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Scott A Miller - One of the best experts on this subject based on the ideXlab platform.
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effects of remote ischemic Preconditioning in high risk patients undergoing cardiac surgery remote impact a randomized controlled trial
Canadian Medical Association Journal, 2016Co-Authors: Michael Walsh, Richard P Whitlock, Amit X Garg, Jeanfrancois Legare, Andra E Duncan, Robert Zimmerman, Scott A MillerAbstract:Background: Remote ischemic Preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. Methods: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic Preconditioning or a sham procedure after induction of anesthesia. The Preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase–myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. Results: We randomly assigned 128 patients to remote ischemic Preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] −0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI −0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic Preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). Interpretation: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. Trial registration: ClinicalTrials.gov, no. NCT01071265.
Jurgen Peters - One of the best experts on this subject based on the ideXlab platform.
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interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic Preconditioning during coronary artery bypass grafting
The Journal of Thoracic and Cardiovascular Surgery, 2014Co-Authors: Eva Kottenberg, Judith Musiolik, Matthias Thielmann, Heinz Jakob, Jurgen Peters, Gerd HeuschAbstract:Objective Remote ischemic Preconditioning protects the myocardium from ischemia/reperfusion injury. We recently identified protection by remote ischemic Preconditioning to be associated with the activation of signal transducer and activator of transcription 5 in left ventricular biopsy specimens of patients undergoing coronary artery bypass grafting during isoflurane anesthesia. Because remote ischemic Preconditioning did not protect the heart during propofol anesthesia, we hypothesized that propofol anesthesia interferes with signal transducer and activator of transcription 5 activation. Methods In a randomized, single-blind, placebo-controlled, prospective study, we analyzed an array of established cardioprotective proteins during propofol anesthesia with or without remote ischemic Preconditioning in 24 nondiabetic patients with 3-vessel coronary artery disease. Results Remote ischemic Preconditioning (n = 12) compared with no remote ischemic Preconditioning (n = 12) failed to decrease the area under the troponin I time curve (273 ± 184 ng/mL × 72 hours vs 365 ± 301 ng/mL × 72 hours; P = .374). Although phosphorylation of several protein kinases was increased from baseline to reperfusion, signal transducer and activator of transcription 5 phosphorylation was not increased and was not different between the remote ischemic Preconditioning and no remote ischemic Preconditioning groups. Conclusions Remote ischemic Preconditioning during propofol anesthesia did not evoke either signal transducer and activator of transcription 5 activation or cardioprotection, implying interaction of propofol with cardioprotective signaling upstream of signal transducer and activator of transcription 5.
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cardioprotective and prognostic effects of remote ischaemic Preconditioning in patients undergoing coronary artery bypass surgery a single centre randomised double blind controlled trial
The Lancet, 2013Co-Authors: Matthias Thielmann, Eva Kottenberg, Petra Kleinbongard, Daniel Wendt, Nilgun Gedik, Susanne Pasa, Vivien Price, Konstantinos Tsagakis, Markus Neuhauser, Jurgen PetersAbstract:Summary Background Remote ischaemic Preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We investigated the safety and efficacy of this procedure. Methods Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were prospectively randomised to receive remote ischaemic Preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia) or no ischaemic Preconditioning (control). The primary endpoint was myocardial injury, as reflected by the geometric mean area under the curve (AUC) for perioperative concentrations of cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was the main safety endpoint. Analysis was done in intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT01406678. Findings 329 patients were enrolled. Baseline characteristics and perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72 h (95% CI 237–298) in the remote ischaemic Preconditioning group and 321 ng/mL (287–360) in the control group. In the intention-to-treat population, the ratio of remote ischaemic Preconditioning to control for cTnI AUC was 0·83 (95% CI 0·70–0·97, p=0·022). cTnI release remained lower in the per-protocol analysis (0·79, 0·66–0·94, p=0·001). All-cause mortality was assessed over 1·54 (SD 1·22) years and was lower with remote ischaemic Preconditioning than without (ratio 0·27, 95% CI 0·08–0·98, p=0·046). Interpretation Remote ischaemic Preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery. Funding German Research Foundation.
