Remote Ischemic Conditioning: Challenges and Opportunities

Remote ischemic conditioning (RIC) has been investigated as a promising, safe, and well-tolerated nonpharmacological therapy for cardio-cerebrovascular disease over the past 3 decades; variable results have been found when it is used in cerebrovascular versus cardiovascular disease. For patients with cardiovascular disease, milestone studies suggest that the roles of RIC may be limited. Recently, however, 2 large trials investigating RIC in patients with cerebrovascular disease found promising results, which may reignite the field’s research prospects after its setbacks in the cardiovascular field. This perspectives article highlights several important clinical trials of RIC in the cardio-cerebrovascular disease and describes the many challenges of RIC in clinical translation. Finally, based on the available evidence, several promising research directions such as chronic RIC, early initiation in target population, improvement of compliance, better understanding of dosing, and identification of specific biomarkers are proposed and should be investigated before RIC can become applied into clinical practice for patient benefit.

[1]  A. H. Moffitt August 2023 , 2023, American Journal of Orthodontics and Dentofacial Orthopedics.

[2]  D. Liebeskind,et al.  Chronic remote ischaemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis (the RICA trial): a multicentre, randomised, double-blind sham-controlled trial in China , 2022, The Lancet Neurology.

[3]  Ling Zhang,et al.  Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial. , 2022, JAMA.

[4]  X. Ji,et al.  Chronic remote ischemic conditioning for symptomatic internal carotid or middle cerebral artery occlusion: A prospective cohort study , 2022, CNS neuroscience & therapeutics.

[5]  I. Winship,et al.  Immune Modulation as a Key Mechanism for the Protective Effects of Remote Ischemic Conditioning After Stroke , 2021, Frontiers in Neurology.

[6]  Yuchuan Ding,et al.  Mini-review (Part II): A clinical consideration on exercise and ischemic conditioning in stroke rehabilitation , 2021, Brain circulation.

[7]  Hangil Lee,et al.  Timing is everything: Exercise therapy and remote ischemic conditioning for acute ischemic stroke patients , 2021, Brain circulation.

[8]  A. Saguner,et al.  Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke , 2020, Neurology.

[9]  Scott A. Prentice,et al.  Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial , 2019, Lancet.

[10]  J. Rossaint Propofol Anesthesia and Remote Ischemic Preconditioning: An Unfortunate Relationship. , 2018, Anesthesia and analgesia.

[11]  O. Ziff,et al.  Remote ischaemic conditioning reduces infarct size in animal in vivo models of ischaemia-reperfusion injury: a systematic review and meta-analysis , 2016, Cardiovascular research.

[12]  D. Yellon,et al.  Ischaemic conditioning and reperfusion injury , 2016, Nature Reviews Cardiology.

[13]  D. Hess,et al.  Remote ischaemic conditioning—a new paradigm of self-protection in the brain , 2015, Nature Reviews Neurology.

[14]  J. Pepper,et al.  Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. , 2015, The New England journal of medicine.

[15]  D. Hasenclever,et al.  A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery. , 2015, The New England journal of medicine.

[16]  Laurie J. Pencille,et al.  The Chest Pain Choice Decision Aid: A Randomized Trial , 2012, Circulation. Cardiovascular quality and outcomes.

[17]  C. Terkelsen,et al.  Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial , 2010, The Lancet.

[18]  J. Downey,et al.  Preconditioning the myocardium: from cellular physiology to clinical cardiology. , 2003, Physiological reviews.

[19]  R. Kloner,et al.  Regional Ischemic 'Preconditioning' Protects Remote Virgin Myocardium From Subsequent Sustained Coronary Occlusion , 1993, Circulation.

[20]  R. Jennings,et al.  Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. , 1986, Circulation.

[21]  Protective Effect of Time Spent Walking on Risk of Stroke Stroke: Highlights of Selected Articles , 2013 .