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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.

SUBMITTER: Che R

PROVIDER: S-EPMC6389851 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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rt-PA with remote ischemic postconditioning for acute ischemic stroke.

Che Ruiwen R Zhao Wenbo W Ma Qingfeng Q Jiang Fang F Wu Longfei L Yu Zhipeng Z Zhang Qian Q Dong Kai K Song Haiqing H Huang Xiaoqin X Ji Xunming X

Annals of clinical and translational neurology 20190116 2

<h4>Objective</h4>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).<h4>Methods</h4>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 repe ...[more]

PMID: 30847368

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Project description:Background Remote limb ischemic postconditioning (RLIPoC) has been demonstrated to protect against ischemic stroke. However, the underlying mechanisms of RLIPoC mediating cross-organ protection remain to be fully elucidated. Methods and Results Ischemic stroke was induced by middle cerebral artery occlusion for 60 minutes. RLIPoC was performed with 3 cycles of 10-minute ischemia followed by 10-minute reperfusion of the bilateral femoral arteries immediately after middle cerebral artery reperfusion. The percentage of regulatory T cells (Tregs) in the spleen, blood, and brain was detected using flow cytometry, and the number of Tregs in the ischemic hemisphere was counted using transgenic mice with an enhanced green fluorescent protein-tagged Foxp3. Furthermore, the metabolic status was monitored dynamically using a multispectral optical imaging system. The Tregs were conditionally depleted in the depletion of Treg transgenic mice after the injection of the diphtheria toxin. The inflammatory response and neuronal apoptosis were investigated using immunofluorescent staining. Infarct volume and neurological deficits were evaluated using magnetic resonance imaging and the modified neurological severity score, respectively. The results showed that RLIPoC substantially reduced infarct volume, improved neurological function, and significantly increased Tregs in the spleen, blood, and ischemic hemisphere after middle cerebral artery occlusion. RLIPoC was followed by subsequent alteration in metabolites, such as flavin adenine dinucleotide and nicotinamide adenine dinucleotide hydrate, both in RLIPoC-conducted local tissues and circulating blood. Furthermore, nicotinamide adenine dinucleotide hydrate can mimic RLIPoC in increasing Tregs. Conversely, the depletion of Tregs using depletion of Treg mice compromised the neuroprotective effects conferred by RLIPoC. Conclusions RLIPoC protects against ischemic brain injury, at least in part by activating and maintaining the Tregs through the nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide hydrate pathway.

Project description:ObjectiveTo evaluate the clinical efficacy of intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke.MethodsA total of 76 patients with acute ischemic stroke admitted to the Encephalopathy Dept. of Zhecheng Hospital of Traditional Chinese Medicine between February 2021 and June 2022 were recruited in this prospective trial (ClinicalTrials.gov, NCT03884410) and patients were randomized 1:1 to receive either aspirin plus clopidogrel (control group) or aspirin plus clopidogrel and rt-PA intravenous thrombolytic therapy (experimental group), with 38 cases in each group. The treatment efficiency, National Institute of Health stroke scale (NIHSS) scores, daily living ability, coagulation function, serum Lipoprotein-associated phospholipaseA2 (Lp-PLA2), homocysteine (HCY), hypersensitive C-reactive protein (hsCRP) levels, adverse events, and prognosis were evaluated and compared between the two groups.ResultsIntravenous thrombolysis with rt-PA resulted in a better treatment outcome of patients versus aspirin plus clopidogrel (P<0.05). Patients with rt-PA exhibited better improvement in neurological function than those with aspirin plus clopidogrel, as shown by the lower NIHSS scores (P<0.05). Intravenous thrombolysis with rt-PA resulted in a better quality of life of patients than aspirin plus clopidogrel, indicated by the higher Barthel Index (BI) levels (P<0.05). The lower von Willebrand factor (vWF) and Factor VIII (F) levels indicated better coagulation function of patients with rt-PA versus those with aspirin plus clopidogrel (P<0.05). The lower serum concentrations of Lp-PLA2, HCY, and hsCRP suggested patients with rt-PA had milder inflammatory responses versus those without rt-PA (P<0.05). There was no significant difference in the incidence of adverse events in the two groups (P>0.05). Intravenous thrombolytic therapy with rt-PA better enhanced the prognosis of patients than with aspirin plus clopidogrel (P<0.05).ConclusionCompared with conventional pharmacological regimens, additional rt-PA intravenous thrombolytic therapy improves the clinical outcome of patients with acute ischemic stroke, promotes neurological recovery, and enhances patient prognosis without increasing the risk of patient-related adverse events.

Project description:Rationale: Remote ischemic perconditioning during cerebral ischemia (RIPerC) refers to the application of brief episodes of transient limb ischemia commonly to a limb, it represents a new safe, simple and low-cost paradigm in neuroprotection. Aim and/or Hypothesis: To evaluate the effects of RIPerC on acute ischemic stroke (AIS) patients, applied in the ambulance, to improve functional outcomes compared with standard of care. Sample Size Estimates: A sample size of 286 patients in each arm achieves 80% power to detect treatment differences of 14% in the outcome, using a two-sided binomial test at significance level of 0.05, assuming that 40% of the control patients will experience good outcome and an initial misdiagnosis rate of 29%. Methods and Design: We aim to conduct a multicentre study of pre-hospital RIPerC application in AIS patients. A total of 572 adult patients diagnosed of suspected clinical stroke within 8 h of symptom onset and clinical deficit >0 according to prehospital rapid arterial occlusion evaluation (RACE) scale score will be randomized, in blocks of size 4, to RIPerC or sham. Patients will be stratified by RACE score scale. RIPerC will be started in the ambulance before hospital admission and continued in the hospital if necessary. It will consist of five cycles of electronic tourniquet inflation and deflation (5 min each). The cuff pressure for RIPerC will be 200 mmHg during inflation. Sham will only simulate vibration of the device. Study Outcome(s): The primary outcome will be the difference in the proportion of patients with good outcomes as defined by a mRS score of 2 or less at 90 days. Secondary outcomes to be monitored will include early neurological improvement rate, treatment related serious adverse event rates, size of the infarct volume, symptomatic intracranial hemorrhage, metabolomic and lipidomic response to RIPerC and Neuropsychological evaluation at 90 days. Discussion: Neuroprotective therapies could not only increase the benefits of available reperfusion therapies among AIS patients but also provide an option for patients who are not candidates for these treatments. REMOTE-CAT will investigate the clinical benefit of RIC as a new neuroprotective strategy in AIS. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03375762.

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Rt-PA with remote ischemic postconditioning for acute ischemic stroke.

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rt-PA with remote ischemic postconditioning for acute ischemic stroke.

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