Derek J Hausenloy

National Institute for Health Research, Londinium, England, United Kingdom

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Publications (211)1429.83 Total impact

  • Uma A Mukherjee · Sang-Bing Ong · Sang-Ging Ong · Derek J Hausenloy ·
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    ABSTRACT: Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia-reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantial nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death - through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection.
    Pharmacology [?] Therapeutics 10/2015; DOI:10.1016/j.pharmthera.2015.10.005 · 9.72 Impact Factor
  • Heerajnarain Bulluck · Derek J Hausenloy ·

    Revista Espanola de Cardiologia 10/2015; 68(11). DOI:10.1016/j.rec.2015.06.022 · 3.34 Impact Factor
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    ABSTRACT: Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/ reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention (n ¼ 8); (ii) RIPostC – with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (n ¼ 8). RIPostC reduced the hypoxic-ischemic-induced increase in white matter proton MRS lactate/N acetyl aspartate (p ¼ 0.005) and increased whole brain phosphorus-31 MRS ATP (p ¼ 0.039) over the 48 h after HI. Cell death was reduced with RIPostC in the periventricular white matter (p ¼ 0.03), internal capsule (p ¼ 0.002) and corpus callosum (p ¼ 0.021); there was reduced microglial activation in corpus callosum (p ¼ 0.001) and more surviving oligodendrocytes in corpus callosum (p ¼ 0.029) and periventricular white matter (p ¼ 0.001). Changes in gene expression were detected in the white matter at 48 h, including K ATP channel and endothelin A receptor. Immediate RIPostC is a potentially safe and promising brain protective therapy for babies with NE with protection in white but not grey matter.
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    ABSTRACT: 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 number, NCT01247545 .).
    New England Journal of Medicine 10/2015; DOI:10.1056/NEJMoa1413534 · 55.87 Impact Factor
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    ABSTRACT: Remote ischemic conditioning (RIC) using transient limb ischemia/reperfusion has been reported to reduce perioperative myocardial injury in patients undergoing coronary artery bypass grafting and/or valve surgery. The role of intravenous glyceryl trinitrate (GTN) therapy administered during cardiac surgery as a cardioprotective agent and whether it interferes with RIC cardioprotection is not clear and is investigated in the ERIC-GTN trial ( NCT01864252). The ERIC-GTN trial is a single-site, double-blind, randomized, placebo-controlled study. Consenting adult patients (age > 18 years) undergoing elective coronary artery bypass grafting +/- valve surgery with blood cardioplegia will be eligible for inclusion. Two hundred sixty patients will be randomized to 1 of 4 treatment groups following anesthetic induction: (1) RIC alone, a RIC protocol comprising three 5-minute cycles of simultaneous upper-arm and thigh cuff inflation/deflation followed by an intravenous (IV) placebo infusion; (2) GTN alone, a simulated sham RIC protocol followed by an IV GTN infusion; (3) RIC + GTN, a RIC protocol followed by an IV GTN infusion; and (4) neither RIC nor GTN, a sham RIC protocol followed by IV placebo infusion. The primary endpoint will be perioperative myocardial injury as quantified by the 72-hour area-under-the-curve serum high-sensitivity troponin T. The ERIC-GTN trial will determine whether intraoperative GTN therapy is cardioprotective during cardiac surgery and whether it affects RIC cardioprotection.
    Clinical Cardiology 09/2015; DOI:10.1002/clc.22445 · 2.59 Impact Factor
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    ABSTRACT: Background: Adenosine administered as an adjunct to reperfusion can reduce coronary no-reflow and limit myocardial infarct (MI) size in ST-segment elevation myocardial infarction (STEMI) patients. Whether adjunctive adenosine therapy can improve clinical outcomes in reperfused STEMI patients is not clear and is investigated in this meta-analysis of 13 randomized controlled trials (RCTs). Methods: We performed an up-to-date search for all RCTs investigating adenosine as an adjunct to reperfusion in STEMI patients. We calculated pooled relative risks using a fixed-effect meta-analysis assessing the impact of adjunctive adenosine therapy on major clinical endpoint including all-cause mortality, non-fatal myocardial infarction, and heart failure. Surrogate markers of reperfusion were also analyzed. Results: 13 RCTs (4273 STEMI patients) were identified and divided into 2 subgroups: intracoronary adenosine versus control (8 RCTs) and intravenous adenosine versus control (5 RCTs). In patients administered intracoronary adenosine, the incidence of heart failure was significantly lower (risk ratio [RR] 0.44 [95% CI 0.25-0.78], P=0.005) and the incidence of coronary no-reflow was reduced (RR for TIMI flow<3 postreperfusion 0.68 [95% CI 0.47-0.99], P=0.04). There was no difference in heart failure incidence in the intravenous adenosine group but most RCTs in this subgroup were from the thrombolysis era. There was no difference in non-fatal MI or all-cause mortality in both subgroups. Conclusion: We find evidence of improved clinical outcome in terms of less heart failure in STEMI patients administered intracoronary adenosine as an adjunct to reperfusion. This finding will need to be confirmed in a large adequately powered prospective RCT.
    International journal of cardiology 09/2015; 202:228-237. DOI:10.1016/j.ijcard.2015.09.005 · 4.04 Impact Factor
  • Heerajnarain Bulluck · Luciano Candilio · Derek J Hausenloy ·

