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Long-term outcome following remote ischemic postconditioning during percutaneous coronary interventions-the RIP-PCI trial long-term follow-up.

ABSTRACT: The clinical value of ischemic conditioning during percutaneous coronary intervention (PCI) and mode of administration is controversial. Our aim was to assess the long-term effect of remote ischemic postconditioning among patients undergoing PCI. We randomized 360 patients undergoing PCI who presented with a negative troponin T at baseline into 3 groups: 2 groups received remote ischemic postconditioning (with ischemia applied to the arm in 1 group and to the thigh in the other group), and the third group acted as a control group. Remote ischemic postconditioning was applied during PCI immediately following stent deployment, by 3, 5-minute cycles of blood pressure cuff inflation to >200 mm Hg on the arm or thigh (20 mm Hg to the arm in the control), with 5-minute breaks between each cycle. There were no differences in baseline characteristics among the 3 groups. Periprocedural myocardial injury occurred in 33% (P = 0.64). After 1 year, there was no difference between groups in death (P = 0.91), myocardial infarction (P = 0.78), or repeat revascularization (P = 0.86). During 3 years of follow-up, there was no difference in death, myocardial infarction, and revascularization among the groups (P = 0.45). Remote ischemic postconditioning during PCI did not affect long-term cardiovascular outcome. A similar effect was obtained when remote ischemia was induced to the upper or lower limb. ClinicalTrials.gov Identifier: NCT00970827.

SUBMITTER: Lavi S

PROVIDER: S-EPMC6490325 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Long-term outcome following remote ischemic postconditioning during percutaneous coronary interventions-the RIP-PCI trial long-term follow-up.

Lavi Shahar S Abu-Romeh Nour N Wall Sabrina S Alemayehu Mistre M Lavi Ronit R

Clinical cardiology 20170111 5

The clinical value of ischemic conditioning during percutaneous coronary intervention (PCI) and mode of administration is controversial. Our aim was to assess the long-term effect of remote ischemic postconditioning among patients undergoing PCI. We randomized 360 patients undergoing PCI who presented with a negative troponin T at baseline into 3 groups: 2 groups received remote ischemic postconditioning (with ischemia applied to the arm in 1 group and to the thigh in the other group), and the t ...[more]

PMID: 28075499

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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:Percutaneous coronary intervention (PCI) relieves angina in patients with stable ischemic heart disease, but clinical trials have not shown that it improves survival. Between June 1999 and January 2004, we randomly assigned 2287 patients with stable ischemic heart disease to an initial management strategy of optimal medical therapy alone (medical-therapy group) or optimal medical therapy plus PCI (PCI group) and did not find a significant difference in the rate of survival during a median follow-up of 4.6 years. We now report the rate of survival among the patients who were followed for up to 15 years.We obtained permission from the patients at the Department of Veterans Affairs (VA) sites and some non-VA sites in the United States to use their Social Security numbers to track their survival after the original trial period ended. We searched the VA national Corporate Data Warehouse and the National Death Index for survival information and the dates of death from any cause. We calculated survival according to the Kaplan-Meier method and used a Cox proportional-hazards model to adjust for significant between-group differences in baseline characteristics.Extended survival information was available for 1211 patients (53% of the original population). The median duration of follow-up for all patients was 6.2 years (range, 0 to 15); the median duration of follow-up for patients at the sites that permitted survival tracking was 11.9 years (range, 0 to 15). A total of 561 deaths (180 during the follow-up period in the original trial and 381 during the extended follow-up period) occurred: 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (adjusted hazard ratio, 1.03; 95% confidence interval, 0.83 to 1.21; P=0.76).During an extended-follow-up of up to 15 years, we did not find a difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone in patients with stable ischemic heart disease. (Funded by the VA Cooperative Studies Program and others; COURAGE ClinicalTrials.gov number, NCT00007657.).

Project description:During acute reperfusion, the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes. However, whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear. In this study, RNA isolation and library preparation was performed for long noncoding RNA sequencing, followed by determining the coding potential of identified long noncoding RNAs and target gene prediction. Differential expression analysis, long noncoding RNA functional enrichment analysis, and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats. Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery. Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke. The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke. The predicted target genes of some of the identified long noncoding RNAs (cis targets) were related to the cellular response to ischemia and stress, cytokine signal transduction, inflammation, and apoptosis signal transduction pathways. In addition, 15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning. Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis. Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction. These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke. The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University (approval No. KMMU2018018) in January 2018.

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Long-term outcome following remote ischemic postconditioning during percutaneous coronary interventions-the RIP-PCI trial long-term follow-up.

Publications

Long-term outcome following remote ischemic postconditioning during percutaneous coronary interventions-the RIP-PCI trial long-term follow-up.

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