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Derek J Hausenloy - One of the best experts on this subject based on the ideXlab platform.
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remote Ischemic Preconditioning and outcomes of cardiac surgery
The New England Journal of Medicine, 2015Co-Authors: Derek J Hausenloy, Luciano Candilio, Richard Evans, Cono Ariti, David P Jenkins, Shyam Kolvekar, Rosemary Knight, Gudrun Kunst, Chris Laing, Jennifer M NicholasAbstract:BACKGROUND: Whether remote Ischemic Preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. METHODS: We conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote Ischemic Preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. RESULTS: We enrolled a total of 1612 patients (811 in the control group and 801 in the Ischemic-Preconditioning group) at 30 cardiac surgery centers in the United Kingdom. There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote Ischemic Preconditioning group and those in the control group (212 patients [26.5%] and 225 patients [27.7%], respectively; hazard ratio with Ischemic Preconditioning, 0.95; 95% confidence interval, 0.79 to 1.15; P=0.58). Furthermore, there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury (assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery), acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life. CONCLUSIONS: Remote Ischemic Preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery. (Funded by the Efficacy and Mechanism Evaluation Program [a Medical Research Council and National Institute of Health Research partnership] and the British Heart Foundation; ERICCA ClinicalTrials.gov number, NCT01247545.).
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remote Ischemic Preconditioning and outcomes of cardiac surgery
The New England Journal of Medicine, 2015Co-Authors: Derek J Hausenloy, Luciano Candilio, Richard Evans, Cono Ariti, David P Jenkins, Shyam Kolvekar, Rosemary Knight, Gudrun Kunst, Chris Laing, Jennifer M NicholasAbstract:BackgroundWhether remote Ischemic Preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. MethodsWe conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote Ischemic Preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. ResultsWe enrolled a total of 1612 patients (811 in the control ...
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survival kinases in Ischemic Preconditioning and postconditioning
Cardiovascular Research, 2006Co-Authors: Derek J Hausenloy, Derek M 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, JNK and BMK1), the PI3K-Akt cascade, and the JAK-STAT pathway.
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Realizing the clinical potential of Ischemic Preconditioning and postconditioning.
Nature Clinical Practice Cardiovascular Medicine, 2005Co-Authors: Derek M Yellon, Derek J HausenloyAbstract:Various cardioprotective effects seen with Ischemic Preconditioning and postconditioning have been documented. The application of these methods in clinical practice is not, however, straightforward because of issues with timing and the need for further elucidation of mechanisms. This review discusses whether implementation in clinical practice is feasible. After an acute myocardial infarction (AMI), early reperfusion by thrombolysis or primary percutaneous coronary intervention remains the most-effective strategy for limiting the size of an evolving infarct. The mortality from AMI, however, remains significant, due partly to the lethal reperfusion injury that occurs on reperfusing the Ischemic myocardium. Novel cardioprotective strategies are required to target this form of injury. In Ischemic Preconditioning transient, nonlethal episodes of myocardial ischemia and reperfusion before the index Ischemic episode reduce infarct size. The cardioprotective potential of Ischemic Preconditioning has not been realized in clinical practice because it necessitates an intervention applied before the onset of AMI, which is difficult to predict. A more-amenable approach to cardioprotection is to intervene at the onset of reperfusion, the timing of which is under the control of the operator. In this regard, Ischemic postconditioning, in which transient episodes of myocardial ischemia and reperfusion administered at the onset of reperfusion reduce infarct size, constitutes one such intervention. Interestingly, studies suggest that Ischemic Preconditioning and postconditioning activate the same signaling pathway at the time of reperfusion, thereby offering a common target for cardioprotection. Therefore, the pharmacologic recruitment of this signaling pathway at the time of myocardial reperfusion might allow one to harness the cardioprotective potential of Ischemic Preconditioning and postconditioning. In this review, we discuss the potential application of Ischemic Preconditioning and postconditioning in the clinical arena of myocardial ischemia and reperfusion, and examine the common signaling pathways by which this might be achieved.
Jennifer M Nicholas - One of the best experts on this subject based on the ideXlab platform.
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remote Ischemic Preconditioning and outcomes of cardiac surgery
The New England Journal of Medicine, 2015Co-Authors: Derek J Hausenloy, Luciano Candilio, Richard Evans, Cono Ariti, David P Jenkins, Shyam Kolvekar, Rosemary Knight, Gudrun Kunst, Chris Laing, Jennifer M NicholasAbstract:BACKGROUND: Whether remote Ischemic Preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. METHODS: We conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote Ischemic Preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. RESULTS: We enrolled a total of 1612 patients (811 in the control group and 801 in the Ischemic-Preconditioning group) at 30 cardiac surgery centers in the United Kingdom. There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote Ischemic Preconditioning group and those in the control group (212 patients [26.5%] and 225 patients [27.7%], respectively; hazard ratio with Ischemic Preconditioning, 0.95; 95% confidence interval, 0.79 to 1.15; P=0.58). Furthermore, there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury (assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery), acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life. CONCLUSIONS: Remote Ischemic Preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery. (Funded by the Efficacy and Mechanism Evaluation Program [a Medical Research Council and National Institute of Health Research partnership] and the British Heart Foundation; ERICCA ClinicalTrials.gov number, NCT01247545.).
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remote Ischemic Preconditioning and outcomes of cardiac surgery
The New England Journal of Medicine, 2015Co-Authors: Derek J Hausenloy, Luciano Candilio, Richard Evans, Cono Ariti, David P Jenkins, Shyam Kolvekar, Rosemary Knight, Gudrun Kunst, Chris Laing, Jennifer M NicholasAbstract:BackgroundWhether remote Ischemic Preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. MethodsWe conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote Ischemic Preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. ResultsWe enrolled a total of 1612 patients (811 in the control ...
Rex C Bentley - One of the best experts on this subject based on the ideXlab platform.
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protective effects of Ischemic Preconditioning for liver resection performed under inflow occlusion in humans
Annals of Surgery, 2000Co-Authors: Pierre-alain Clavien, Surinder S Yadav, David Sindram, Rex C BentleyAbstract:Clamping of the portal triad (inflow occlusion), also called the Pringle maneuver, is often used during liver surgery to minimize blood loss. Excessive blood loss during surgery and the need for transfusion have been shown to hinder the postoperative course. 1–3 Several recent clinical 4–6 and experimental 7,8 studies have demonstrated that intermittent clamping of the portal triad is better tolerated than prolonged continuous periods of ischemia. 5,6 However, the beneficial effect of intermittent clamping on Ischemic injury, as assessed by postoperative serum transaminase and bilirubin levels, is counterbalanced by increased blood loss during the various reperfusion periods. If the protective mechanisms of intermittent ischemia could be identified, then innovative strategies could be developed to protect the liver against Ischemic and reperfusion injury without increased blood loss. One strategy that could be applicable to hepatic surgery is Ischemic Preconditioning. Ischemic Preconditioning is a short period of ischemia followed by a brief period of reperfusion before a sustained Ischemic insult. Most of the data on Ischemic Preconditioning have been gathered in the heart, with a focus on the ability of Preconditioning to reduce the size of a myocardial infarction. A few of the involved extracellular mediators, such as adenosine 9 and nitric oxide, 10 have been identified. Protection by Ischemic Preconditioning has been subsequently documented in a variety of tissues, including skeletal muscle, 11 brain, 12 spinal cord, 13 retina, 14 and intestine, 15 and is thought to be part of a ubiquitous protective mechanism against repetitive stress on cells and cell systems. Only a few investigators have studied the effects of Ischemic Preconditioning in the liver, 16–21 and only data in rodents are available. These studies have suggested that the liver could also be protected against Ischemic insults by Preconditioning. We recently identified an Ischemic Preconditioning protocol (10 minutes of ischemia followed by 15 minutes of reperfusion) that completely prevented animal death in mice subjected to 75 minutes of total hepatic ischemia, a lethal condition without Preconditioning. 16 In view of our previous findings that apoptosis of sinusoidal endothelial cells and hepatocytes is a prominent feature of reperfusion injury in the warm Ischemic liver, 22 we also studied the effects of Ischemic Preconditioning on postreperfusion apoptosis in a mouse model of partial hepatic ischemia. 16 Ischemic Preconditioning was associated with complete abrogation of the massive hepatocellular apoptosis seen after prolonged periods of ischemia and downregulation of cytoplasmic caspase activities. Caspases are a family of cysteine proteases initiating complex proteolytic reactions leading to cell disassembly and death. 23 The beneficial effects of intermittent clamping of the portal triad, as reported by others, 4–8 might be related to a Preconditioning effect. If so, a short period of ischemia may protect the liver during subsequent liver resection performed under inflow occlusion. This effect should occur without increased blood loss as seen during intermittent clamping. To test this hypothesis, we designed a study involving 24 patients undergoing major hepatectomy. To minimize variability, we adopted a rigid protocol including fixed periods of prolonged clamping after Ischemic Preconditioning, and a standardized technique of hepatectomy performed by a single surgeon (P.A.C.). We also attempted to identify underlying mechanisms of injury and protection from Ischemic Preconditioning in these patients.
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protective effects of Ischemic Preconditioning for liver resection performed under inflow occlusion in humans
Annals of Surgery, 2000Co-Authors: Pierre-alain Clavien, Surinder S Yadav, David Sindram, Rex C BentleyAbstract:Clamping of the portal triad (inflow occlusion), also called the Pringle maneuver, is often used during liver surgery to minimize blood loss. Excessive blood loss during surgery and the need for transfusion have been shown to hinder the postoperative course. 1–3 Several recent clinical 4–6 and experimental 7,8 studies have demonstrated that intermittent clamping of the portal triad is better tolerated than prolonged continuous periods of ischemia. 5,6 However, the beneficial effect of intermittent clamping on Ischemic injury, as assessed by postoperative serum transaminase and bilirubin levels, is counterbalanced by increased blood loss during the various reperfusion periods. If the protective mechanisms of intermittent ischemia could be identified, then innovative strategies could be developed to protect the liver against Ischemic and reperfusion injury without increased blood loss. One strategy that could be applicable to hepatic surgery is Ischemic Preconditioning. Ischemic Preconditioning is a short period of ischemia followed by a brief period of reperfusion before a sustained Ischemic insult. Most of the data on Ischemic Preconditioning have been gathered in the heart, with a focus on the ability of Preconditioning to reduce the size of a myocardial infarction. A few of the involved extracellular mediators, such as adenosine 9 and nitric oxide, 10 have been identified. Protection by Ischemic Preconditioning has been subsequently documented in a variety of tissues, including skeletal muscle, 11 brain, 12 spinal cord, 13 retina, 14 and intestine, 15 and is thought to be part of a ubiquitous protective mechanism against repetitive stress on cells and cell systems. Only a few investigators have studied the effects of Ischemic Preconditioning in the liver, 16–21 and only data in rodents are available. These studies have suggested that the liver could also be protected against Ischemic insults by Preconditioning. We recently identified an Ischemic Preconditioning protocol (10 minutes of ischemia followed by 15 minutes of reperfusion) that completely prevented animal death in mice subjected to 75 minutes of total hepatic ischemia, a lethal condition without Preconditioning. 16 In view of our previous findings that apoptosis of sinusoidal endothelial cells and hepatocytes is a prominent feature of reperfusion injury in the warm Ischemic liver, 22 we also studied the effects of Ischemic Preconditioning on postreperfusion apoptosis in a mouse model of partial hepatic ischemia. 16 Ischemic Preconditioning was associated with complete abrogation of the massive hepatocellular apoptosis seen after prolonged periods of ischemia and downregulation of cytoplasmic caspase activities. Caspases are a family of cysteine proteases initiating complex proteolytic reactions leading to cell disassembly and death. 23 The beneficial effects of intermittent clamping of the portal triad, as reported by others, 4–8 might be related to a Preconditioning effect. If so, a short period of ischemia may protect the liver during subsequent liver resection performed under inflow occlusion. This effect should occur without increased blood loss as seen during intermittent clamping. To test this hypothesis, we designed a study involving 24 patients undergoing major hepatectomy. To minimize variability, we adopted a rigid protocol including fixed periods of prolonged clamping after Ischemic Preconditioning, and a standardized technique of hepatectomy performed by a single surgeon (P.A.C.). We also attempted to identify underlying mechanisms of injury and protection from Ischemic Preconditioning in these patients.
Gary P. Van Guilder - One of the best experts on this subject based on the ideXlab platform.
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No influence of Ischemic Preconditioning on running economy
European Journal of Applied Physiology, 2017Co-Authors: Gungeet Kaur, Megan Binger, Tiffany Trachte, Claire Evans, Gary P. Van GuilderAbstract:Purpose Many of the potential performance-enhancing properties of Ischemic Preconditioning suggest that the oxygen cost for a given endurance exercise workload will be reduced, thereby improving the economy of locomotion. The aim of this study was to identify whether Ischemic Preconditioning improves exercise economy in recreational runners. Methods A randomized sham-controlled crossover study was employed in which 18 adults (age 27 ± 7 years; BMI 24.6 ± 3 kg/m^2) completed two, incremental submaximal (65–85% V O_2max) treadmill running protocols (3 × 5 min stages from 7.2–14.5 km/h) coupled with indirect calorimetry to assess running economy following Ischemic Preconditioning (3 × 5 min bilateral upper thigh ischemia) and sham control. Running economy was expressed as mlO_2/kg/km and as the energy in kilocalories required to cover 1 km of horizontal distance (kcal/kg/km). Results Ischemic Preconditioning did not influence steady-state heart rate, oxygen consumption, minute ventilation, respiratory exchange ratio, energy expenditure, and blood lactate. Likewise, running economy was similar ( P = 0.647) between the sham (from 201.6 ± 17.7 to 204.0 ± 16.1 mlO_2/kg/km) and Ischemic Preconditioning trials (from 202.8 ± 16.2 to 203.1 ± 15.6 mlO_2/kg/km). There was no influence ( P = 0.21) of Ischemic Preconditioning on running economy expressed as the caloric unit cost (from 0.96 ± 0.12 to 1.01 ± 0.11 kcal/kg/km) compared with sham (from 1.00 ± 0.10 to 1.00 ± 0.08 kcal/kg/km). Conclusions The properties of Ischemic Preconditioning thought to affect exercise performance at vigorous to severe exercise intensities, which generate more extensive physiological challenge, are ineffective at submaximal workloads and, therefore, do not change running economy.
Gungeet Kaur - One of the best experts on this subject based on the ideXlab platform.
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No influence of Ischemic Preconditioning on running economy
European Journal of Applied Physiology, 2017Co-Authors: Gungeet Kaur, Megan Binger, Tiffany Trachte, Claire Evans, Gary P. Van GuilderAbstract:Purpose Many of the potential performance-enhancing properties of Ischemic Preconditioning suggest that the oxygen cost for a given endurance exercise workload will be reduced, thereby improving the economy of locomotion. The aim of this study was to identify whether Ischemic Preconditioning improves exercise economy in recreational runners. Methods A randomized sham-controlled crossover study was employed in which 18 adults (age 27 ± 7 years; BMI 24.6 ± 3 kg/m^2) completed two, incremental submaximal (65–85% V O_2max) treadmill running protocols (3 × 5 min stages from 7.2–14.5 km/h) coupled with indirect calorimetry to assess running economy following Ischemic Preconditioning (3 × 5 min bilateral upper thigh ischemia) and sham control. Running economy was expressed as mlO_2/kg/km and as the energy in kilocalories required to cover 1 km of horizontal distance (kcal/kg/km). Results Ischemic Preconditioning did not influence steady-state heart rate, oxygen consumption, minute ventilation, respiratory exchange ratio, energy expenditure, and blood lactate. Likewise, running economy was similar ( P = 0.647) between the sham (from 201.6 ± 17.7 to 204.0 ± 16.1 mlO_2/kg/km) and Ischemic Preconditioning trials (from 202.8 ± 16.2 to 203.1 ± 15.6 mlO_2/kg/km). There was no influence ( P = 0.21) of Ischemic Preconditioning on running economy expressed as the caloric unit cost (from 0.96 ± 0.12 to 1.01 ± 0.11 kcal/kg/km) compared with sham (from 1.00 ± 0.10 to 1.00 ± 0.08 kcal/kg/km). Conclusions The properties of Ischemic Preconditioning thought to affect exercise performance at vigorous to severe exercise intensities, which generate more extensive physiological challenge, are ineffective at submaximal workloads and, therefore, do not change running economy.
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No Influence of Ischemic Preconditioning on Running Economy
European Journal of Applied Physiology, 2016Co-Authors: Gungeet Kaur, Megan Binger, Tiffany Trachte, Claire Evans, Gary P. Van GuilderAbstract:Purpose Many of the potential performance-enhancing properties of Ischemic Preconditioning suggest that the oxygen cost for a given endurance exercise workload will be reduced, thereby improving the economy of locomotion. The aim of this study was to identify whether Ischemic Preconditioning improves exercise economy in recreational runners.
