reactivity to inhalation of 5% CO 2 compared to the sham condition. To our knowledge, there is only one directly relevant study that assessed RIPC and cerebrovascular function in humans (Rieger et al 2017). In this study the authors measured cerebral blood flow responses to acute and chronic hypoxia, and found no effect of RIPC compared to controls, findings consistent with the present study.…”

Ischemic preconditioning prevents impact of prolonged sitting on glucose tolerance and markers of cardiovascular health but not cerebrovascular responses

“…Although positive effects of IPC on peripheral blood vessels have been demonstrated (9), our results suggest that IPC does not affect ICA during prolonged sitting. In two very recent studies, IPC was also found not to alter cerebral blood flow when measured at the MCA during a short period of sitting (3) or at the ICA in the supine position (20). Our data, supported by these recent studies, therefore suggest that IPC unlikely alters blood flow in centrally located arteries, a finding that contrasts with peripheral arteries.…”

“…Repeated bouts of ischemia followed by reperfusion, known as ischemic preconditioning (IPC), seem to have a capacity to prevent or attenuate ischemia-induced vascular function in peripheral arteries (9). These protective effects of IPC may also be present in cerebral arteries (21), although some studies report mixed findings (3,20). Related to the metabolic pathway, a previous study in animals found that IPC alters AMP-activated protein kinase activity in the mitochondria, potentially contributing to improved regulation of glucose metabolism (17).…”

The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations

“…In contrast, 15 min of severe isocapnic hypoxia (end‐tidal partial pressure of O 2 = 45 mmHg; equivalent to ∼5000 m) did not reduce endothelial function in healthy adults (Rieger et al . ). The latter study suggests that 15 min of hypoxia exposure may not be enough to elicit a reduction in endothelial function.…”

“…Although the mechanism(s) responsible for the observed decline in shear stress during acute hypoxia remain unknown, these authors attributed it to heightened sympathetic vascular constraint (Weisbrod et al 2001). In contrast, 15 min of severe isocapnic hypoxia (end-tidal partial pressure of O 2 = 45 mmHg; equivalent to ß5000 m) did not reduce endothelial function in healthy adults (Rieger et al 2017). The latter study suggests that 15 min of hypoxia exposure may not be enough to elicit a reduction in endothelial function.…”