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No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

ABSTRACT: Remote ischemic preconditioning (RIPC) by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG). Activation of signal transducer and activator of transcription 5 (STAT5) in left ventricular (LV) myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy.CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation) or placebo (cuff deflated) before skin incision (n?=?10/10). Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline) and at early (5-10 min) reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p?=?0.002). Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5-12 (ATG5-12) complex, light chain 3 (LC3), parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2)-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion.Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p?=?0.02). STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (?2.7-fold versus baseline, p?0.05).Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion.

SUBMITTER: Gedik N

PROVIDER: S-EPMC4010496 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

Gedik Nilgün N Thielmann Matthias M Kottenberg Eva E Peters Jürgen J Jakob Heinz H Heusch Gerd G Kleinbongard Petra P

PloS one 20140505 5

<h4>Objective</h4>Remote ischemic preconditioning (RIPC) by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG). Activation of signal transducer and activator of transcription 5 (STAT5) in left ventricular (LV) myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefo ...[more]

PMID: 24797938

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Project description:ImportanceData are lacking on the outcomes of patients with severely reduced left ventricular ejection fraction (LVEF) who undergo revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).ObjectiveTo compare the long-term outcomes in patients undergoing revascularization by PCI or CABG.Design, setting, and participantsThis retrospective cohort study performed in Ontario, Canada, from October 1, 2008, and December 31, 2016, included data from Ontario residents between 40 and 84 years of age with LVEFs less than 35% and left anterior descending (LAD), left main, or multivessel coronary artery disease (with or without LAD involvement) who underwent PCI or CABG. Exclusion criteria were concomitant procedures, previous CABG, metastatic cancer, dialysis, CABG and PCI on the same day, and emergency revascularization within 24 hours of a myocardial infarction (MI). Data analysis was performed from June 2, 2018, to December 28, 2018.ExposuresRevascularization by PCI or CABG.Main outcomes and measuresThe primary outcome was all-cause mortality. Secondary outcomes were death from cardiovascular disease, major adverse cardiovascular events (MACE; defined as stroke, subsequent revascularization, and hospitalization for MI or heart failure), and each of the individual MACE.ResultsA total of 12 113 patients (mean [SD] age, 64.8 (11.0) years for the PCI group and 65.6 [9.7] years for the CABG group; 5084 (72.5%) male for the PCI group and 4229 (82.9%) male for the PCI group) were propensity score matched on 30 baseline characteristics: 2397 patients undergoing PCI and 2397 patients undergoing CABG. The median follow-up was 5.2 years (interquartile range, 5.0-5.3). Patients who received PCI had significantly higher rates of mortality (hazard ratio [HR], 1.6; 95% CI, 1.3-1.7), death from cardiovascular disease (HR 1.4, 95% CI, 1.1-1.6), MACE (HR, 2.0; 95% CI, 1.9-2.2), subsequent revascularization (HR, 3.7; 95% CI, 3.2-4.3), and hospitalization for MI (HR, 3.2; 95% CI, 2.6-3.8) and heart failure (HR, 1.5; 95% CI, 1.3-1.6) compared with matched patients who underwent CABG.Conclusions and relevanceIn this study, higher rates of mortality and MACE were seen in patients who received PCI compared with those who underwent CABG. The findings may provide insight to physicians who are involved in decision-making for these patients.

Project description:BackgroundNeurological complications after cardiac surgery have a profound impact on postoperative survival and quality of life. The increasing importance of strategies designed to improve neurological outcomes mirrors the growing risk burden of the contemporary cardiac surgical population. Remote ischemic preconditioning (RIPC) reduces adverse sequelae of ischemia in vulnerable organs by subjecting tissues with high ischemic tolerance to brief periods of hypoperfusion. This trial will evaluate the neuroprotective effect of RIPC in the cardiac surgical arena, by employing magnetic resonance imaging (MRI) and neurocognitive testing.MethodsPatients scheduled for elective coronary artery bypass grafting with the use of cardiopulmonary bypass will be screened for the study. Eligible patients will be randomized to undergo either a validated RIPC protocol or a sham procedure. The RIPC will be induced by inflation of a blood pressure cuff to 200 mmHg for 5 minutes, followed by a 5-minute reperfusion period. Three sequences of interchanging cuff inflations and deflations will be employed. Neurocognitive testing and MRI imaging will be performed preoperatively and on postoperative day 7. Paired pre- and postoperative neurocognitive and neuroimaging data will then be compared. The primary composite outcome measure will consist of new ischemic lesions on brain MRI, postprocedural impairment in brain connectivity on resting-state functional MRI (rs-fMRI), and significant new declines in neurocognitive performance. The secondary endpoint measures will be the individual components of the primary endpoint measures, expressed as continuous variables, troponin T release on postoperative day 1 and the incidence of major adverse cardiovascular events at 3 months postoperatively. Major adverse cardiovascular events, including accumulating cardiovascular mortality, stroke, nonfatal myocardial infarction, and rehospitalization for ischemia, will form a composite endpoint measure.DiscussionThis trial will aim to assess whether RIPC in patients subjected to surgical myocardial revascularization employing cardiopulmonary bypass initiates a neuroprotective response. Should the results of this trial indicate that RIPC is effective in reducing the incidence of adverse neurological events in patients undergoing coronary artery bypass grafting, it could impact on the current standard of care.Trial registrationClinicalTrials.gov NCT02177981.

Dataset Information

No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

Publications

No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

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