Remote ischemic conditioning: a promising therapeutic intervention for multi-organ protection

Abstract

Despite decades of formidable exploration, multi-organ ischemia-reperfusion injury (IRI) encountered, particularly amongst elderly patients with clinical scenarios, such as age-related arteriosclerotic vascular disease, heart surgery and organ transplantation, is still an unsettled conundrum that besets clinicians. Remote ischemic conditioning (RIC), delivered via transient, repetitive noninvasive IR interventions to distant organs or tissues, is regarded as an innovative approach against IRI. Based on the available evidence, RIC holds the potential of affording protection to multiple organs or tissues, which include not only the heart and brain, but also others that are likely susceptible to IRI, such as the kidney, lung, liver and skin. Neuronal and humoral signaling pathways appear to play requisite roles in the mechanisms of RIC-related beneficial effects, and these pathways also display inseparable interactions with each other. So far, several hurdles lying ahead of clinical translation that remain to be settled, such as establishment of biomarkers, modification of RIC regimen, and deep understanding of underlying minutiae through which RIC exerts its powerful function. As this approach has garnered an increasing interest, herein, we aim to encapsulate an overview of the basic concept and postulated protective mechanisms of RIC, highlight the main findings from proof-of-concept clinical studies in various clinical scenarios, and also to discuss potential obstacles that remain to be conquered. More well designed and comprehensive experimental work or clinical trials are warranted in future research to confirm whether RIC could be utilized as a non-invasive, inexpensive and efficient adjunct therapeutic intervention method for multi-organ protection.

Remote ischemic conditioning for the treatment of ischemic moyamoya disease

“…Remote ischemic conditioning strategy has been suggested to treat both acute ischemic stroke and intracranial atherosclerosis (ICAS) . Our previous study indicated that RIC reduced the incidence of stroke recurrence in ICAS patients from 26.7% to 7.9% after 300 days continuous intervention .…”

“…Recently, remote ischemic conditioning (RIC) has garnered great attention due to its efficacious therapeutic benefit on atherosclerotic intracranial arterial stenosis (ICAS) . It has been demonstrated that RIC can increase the tolerance to cerebral ischemia, reduce stroke recurrence, improve cerebral perfusion, and promote compensatory collateral network formation .…”

“…It has been demonstrated that RIC can increase the tolerance to cerebral ischemia, reduce stroke recurrence, improve cerebral perfusion, and promote compensatory collateral network formation . Moreover, RIC is a noninvasive, easy‐to‐use, and low‐cost strategy in comparison with revascularization surgery . Herein, we hypothesized that RIC may yield a safe and effective treatment strategy to patients with ischemic MMD (iMMD), a modality that is hitherto undescribed for this disease entity.…”

The role of PAK1 in the sensitivity of kidney epithelial cells to ischemia-like conditions

“…Protection of at-risk population from acute kidney injury has attracted considerable attention, but the practical outcome to date has been rather limited. A possibility to pre-condition kidney to ischemia by transient ischemic treatment of remote organs is considered as a non-pharmacological measure [33]. However, clinical results for this technique vary considerably between studies [34][35][36], perhaps reflecting the need for further optimization of the procedure, as well as the differences in the study populations [37].…”

Intermittent hypoxia promotes functional neuroprotection from retinal ischemia in untreated first-generation offspring

“…To ensure rigor, we quantified postischemic retinal function by electroretinography in large cohorts. Repetitive systemic hypoxia, which has a human correlate in remote limb conditioning (25), served as the epigenetic conditioning stimulus. We also interrogated the intergenerational neuroprotective phenotype by quantitative mass spectrometry of retinae from F1 mice derived from conditioned and nonconditioned parents.…”