Matthias Thielmann - One of the best experts on this subject based on the ideXlab platform.
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interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic Preconditioning during coronary artery bypass grafting
The Journal of Thoracic and Cardiovascular Surgery, 2014Co-Authors: Eva Kottenberg, Judith Musiolik, Matthias Thielmann, Heinz Jakob, Jurgen Peters, Gerd HeuschAbstract:Objective Remote ischemic Preconditioning protects the myocardium from ischemia/reperfusion injury. We recently identified protection by remote ischemic Preconditioning to be associated with the activation of signal transducer and activator of transcription 5 in left ventricular biopsy specimens of patients undergoing coronary artery bypass grafting during isoflurane anesthesia. Because remote ischemic Preconditioning did not protect the heart during propofol anesthesia, we hypothesized that propofol anesthesia interferes with signal transducer and activator of transcription 5 activation. Methods In a randomized, single-blind, placebo-controlled, prospective study, we analyzed an array of established cardioprotective proteins during propofol anesthesia with or without remote ischemic Preconditioning in 24 nondiabetic patients with 3-vessel coronary artery disease. Results Remote ischemic Preconditioning (n = 12) compared with no remote ischemic Preconditioning (n = 12) failed to decrease the area under the troponin I time curve (273 ± 184 ng/mL × 72 hours vs 365 ± 301 ng/mL × 72 hours; P = .374). Although phosphorylation of several protein kinases was increased from baseline to reperfusion, signal transducer and activator of transcription 5 phosphorylation was not increased and was not different between the remote ischemic Preconditioning and no remote ischemic Preconditioning groups. Conclusions Remote ischemic Preconditioning during propofol anesthesia did not evoke either signal transducer and activator of transcription 5 activation or cardioprotection, implying interaction of propofol with cardioprotective signaling upstream of signal transducer and activator of transcription 5.
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cardioprotective and prognostic effects of remote ischaemic Preconditioning in patients undergoing coronary artery bypass surgery a single centre randomised double blind controlled trial
The Lancet, 2013Co-Authors: Matthias Thielmann, Eva Kottenberg, Petra Kleinbongard, Daniel Wendt, Nilgun Gedik, Susanne Pasa, Vivien Price, Konstantinos Tsagakis, Markus Neuhauser, Jurgen PetersAbstract:Summary Background Remote ischaemic Preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We investigated the safety and efficacy of this procedure. Methods Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were prospectively randomised to receive remote ischaemic Preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia) or no ischaemic Preconditioning (control). The primary endpoint was myocardial injury, as reflected by the geometric mean area under the curve (AUC) for perioperative concentrations of cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was the main safety endpoint. Analysis was done in intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT01406678. Findings 329 patients were enrolled. Baseline characteristics and perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72 h (95% CI 237–298) in the remote ischaemic Preconditioning group and 321 ng/mL (287–360) in the control group. In the intention-to-treat population, the ratio of remote ischaemic Preconditioning to control for cTnI AUC was 0·83 (95% CI 0·70–0·97, p=0·022). cTnI release remained lower in the per-protocol analysis (0·79, 0·66–0·94, p=0·001). All-cause mortality was assessed over 1·54 (SD 1·22) years and was lower with remote ischaemic Preconditioning than without (ratio 0·27, 95% CI 0·08–0·98, p=0·046). Interpretation Remote ischaemic Preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery. Funding German Research Foundation.
Eva Kottenberg - One of the best experts on this subject based on the ideXlab platform.
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interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic Preconditioning during coronary artery bypass grafting
The Journal of Thoracic and Cardiovascular Surgery, 2014Co-Authors: Eva Kottenberg, Judith Musiolik, Matthias Thielmann, Heinz Jakob, Jurgen Peters, Gerd HeuschAbstract:Objective Remote ischemic Preconditioning protects the myocardium from ischemia/reperfusion injury. We recently identified protection by remote ischemic Preconditioning to be associated with the activation of signal transducer and activator of transcription 5 in left ventricular biopsy specimens of patients undergoing coronary artery bypass grafting during isoflurane anesthesia. Because remote ischemic Preconditioning did not protect the heart during propofol anesthesia, we hypothesized that propofol anesthesia interferes with signal transducer and activator of transcription 5 activation. Methods In a randomized, single-blind, placebo-controlled, prospective study, we analyzed an array of established cardioprotective proteins during propofol anesthesia with or without remote ischemic Preconditioning in 24 nondiabetic patients with 3-vessel coronary artery disease. Results Remote ischemic Preconditioning (n = 12) compared with no remote ischemic Preconditioning (n = 12) failed to decrease the area under the troponin I time curve (273 ± 184 ng/mL × 72 hours vs 365 ± 301 ng/mL × 72 hours; P = .374). Although phosphorylation of several protein kinases was increased from baseline to reperfusion, signal transducer and activator of transcription 5 phosphorylation was not increased and was not different between the remote ischemic Preconditioning and no remote ischemic Preconditioning groups. Conclusions Remote ischemic Preconditioning during propofol anesthesia did not evoke either signal transducer and activator of transcription 5 activation or cardioprotection, implying interaction of propofol with cardioprotective signaling upstream of signal transducer and activator of transcription 5.
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cardioprotective and prognostic effects of remote ischaemic Preconditioning in patients undergoing coronary artery bypass surgery a single centre randomised double blind controlled trial
The Lancet, 2013Co-Authors: Matthias Thielmann, Eva Kottenberg, Petra Kleinbongard, Daniel Wendt, Nilgun Gedik, Susanne Pasa, Vivien Price, Konstantinos Tsagakis, Markus Neuhauser, Jurgen PetersAbstract:Summary Background Remote ischaemic Preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We investigated the safety and efficacy of this procedure. Methods Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were prospectively randomised to receive remote ischaemic Preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia) or no ischaemic Preconditioning (control). The primary endpoint was myocardial injury, as reflected by the geometric mean area under the curve (AUC) for perioperative concentrations of cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was the main safety endpoint. Analysis was done in intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT01406678. Findings 329 patients were enrolled. Baseline characteristics and perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72 h (95% CI 237–298) in the remote ischaemic Preconditioning group and 321 ng/mL (287–360) in the control group. In the intention-to-treat population, the ratio of remote ischaemic Preconditioning to control for cTnI AUC was 0·83 (95% CI 0·70–0·97, p=0·022). cTnI release remained lower in the per-protocol analysis (0·79, 0·66–0·94, p=0·001). All-cause mortality was assessed over 1·54 (SD 1·22) years and was lower with remote ischaemic Preconditioning than without (ratio 0·27, 95% CI 0·08–0·98, p=0·046). Interpretation Remote ischaemic Preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery. Funding German Research Foundation.
DM Yellon - One of the best experts on this subject based on the ideXlab platform.
