Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart.

Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic-however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing.

Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery.

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research.

Pre-clinical Experience with a Multi-Chordal Patch for Mitral Valve Repair.

Surgical repair of flail mitral valve leaflets with neochordoplasty has good outcomes, but implementing it in anterior and bi-leaflet leaflet repair is challenging. Placing and sizing individual neochordae is time consuming and error prone, with persistent localized flail if performed incorrectly. In this study, we report our pre-clinical experience with a novel multi-chordal patch for mitral valve repair.

Adenosine, lidocaine and Mg2+ improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model.

Introduction: The combination of Adenosine (A), lidocaine (L) and Mg(2+) (M) (ALM) has demonstrated cardioprotective and resuscitative properties in models of cardiac arrest and hemorrhagic shock. This study evaluates whether ALM also demonstrates organ protective properties in an endotoxemic porcine model.

Methods: Pigs (37 to 42 kg) were randomized into: 1) Control (n = 8) or 2) ALM (n = 8) followed by lipopolysaccharide infusion (1 μg ∙ kg(-1) ∙ h(-1)) for five hours.

Small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ has multiple benefits during hypotensive and blood resuscitation in the pig following severe blood loss: rat to pig translation.

Objectives: Currently, there is no effective small-volume fluid for traumatic hemorrhagic shock. Our objective was to translate small-volume 7.5% NaCl adenosine, lidocaine, and Mg hypotensive fluid resuscitation from the rat to the pig.

Automatic detection of left and right ventricles from CTA enables efficient alignment of anatomy with myocardial perfusion data.

Background: Accurate alignment between cardiac CT angiographic studies (CTA) and nuclear perfusion images is crucial for improved diagnosis of coronary artery disease. This study evaluated in an animal model the accuracy of a CTA fully automated biventricular segmentation algorithm, a necessary step for automatic and thus efficient PET/CT alignment.

Methods And Results: Twelve pigs with acute infarcts were imaged using Rb-82 PET and 64-slice CTA.

Hyperkalemic cardioplegia for adult and pediatric surgery: end of an era?

Despite surgical proficiency and innovation driving low mortality rates in cardiac surgery, the disease severity, comorbidity rate, and operative procedural difficulty have increased. Today's cardiac surgery patient is older, has a "sicker" heart and often presents with multiple comorbidities; a scenario that was relatively rare 20 years ago. The global challenge has been to find new ways to make surgery safer for the patient and more predictable for the surgeon.

The effects of adenocaine (adenosine and lidocaine) on early post-resuscitation cardiac and neurological dysfunction in a porcine model of cardiac arrest.

Aim: Return of spontaneous circulation (ROSC) elicits ischaemia/reperfusion injury and myocardial dysfunction. The combination of adenosine and lidocaine (AL, adenocaine) has been shown to (1) inhibit neutrophil inflammatory activation and (2) improve left ventricular function after ischaemia. We hypothesized that resuscitation with adenocaine during early moments of cardiopulmonary resuscitation (CPR) attenuates leucocyte oxidant generation and myocardial dysfunction.

Postconditioning attenuates acute intestinal ischemia-reperfusion injury.

The aim of this study was to test the hypothesis that postconditioning (POC) would reduce the detrimental effects of the acute intestinal ischemia-reperfusion (I/R) compared to those of the abrupt onset of reperfusion. POC has a protective effect on intestinal I/R injury by inhibiting events in the early minutes of reperfusion in rats. Twenty-four Wistar-Albino rats were subjected to the occlusion of superior mesenteric artery for 30 minutes, then reperfused for 120 minutes, and randomized to the four different modalities of POC: (1) control (no intervention); (2) POC-3 (three cycles of 10 seconds of reperfusion-reocclusion, 1 minute total intervention); (3) POC-6 (six cycles of 10 seconds of reperfusion-reocclusion, 2 minutes total intervention); and (4) sham operation (laparotomy only).

The science and clinical translation of remote postconditioning.

The treatment of reperfusion injury requires measures beyond timely reperfusion. Conventional postconditioning (PostC) of ischemic tissues offers a strategy to reduce reperfusion injury, but its adoption is challenged by requiring access and imposing additional ischemia to the ischemic organ. Generating protective signals by PostC in a tissue remote from the target organ such as the limb, i.

Adenocaine and Mg(2+) reduce fluid requirement to maintain hypotensive resuscitation and improve cardiac and renal function in a porcine model of severe hemorrhagic shock*.

Objectives: Hypotensive resuscitation is gaining clinical acceptance in the treatment of hemorrhagic shock. Our aims were to investigate: 1) the effect of 7.5% NaCl with adenocaine (adenosine and lidocaine, AL) and AL with Mg (ALM) on fluid requirement to maintain a minimum mean arterial pressure of 50 mm Hg, and 2) the effect of a second bolus of 0.

Ischemia-reperfusion increases transfection efficiency of intracoronary adenovirus type 5 in pig heart in situ.

Efficiency of intracoronary (IC) adenoviral vector transfection is impaired by the vascular endothelium. Ischemia and substances that increase vascular permeability (sodium nitroprusside, nitroglycerin) may augment adenoviral vector transfection efficiency (TE). We tested whether TE of adenoviral vector following IC infusion is improved by nitrates or by ischemia.

Endogenous cardioprotection by ischaemic postconditioning and remote conditioning.

Persistent myocardial ischaemia causes cell death if not rescued by early reperfusion. Millions of years in nature's laboratory have evolved protective responses that 'condition' the heart (and other tissues) to adapt to stressors, and these responses are applicable to the relatively new societal stress of myocardial ischaemia and reperfusion injury. Conditioning can be applied before (preconditioning), during (perconditioning), or after (postconditioning) the ischaemic stressor by imposing short periods of non-lethal ischaemia separated by brief periods of reperfusion.