# Remote ischemic conditioning in intensive care: From bench to bedside

**Authors:** Sarah Benghanem, Laure Stiel, Youenn Jouan, Meryl Vedrenne-Cloquet, Yael Levy, Thomas Maldiney, Benjamine Sarton, Hatem Kallel, Nicolas Bréchot, Jérémie Joffre, Romain Gallet, Alexandre Gaudet, Louis Kreitmann

PMC · DOI: 10.1016/j.aicoj.2025.100018 · Annals of Intensive Care · 2026-01-16

## TL;DR

This review explores remote ischemic conditioning, a non-invasive technique to reduce tissue damage from blood flow disruption, and its potential in critical care settings.

## Contribution

The paper provides a comprehensive review of RIC's mechanisms, clinical applications, and ongoing research to improve its effectiveness in intensive care.

## Key findings

- RIC involves controlled ischemia in a distant organ to protect against I/R injury.
- Preclinical studies show RIC's efficacy, but clinical trials have mixed results.
- Ongoing research focuses on optimizing RIC delivery and identifying suitable patient groups.

## Abstract

Ischemia/reperfusion (I/R) injury is a pathological phenomenon involving temporary blood flow restriction (ischemia) followed by a period of reperfusion. This sudden variation induces oxidative stress, inflammation, and mitochondrial dysfunction, leading to severe cellular damage. I/R is a primary driver of organ injury in critically ill patients, particularly in conditions such as myocardial infarction, stroke, cardiac arrest, trauma, cardiac surgery, and various shock states.

Remote ischemic conditioning (RIC), a non-invasive strategy involving repeated controlled episodes of ischemia and reperfusion to a distant organ (typically a limb), has emerged as a potential strategy to attenuate I/R injury through systemic protective mechanisms. RIC can be applied at various time points: i) before ischemia (pre-conditioning); ii) during ischemia (per-conditioning); iii) after reperfusion has started (post-conditioning). While preclinical models have consistently demonstrated its efficacy, clinical trials to date have shown mixed results, with limited impact on key clinical outcomes.

In this narrative review, we first provide a brief historical overview and outline the molecular and cellular mechanisms underlying RIC. Second, we examine current evidence from both animal studies and human trials on the effect of RIC across several conditions such as myocardial infarction, stroke, cardiac arrest, trauma, cardiac surgery and shock. Finally, we discuss ongoing research efforts aimed at optimizing its delivery and identifying patient populations most likely to benefit from its use.

## Linked entities

- **Diseases:** myocardial infarction (MONDO:0005068), stroke (MONDO:0005098), cardiac arrest (MONDO:0000745), trauma (MONDO:0021178)

## Full-text entities

- **Genes:** IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, FXYD5 (FXYD domain containing ion transport regulator 5) [NCBI Gene 53827] {aka DYSAD, HSPC113, IWU1, KCT1, OIT2, PRO6241}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, MAP2K1 (mitogen-activated protein kinase kinase 1) [NCBI Gene 5604] {aka CFC3, MAPKK1, MEK1, MEL, MKK1, PRKMK1}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, MPO (myeloperoxidase) [NCBI Gene 4353], NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, KNG1 (kininogen 1) [NCBI Gene 3827] {aka BDK, BK, HAE6, HK, HMWK, KNG}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}
- **Diseases:** vasospasm (MESH:D020301), AIS (MESH:D000083242), hypotension (MESH:D007022), Ischemia (MESH:D007511), AKI (MESH:D058186), Stroke (MESH:D020521), myocardial injury (MESH:D009202), hemorrhagic (MESH:D006470), organ dysfunction (MESH:D009102), ST-Segment Elevation Myocardial Infarction (MESH:D000072657), glial and neuronal injury (MESH:D016472), cerebral edema (MESH:D001929), hemorrhagic stroke (MESH:D000083302), swelling (MESH:D004487), traumatic brain injury (MESH:D000070642), CA (MESH:D006323), brain infarction (MESH:D020520), cerebral hypoxic ischemia (MESH:D002545), cardiogenic shock (MESH:D012770), multiorgan failure (MESH:D051437), mitochondrial dysfunction (MESH:D028361), pain (MESH:D010146), critically ill (MESH:D016638), calcium overload (MESH:D019190), CONDITIONING (MESH:D020763), inflammation (MESH:D007249), OHCA (MESH:D058687), glial injury (MESH:D004194), injury (MESH:D014947), Shock (MESH:D012769), Sepsis (MESH:D018805), neurological sequelae (MESH:D009422), HIBI (MESH:D020925), septic (MESH:D001170), ventricular fibrillation (MESH:D014693), septic shock (MESH:D012772), cardiac (MESH:D006331), paresthesia (MESH:D010292), liver damage (MESH:D056486), heart failure (MESH:D006333), infarct (MESH:D007238), petechiae (MESH:D011693), ischemic attacks (MESH:D002546), LAD occlusion (MESH:D000094629), neuronal injury (MESH:D009410), coronary occlusion (MESH:D054059), metabolic acidosis (MESH:D000138), Hemorrhagic shock (MESH:D012771), cardiac and cerebrovascular (MESH:D002561), venous thrombosis (MESH:D020246), cerebral infarct (MESH:D002544), end-organ damage (MESH:C564816), RIC (MESH:D017202), artery (MESH:D012078), MACCE (MESH:D002318), acute myocardial infarction (MESH:D009203), subarachnoid hemorrhage (MESH:D013345), nerve injury (MESH:D000080902), intracerebral hemorrhage (MESH:D002543), cardiac death (MESH:D003643)
- **Chemicals:** NO (MESH:D009569), propofol (MESH:D015742), O2 (MESH:D010100), adenosine (MESH:D000241), ROS (MESH:D017382), LPS (MESH:D008070), ATP (MESH:D000255), urea (MESH:D014508), Cardiovasc Drugs (-)
- **Species:** Sus scrofa (pig, species) [taxon 9823], Ovis aries (domestic sheep, species) [taxon 9940], Canis lupus familiaris (dog, subspecies) [taxon 9615], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12934419/full.md

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12934419/full.md

## References

103 references — full list in the complete paper: https://tomesphere.com/paper/PMC12934419/full.md

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Source: https://tomesphere.com/paper/PMC12934419