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Investigating the Signal Transduction Pathways Underlying Remote Ischemic Conditioning in the Porcine Heart
Cardiovascular Drugs and Therapy, 2012Co-Authors: D. J. Hausenloy, E. K. Iliodromitis, I. Andreadou, A. Papalois, G. Gritsopoulos, M. Anastasiou-nana, D. T. Kremastinos, DM YellonAbstract:Background The mechanism underlying remote ischemic conditioning (RIC) remains unclear. We investigated whether RIC protects the heart through the activation of the adenosine receptor and the PI3K-Akt pathway at the onset of myocardial reperfusion. Methods and results Domestic pigs (27–35 kg) were subjected to in situ left anterior descending coronary artery ischemia (60 min) followed by reperfusion (180 min) and randomised to the following: (1) Control- No additional intervention; (2) Remote ischemic Preconditioning (RIPC)- Four-5 min cycles of lower limb ischemia/reperfusion were administered prior to myocardial ischemia; (3) RIPC + Wort or 8-SPT: Wortmannin (Wort 20 μg/kg, a PI3K inhibitor) or 8-sulfophenyltheophylline (8-SPT 10 mg/kg, an adenosine receptor inhibitor) were administered intravenously 30 s before myocardial reperfusion to RIPC-treated animals; (4) Remote ischemic perconditioning (RIPerC)- Four-5 min cycles of lower limb ischemia/reperfusion were applied 1 min before myocardial reperfusion; (5) RIPerC + Wort or 8-SPT: Wort or 8-SPT were given 30 s before myocardial reperfusion to RIPerC-treated animals. Both RIPC and RIPerC reduced myocardial infarct size (13.3 ± 2.2% with RIPC, 18.2 ± 2.0% with RIPerC versus 48.8 ± 4.2% in control:P
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Effect of remote ischaemic Preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial
LANCET, 2007Co-Authors: DM YellonAbstract:Background Whether remote ischaemic Preconditioning, an intervention in which brief ischaemia of one tissue or organ protects remote organs from a sustained episode of ischaemia, is beneficial for patients undergoing coronary artery bypass graft surgery is unknown. We did a single-blinded randomised controlled study to establish whether remote ischaemic Preconditioning reduces myocardial injury in these patients.Methods 57 adult patients undergoing elective coronary artery bypass graft surgery were randomly assigned to either a remote ischaemic Preconditioning group (n=27) or to a control group (n=30) after induction of anaesthesia. Remote ischaemic Preconditioning consisted of three 5-min cycles of right upper limb ischaemia, induced by an automated cuff-inflator placed on the upper arm and inflated to 200 mmHg, with an intervening 5 min of reperfusion during which the cuff was deflated. Serum troponin-T concentration was measured before surgery and at 6, 12, 24, 48, and 72 h after surgery. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00397163.Findings Remote ischaemic Preconditioning significantly reduced overall serum troponin-T release at 6, 12, 24, and 48 h after surgery. The total area under the curve was reduced by 43%, from 36.12 mu g/L (SD 26.08) in the control group to 20.58 mu g/L (9.58) in the remote ischaemic Preconditioning group (mean difference 15.55 [SD 5.32]; 95% CI 4.88-26.21; p=0.005).Interpretation We have shown that adult patients undergoing elective coronary artery bypass graft surgery at a single tertiary Centre could benefit from remote ischaemic Preconditioning, using transient upper limb ischaemia.
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Survival kinases in ischemic Preconditioning and postconditioning
CARDIOVASC RES, 2006Co-Authors: DM YellonAbstract:Despite nearly twenty years of research into the field of ischemic Preconditioning, the actual mechanism of protection remains unclear. However, much progress has been made in elucidating the signal transduction pathways that convey the extracellular signal initiated by the Preconditioning stimulus to the intracellular targets of cardioprotection, with many of these pathways involving the activation of a diverse array of survival protein kinase cascades. The powerful protective benefits of ischemic Preconditioning have not yet been realised in the clinical arena, not least because of the prerequisite for any Preconditioning intervention to be applied prior to the onset of index ischemia, which in the case of an acute myocardial infarction is difficult to institute. In this regard, the newly described phenomenon of ischemic postconditioning, which comprises a cardioprotective intervention that can be applied at the time of myocardial reperfusion, offers a far more attractive and amenable approach to myocardial protection. Interestingly, certain survival protein kinase cascades recruited at the time of myocardial reperfusion appear to be shared by both ischemic Preconditioning and postconditioning, thereby offering a potentially common target of cardioprotection. The often disputed roles these different protein kinases play in mediating the cardioprotective effects of ischemic Preconditioning and postconditioning are reviewed in this article, and include protein kinases C, G, and A, members of the MAPK family (Erk1/2, p38, INK and BMK1), the PI3K-Akt cascade, and the JAK-STAT pathway. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