    American Journal of Kidney Diseases 09/2015; DOI:10.1053/j.ajkd.2015.08.018 · 5.90 Impact Factor
  • Derek J Hausenloy · Derek M Yellon ·

    New England Journal of Medicine 08/2015; 373(11). DOI:10.1056/NEJMe1509718 · 55.87 Impact Factor
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    ABSTRACT: Whether T1-mapping cardiovascular magnetic resonance (CMR) can accurately quantify the area-at-risk (AAR) as delineated by T2 mapping and assess myocardial salvage at 3T in reperfused ST-segment elevation myocardial infarction (STEMI) patients is not known and was investigated in this study. 18 STEMI patients underwent CMR at 3T (Siemens Bio-graph mMR) at a median of 5 (4-6) days post primary percutaneous coronary intervention using native T1 (MOLLI) and T2 mapping (WIP #699; Siemens Healthcare, UK). Matching short-axis T1 and T2 maps covering the entire left ventricle (LV) were assessed by two independent observers using manual, Otsu and 2 standard deviation thresholds. Inter- and intra-observer variability, correlation and agreement between the T1 and T2 mapping techniques on a per-slice and per patient basis were assessed. A total of 125 matching T1 and T2 mapping short-axis slices were available for analysis from 18 patients. The acquisition times were identical for the T1 maps and T2 maps. 18 slices were excluded due to suboptimal image quality. Both mapping sequences were equally prone to susceptibility artifacts in the lateral wall and were equally likely to be affected by microvascular obstruction requiring manual correction. The Otsu thresholding technique performed best in terms of inter- and intra-observer variability for both T1 and T2 mapping CMR. The mean myocardial infarct size was 18.8 ± 9.4 % of the LV. There was no difference in either the mean AAR (32.3 ± 11.5 % of the LV versus 31.6 ± 11.2 % of the LV, P = 0.25) or myocardial salvage index (0.40 ± 0.26 versus 0.39 ± 0.27, P = 0.20) between the T1 and T2 mapping techniques. On a per-slice analysis, there was an excellent correlation between T1 mapping and T2 mapping in the quantification of the AAR with an R(2) of 0.95 (P < 0.001), with no bias (mean ± 2SD: bias 0.0 ± 9.6 %). On a per-patient analysis, the correlation and agreement remained excellent with no bias (R(2) 0.95, P < 0.0001, bias 0.7 ± 5.1 %). T1 mapping CMR at 3T performed as well as T2 mapping in quantifying the AAR and assessing myocardial salvage in reperfused STEMI patients, thereby providing an alternative CMR measure of the the AAR.
    Journal of Cardiovascular Magnetic Resonance 08/2015; 17(1):73. DOI:10.1186/s12968-015-0173-6 · 4.56 Impact Factor
  • Niall Burke · Andrew R Hall · Derek J Hausenloy ·
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    ABSTRACT: Mitochondria are known to play crucial roles in normal cellular physiology and in more recent years they have been implicated in a wide range of pathologies. Central to both these roles is their ability to alter their shape interchangeably between two different morphologies: an elongated interconnected network and a fragmented discrete phenotype - processes which are under the regulation of the mitochondrial fusion and fission proteins, respectively. In this review article, we focus on the mitochondrial fusion protein optic atrophy protein 1 (OPA1) in cardiovascular health and disease and we explore its role as a potential therapeutic target for treating cardiovascular and metabolic disease.
    Current Drug Targets 07/2015; 16(8). DOI:10.2174/1389450116666150102113648 · 3.02 Impact Factor

