T1 mapping and T2 mapping at 3T for quantifying the area-at-risk in reperfused STEMI patients.

Background: 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.

Methods: 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.

New horizons for newborn brain protection: enhancing endogenous neuroprotection.

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.

Mineralocorticoid receptor antagonist pretreatment to MINIMISE reperfusion injury after ST-elevation myocardial infarction (the MINIMISE STEMI Trial): rationale and study design.

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.

Mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease.

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 movement impact 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.

Remote ischaemic conditioning: cardiac protection from afar.

For patients with ischaemic heart disease, remote ischaemic conditioning may offer an innovative, non-invasive and virtually cost-free therapy for protecting the myocardium against the detrimental effects of acute ischaemia-reperfusion injury, preserving cardiac function and improving clinical outcomes. The intriguing phenomenon of remote ischaemic conditioning was first discovered over 20 years ago, when it was shown that the heart could be rendered resistant to acute ischaemia-reperfusion injury by applying one or more cycles of brief ischaemia and reperfusion to an organ or tissue away from the heart - initially termed 'cardioprotection at a distance'. Subsequent pre-clinical and then clinical studies made the important discovery that remote ischaemic conditioning could be elicited non-invasively, by inducing brief ischaemia and reperfusion to the upper or lower limb using a cuff.

Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

Background: Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways.

OPA1 in Cardiovascular Health and Disease.

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.

A retrospective analysis of myocardial preservation techniques during coronary artery bypass graft surgery: are we protecting the heart?

Background: Retrograde perfusion into coronary sinus during coronary artery bypass graft (CABG) surgery reduces the need for cardioplegic interruptions and ensures the distribution of cardioplegia to stenosed vessel territories, therefore enhancing the delivery of cardioplegia to the subendocardium. Peri-operative myocardial injury (PMI), as measured by the rise of serum level of cardiac biomarkers, has been associated with short and long-term clinical outcomes. We conducted a retrospective analysis to investigate whether the combination of antegrade and retrograde techniques of cardioplegia delivery is associated with a reduced PMI than that observed with the traditional methods of myocardial preservation.

Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop.

In 1993, Przyklenk and colleagues made the intriguing experimental observation that 'brief ischemia in one vascular bed also protects remote, virgin myocardium from subsequent sustained coronary artery occlusion' and that this effect'...

The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury.

Ischemic heart disease (IHD) remains the leading cause of death and disability worldwide. For patients presenting with an acute myocardial infarction, the most effective treatment for limiting myocardial infarct (MI) size is timely reperfusion. However, in addition to the injury incurred during acute myocardial ischemia, the process of reperfusion can itself induce myocardial injury and cardiomyocyte death, termed 'myocardial reperfusion injury', the combination of which can be referred to as acute ischemia-reperfusion injury (IRI).

Role of the MPTP in conditioning the heart - translatability and mechanism.

Mitochondria have long been known to be the gatekeepers of cell fate. This is particularly so in the response to acute ischaemia-reperfusion injury (IRI). Following an acute episode of sustained myocardial ischaemia, the opening of the mitochondrial permeability transition pore (MPTP) in the first few minutes of reperfusion, mediates cell death.

RNase1 prevents the damaging interplay between extracellular RNA and tumour necrosis factor-α in cardiac ischaemia/reperfusion injury.

Despite optimal therapy, the morbidity and mortality of patients presenting with an acute myocardial infarction (MI) remain significant, and the initial mechanistic trigger of myocardial "ischaemia/reperfusion (I/R) injury" remains greatly unexplained. Here we show that factors released from the damaged cardiac tissue itself, in particular extracellular RNA (eRNA) and tumour-necrosis-factor α (TNF-α), may dictate I/R injury. In an experimental in vivo mouse model of myocardial I/R as well as in the isolated I/R Langendorff-perfused rat heart, cardiomyocyte death was induced by eRNA and TNF-α.

ESC working group cellular biology of the heart: position paper: improving the preclinical assessment of novel cardioprotective therapies.

Ischaemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischaemia-reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes.

Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning.

Pre-, post-, and remote conditioning of the myocardium are well described adaptive responses that markedly enhance the ability of the heart to withstand a prolonged ischemia/reperfusion insult and provide therapeutic paradigms for cardioprotection. Nevertheless, more than 25 years after the discovery of ischemic preconditioning, we still do not have established cardioprotective drugs on the market. Most experimental studies on cardioprotection are still undertaken in animal models, in which ischemia/reperfusion is imposed in the absence of cardiovascular risk factors.

Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology.

The mechanism through which the protein kinase Akt (also called PKB), protects the heart against acute ischaemia-reperfusion injury (IRI) is not clear. Here, we investigate whether Akt mediates its cardioprotective effect by modulating mitochondrial morphology. Transfection of HL-1 cardiac cells with constitutively active Akt (caAkt) changed mitochondrial morphology as evidenced by an increase in the proportion of cells displaying predominantly elongated mitochondria (73 ± 5.

Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial.

Objectives: Remote ischaemic preconditioning (RIPC), using brief cycles of limb ischaemia/reperfusion, is a non-invasive, low-cost intervention that may reduce perioperative myocardial injury (PMI) in patients undergoing cardiac surgery. We investigated whether RIPC can also improve short-term clinical outcomes.

Methods: One hundred and eighty patients undergoing elective coronary artery bypass graft (CABG) surgery and/or valve surgery were randomised to receive either RIPC (2-5 min cycles of simultaneous upper arm and thigh cuff inflation/deflation; N=90) or control (uninflated cuffs placed on the upper arm and thigh; N=90).

Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction.

Objectives: This study aimed to determine whether remote ischemic conditioning (RIC) initiated prior to primary percutaneous coronary intervention (PPCI) could reduce myocardial infarct (MI) size in patients presenting with ST-segment elevation myocardial infarction.

Background: RIC, using transient limb ischemia and reperfusion, can protect the heart against acute ischemia-reperfusion injury. Whether RIC can reduce MI size, assessed by cardiac magnetic resonance (CMR), is unknown.

HIF-1 reduces ischaemia-reperfusion injury in the heart by targeting the mitochondrial permeability transition pore.

Aims: Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tolerance against acute myocardial ischaemia-reperfusion injury (IRI). However, the mechanism through which HIF-1 stabilization actually confers this cardioprotection is not clear. We investigated whether HIF-1α stabilization protects the heart against acute IRI by preventing the opening of the mitochondrial permeability transition pore (MPTP) and the potential mechanisms involved.

Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

Background: A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points.

Methods: Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists.