Abstract
BackgroundRemote ischemic conditioning during cerebral ischemia (remote ischemic perconditioning, RIPerC) refers to the application of several cycles of brief ischemia and reperfusion (I/R) commonly to a limb, and it represents a new paradigm in neuroprotection with multiple mechanisms of action in ischemic stroke (IS) patients during acute phase. Some clinical trials just finished, and a few others are still ongoing; gather the current knowledge and pull it down to influence the present and future studies was the goal of this paper.MethodsA systematic review of published research papers and/or registered clinical trials since 2000 was performed.ResultsNineteen studies were identified and only four studies were completed. All of them have demonstrated that RIPerC is safe, feasible and well tolerated in IS patients. However, a high heterogeneity of clinical trial characteristics was observed: five (26.3%) randomized clinical trials (RCTs) included only thrombolytic-treated patients, three (15.8%) RCTs only thrombectomy-treated patients, and five (26.3%) RCTs required radiological confirmation of IS. Temporal inclusion criteria vary from 4 h to 48 h. Most of the clinical trials used 4 cycles of RIPerC in the upper non-affected limb. Interestingly, only three (16.7%) RCTs applied RIPerC during the transportation in the ambulance. Neuroimaging outputs were the main endpoints when endovascular therapy was applied; functional outcome is also the main endpoint in large-medium size studies.ConclusionsThis review summarizes the completed and ongoing clinical trials on RIPerC in IS patients, where RIPerC has been used alone or in combination with recanalization therapies. Ongoing clinical trials will provide new information on the best RIPerC intervention strategy and potentially improve the functional outcome of IS patients; definition of new RIPerC strategies would ideally aim at enhancing tissue preservation, promoting neurological recovery, and stratify patients to improve treatment feasibility.
Highlights
Remote ischemic conditioning during cerebral ischemia refers to the application of several cycles of brief ischemia and reperfusion (I/R) commonly to a limb, and it represents a new paradigm in neuroprotection with multiple mechanisms of action in ischemic stroke (IS) patients during acute phase
Among the 31 publications identified on Pubmed search, nine articles were not related to stroke (29%), four articles applied chronic PostRIC (13%), three articles were reviews of literature, three articles described design of the studies or protocols [14,15,16], two articles were on subarachnoid hemorrhage patients, one article was a sub-study and four articles were not eligible
After applying the inclusion criteria and the studies that accept inclusion beyond 48 h from the onset of symptoms were exclude; a total of 6 articles were included and analyzed in the systematic review [16,17,18,19,20,21], note that 4 out of the 6 papers were previously registered as clinical trials [18,19,20,21]
Summary
Remote ischemic conditioning during cerebral ischemia (remote ischemic perconditioning, RIPerC) refers to the application of several cycles of brief ischemia and reperfusion (I/R) commonly to a limb, and it represents a new paradigm in neuroprotection with multiple mechanisms of action in ischemic stroke (IS) patients during acute phase. The most common type of stroke is the ischemic stroke (IS), accounting for 87% of all strokes It is characterized by the occlusion within an arterial vessel supplying blood to an area of the brain, resulting in a corresponding loss of neurological function. It mainly occurs in elderly patients of both sexes with often multiple comorbidities (diabetes mellitus, hypertension, hyperlipidemia, obesity) [3]. There is a need for better and wider therapies to boost patient adherence
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