  • Journal of the American College of Cardiology 06/2015; 65(25):2764-5. DOI:10.1016/j.jacc.2015.02.082 · 16.50 Impact Factor
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    ABSTRACT: Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Archives of Disease in Childhood - Fetal and Neonatal Edition 06/2015; DOI:10.1136/archdischild-2014-306284 · 3.12 Impact Factor
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    ABSTRACT: The past decade has witnessed a number of exciting developments in the field of mitochondrial dynamics - a phenomenon in which changes in mitochondrial shape and movementimpact on cellular physiology and pathology. By undergoing fusion and fission, mitochondria are able to change their morphology between elongated interconnected networks and discrete fragmented structures, respectively. The cardiac mitochondria, in particular, have garnered much interest due to their unique spatial arrangement in the adult cardiomyocyte, and the multiple roles they play in cell death and survival. In this article, we review the role of the mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 05/2015; 763(Pt A). DOI:10.1016/j.ejphar.2015.04.056 · 2.53 Impact Factor
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    ABSTRACT: Novel therapies capable of reducing myocardial infarct (MI) size when administered prior to reperfusion are required to prevent the onset of heart failure in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). Experimental animal studies have demonstrated that mineralocorticoid receptor antagonist (MRA) therapy administered prior to reperfusion can reduce MI size, and MRA therapy prevents adverse left ventricular (LV) remodeling in post-MI patients with LV impairment. With these 2 benefits in mind, we hypothesize that initiating MRA therapy prior to PPCI, followed by 3 months of oral MRA therapy, will reduce MI size and prevent adverse LV remodeling in STEMI patients. The MINIMISE-STEMI trial is a prospective, randomized, double-blind, placebo-controlled trial that will recruit 150 STEMI patients from four centers in the United Kingdom. Patients will be randomized to receive either an intravenous bolus of MRA therapy (potassium canrenoate 200 mg) or matching placebo prior to PPCI, followed by oral spironolactone 50 mg once daily or matching placebo for 3 months. A cardiac magnetic resonance imaging scan will be performed within 1 week of PPCI and repeated at 3 months to assess MI size and LV remodeling. Enzymatic MI size will be estimated by the 48-hour area-under-the-curve serum cardiac enzymes. The primary endpoint of the study will be MI size on the 3-month cardiac magnetic resonance imaging scan. The MINIMISE STEMI trial will investigate whether early MRA therapy, initiated prior to reperfusion, can reduce MI size and prevent adverse post-MI LV remodeling. © 2015 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.
    Clinical Cardiology 05/2015; 38(5). DOI:10.1002/clc.22401 · 2.59 Impact Factor
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    ABSTRACT: Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff. Four hundred major vascular surgery patients in five Irish vascular centres will be randomised (stratified for centre and procedure) to undergo RIPC or not immediately before surgery. RIPC will be induced using a blood pressure cuff with four cycles of 5 minutes of ischaemia followed by 5 minutes of reperfusion immediately before the start of operations. There is no sham intervention. Participants will undergo serum troponin measurements pre-operatively and 1, 2, and 3 days post-operatively. Participants will undergo 12-lead electrocardiograms pre-operatively and on the second post-operative day. Predefined complications within one year of surgery will be recorded. Patient and staff experiences will be explored using qualitative techniques. The primary outcome measure is the proportion of patients who develop elevated serum troponin levels in the first 3 days post-operatively. Secondary outcome measures include length of hospital and critical care stay, unplanned critical care admissions, death, myocardial infarction, stroke, mesenteric ischaemia and need for renal replacement therapy (within 30 days of surgery). RIPC is novel intervention with the potential to significantly improve perioperative outcomes. This trial will provide the first evaluation of RIPC's ability to reduce adverse clinical events following major vascular surgery. NCT02097186 Date Registered: 24 March 2014.
    Trials 04/2015; 16(1):185. DOI:10.1186/s13063-015-0678-1 · 1.73 Impact Factor
  • Heerajnarain Bulluck · Derek J Hausenloy ·
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    ABSTRACT: To recognise that acute myocardial ischaemia/reperfusion injury is a neglected therapeutic target for cardioprotection that is responsible for the ongoing morbidity and mortality of patients with ischaemic heart disease. To be aware that cardiac bypass surgery and ST segment elevation myocardial infarction are the major clinical settings in which the heart is subjected to acute ischaemia/reperfusion injury. To be familiar with the concept of ‘ischaemic conditioning’, in which the heart is protected against acute ischaemia/reperfusion injury by subjecting it to cycles of brief ischaemia and reperfusion, a therapeutic strategy which has been demonstrated in proof-of-concept studies to be beneficial in patients with ischaemic heart disease.
    Heart (British Cardiac Society) 04/2015; 101(13). DOI:10.1136/heartjnl-2014-306531 · 5.60 Impact Factor
  • Sandrine Lecour · Rainer Schulz · Péter Ferdinandy · Derek J Hausenloy ·

    Cardiovascular Research 02/2015; 106(1). DOI:10.1093/cvr/cvv052 · 5.94 Impact Factor
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    Klaus T. Preissner · William A. Boisvert · Derek J Hausenloy ·

    Thrombosis and Haemostasis 02/2015; 113(3):439-440. DOI:10.1160/TH15-01-0086 · 4.98 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 02/2015; 17(1). DOI:10.1186/1532-429X-17-S1-O41 · 4.56 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 02/2015; 17(1). DOI:10.1186/1532-429X-17-S1-P8 · 4.56 Impact Factor

Publication Stats

10k Citations
1,429.83 Total Impact Points


  • 2015
    • National Institute for Health Research
      Londinium, England, United Kingdom
  • 2010-2015
    • Liverpool Heart And Chest Hospital
      Liverpool, England, United Kingdom
    • Duke University
      Durham, North Carolina, United States
  • 2008-2015
    • University College London
      • Institute of Cardiovascular Science
      Londinium, England, United Kingdom
  • 2014
    • University of Cape Town
      Kaapstad, Western Cape, South Africa
  • 2013
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
    • Oxford University Hospitals NHS Trust
      • Department of Cardiovascular Medicine
      Oxford, England, United Kingdom
  • 2011-2013
    • University College London Hospitals NHS Foundation Trust
      • Department of Cardiology
      Londinium, England, United Kingdom
  • 2012
    • University of California, San Diego
      • Skaggs School of Pharmacy and Pharmaceutical Sciences
      San Diego, CA, United States
  • 2009
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2005-2008
    • Novo Nordisk
      København, Capital Region, Denmark
    • Chelsea and Westminster Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2003-2007
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom