rt‐PA with remote ischemic postconditioning for acute ischemic stroke

Abstract

Objective To investigate the feasibility and safety of remote ischemic postconditioning ( RIPC ) in acute ischemic stroke patients after intravenous recombinant tissue plasminogen activator (rt‐ PA ) thrombolysis ( IVT ). Methods We performed a pilot randomized trial involving acute ischemic stroke patients with IVT . The patients were randomized 1:1 to receive RIPC or standard medical therapy. In the RIPC group, the participants underwent instant RIPC within 2 h of IVT , followed by repeated RIPC therapy for 7 days. The feasibility end point was the completion of RIPC and time from the first RIPC to finishing IVT in the RIPC group. The safety end point included tissue and neurovascular injury resulting from RIPC , changes in vital signs, level of plasma myoglobin, any hemorrhagic transformation, and other adverse events. Results Thirty patients (15 RIPC and 15 Control) were recruited after IVT . The mean age was 65.7 ± 10.2 years, with a National Institutes of Health Stroke Scale ( NIHSS ) score of 6.5 (4.0–10.0). The completion rate for RIPC was 97.0%. The mean time from first RIPC to completing IVT was 66.0 (25.0–75.0) min in the RIPC group. One case of hemorrhagic transformation was observed in the RIPC group. No significant difference was found in the level of myoglobin between the two groups ( P > 0.05). Interpretation RIPC is effective and safe for AIS patients after intravenous rt‐ PA thrombolysis.

Induced neuroprotection by remote ischemic perconditioning as a new paradigm in ischemic stroke at the acute phase, a systematic review

“…Among the 31 publications identi ed 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 (acute ischemic stroke-AIS patients and application of remote ischemic perconditioning-RIPerC) and the studies that accept inclusion beyond 48 hours 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). Twenty-seven randomized clinical trials (RCTs) were identi ed on clinicaltrials.gov.…”

“…Of these RCTs, 6 (22.2%) applied PostRIC and 4 (14.8%%) were not considered after inclusion/exclusion criteria were applied. 17 RCTs were further considered in the present systematic review (NCT0097596 (21), RESCUE-BRAIN (15,22), REVISE-1 (18), rtPA-RIC1 (19),…”

“…However, there were no signi cant differences in clinical neurological outcome between mRIC and control groups. The paper of Che et al (19), included only 30 patients treated with recombinant tissue plasminogen activator (rt-PA). Zhao et al (18) demonstrated that RIC is safe in 20 patients who underwent mechanical thrombectomy.…”

“…Furthermore, RIC was associated with changes of plasma biomarkers related to ischemic tolerance (IT) phenomena, such as HSP27 and phosphorylated HSP27, whose expression was signi cantly different when both arms (control vs. experimental) of the trial were compared (n=13) (17). These four publications included a limited and small number of recruited subjects (17)(18)(19)21). In contrast with previous studies, the multicenter RESCUE-BRAIN trial (20) was not only focused on IS patients who received or were candidate for revascularization therapies.…”

RIPC provides neuroprotection against ischemic stroke by suppressing apoptosis via the mitochondrial pathway

“…Previous studies have shown that RIC can reduce myocardial infarct size in patients with ST-elevation myocardial infarction treated by thrombolysis and that it can increase myocardial salvage in patients with acute myocardial infarction 29,30 . Accumulating evidence has revealed that RIC also plays a protective role in brains subjected to ischemia [31][32][33][34][35][36] . RIC can be divided into three types according to the onset time: (1) RIPC, in which RIC starts before the onset of brain ischemia; (2) RIPerC, in which RIC starts after the onset of ischemia and before reperfusion of the brain; and (3) RIPostC, in which RIC starts during the reperfusion period 12 .…”