Remote Ischemic Preconditioning induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway.

Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in remote ischemic preconditioning (RIPC)-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by a 30-min transient blockade of the left coronary artery to simulate ischemia reperfusion (I/R) injury.

Circulating mediators of remote ischemic preconditioning: search for the missing link between non-lethal ischemia and cardioprotection.

Acute myocardial infarction (AMI) is one of the leading causes of mortality and morbidity worldwide. There has been an extensive search for cardioprotective therapies to reduce myocardial ischemia-reperfusion (I/R) injury. Remote ischemic preconditioning (RIPC) is a phenomenon that relies on the body's endogenous protective modalities against I/R injury.

Environmental stress and vestibular inputs modulate cardiovascular responses to orthostasis in hypertensive rats.

The frequent accompaniment of hypertension by orthostatic circulatory disorders prompted us to investigate the effect of repeated and sustained head-up and head-down tilt positions on cardiovascular responses in spontaneously hypertensive rats vs. Wistar rats using radiotelemetric implants. Repeated orthostasis caused a transient elevation in blood pressure (7.

Translation of Methodology Used In Human Myocardial Imaging to a Sheep Model of Acute Myocardial Infarction.

Introduction: Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly uses rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging (MPI) could be used for assessing sheep myocardium following an acute myocardial infarction (MI) and response to intervention.

Methods: Eighteen sheep were enrolled in a pilot study to evaluate [(99m)Tc]-sestamibi MPI at baseline, post-MI and after therapy.

Arrhythmogenicity of hypothermia - a large animal model of hypothermia.

Background: Therapeutic hypothermia (TH) is used to mitigate cerebral injury after an out of hospital cardiac arrest. There is a perceived risk of increased arrhythmias with temperatures lower than the current target of 32-34°C for TH. This study sought to develop and investigate the electrophysiological changes in a sheep model of systemic hypothermia regarding the susceptibility to ventricular arrhythmias.

Selective inhibition of the master regulator transcription factor Egr-1 with catalytic oligonucleotides reduces myocardial injury and improves left ventricular systolic function in a preclinical model of myocardial infarction.

Background: Egr-1 is implicated in the pathogenesis of myocardial ischemia-reperfusion injury. The aim of this study was to ascertain the effectiveness of intracoronary delivery of DNAzyme targeting the transcription factor Egr-1 at reperfusion following experimental myocardial ischemia.

Methods And Results: Functional DNAzyme targeting Egr-1 or a size-matched scrambled control were delivered via the intracoronary route immediately on reperfusion after 60 minutes' balloon occlusion of the left anterior descending coronary artery in a pig model of myocardial I/R injury (n=7 per treatment group).

Nonsurround, nonuniform, biventricular-capable direct cardiac compression provides Frank-Starling recruitment independent of left ventricular septal damage.

Objectives: Right ventricular (RV) function is compromised in 25% of left ventricular (LV) assist device recipients despite effective LV support. The risk of such dysfunction has been enhanced by an ischemic or undamaged interventricular septum; however, we found septal infarction to be paradoxically protective. We, therefore, evaluated the potential of nonsurround, nonuniform, biventricular-capable direct cardiac compression (DCC) (using the HeartPatch DCC) to overcome RV dysfunction in hearts with a normal or infarcted interventricular septum.

β(3) adrenergic stimulation of the cardiac Na+-K+ pump by reversal of an inhibitory oxidative modification.

Background: inhibition of L-type Ca(2+) current contributes to negative inotropy of β(3) adrenergic receptor (β(3) AR) activation, but effects on other determinants of excitation-contraction coupling are not known. Of these, the Na(+)-K(+) pump is of particular interest because of adverse effects attributed to high cardiac myocyte Na(+) levels and upregulation of the β(3) AR in heart failure.

Methods And Results: we voltage clamped rabbit ventricular myocytes and identified electrogenic Na(+)-K(+) pump current (I(p)) as the shift in holding current induced by ouabain.

Chronic septal infarction confers right ventricular protection during mechanical left ventricular unloading.

Objective: Right ventricular failure manifests in 25% of left ventricular assist device recipients because of ventricular coupling mechanism disruption. Septal ischemia accentuates this process, but the effect of septal infarction has not been elucidated. Right ventricular response to incremental left ventricular unloading was studied in sheep with septal infarction.

The Royal North Shore Hospital inquiry: an analysis of the recommendations and the implications for quality and safety in Australian public hospitals.

In October 2007, the New South Wales Parliament appointed a Joint Select Committee to inquire into the quality of patient care at Royal North Shore Hospital (RNSH). The inquiry was initiated in response to the publicity and complaints surrounding a patient who had a miscarriage in the toilets of the RNSH emergency department waiting area. The Committee held four public hearings and received 103 submissions.

Mesenchymal stem cells: isolation, characterisation and in vivo fluorescent dye tracking.

Cell therapies have been used to regenerate the heart by direct myocardial delivery, by coronary infusion and by surface attached scaffolds. Multipotent mesenchymal stem cells (MSC) with capacity to differentiate into cardiomyocytes and other cell lines have been predominantly trialled in rodents. However, large animal models are increasingly needed to translate basic research into new, safe regenerative therapies.

Time-dependent response of both ventricles after septal ablation: implications for biventricular support after left ventricular assist device placement.

Objectives: An ovine model of septal ablation was studied to elucidate the mechanisms involved in right ventricular failure when commencing left ventricular mechanical assistance. The disruption of ventricular interdependence after acute and chronic septal injury was examined.

Methods: Twelve sheep underwent percutaneous transluminal septal myocardial ablation using 0.

Effect of direct cardiac compression on left ventricular axial dynamics in sheep.

The HeartPatch direct cardiac compression device consists of two separate, nonsurround patches placed on the left and right ventricular free walls. Although the device has been shown to effectively restore circulatory parameters in acute heart failure sheep, the impact of device inflation on left ventricular geometry is yet to be elucidated. This study used sonomicrometer crystal transducers to examine three orthogonal left ventricular dimensions under various cardiac states and assessed the feasibility of determining stroke volume from these dimensions.

Efficacy and mechanisms of biventricular and left/right direct cardiac compression in acute heart failure sheep.

Direct cardiac compression (DCC) with implanted heart patches has previously demonstrated efficacy of biventricular (BiV) support in acute heart failure (HF) sheep. We hypothesized that this was primarily due to a left ventricular (LV) effect. This study compared BiV, LV, and right ventricular (RV) assists in terms of hemodynamic and energetic response.

Myocardial extracellular matrix remodeling in ischemic heart failure.

Left ventricular (LV) remodeling is a process whereby structural alterations attempt to compensate altered hemodynamic load. In the chronic setting this process becomes maladaptive, self-sustaining and is associated with worsened survival. The extracellular matrix (ECM) of the heart, once believed an inert scaffold for cardiomyocytes, is now known to play an important role in LV remodeling.

Postural effects when cycling in late pregnancy.

Aim: This study assessed if upright cycling is preferable to semi-recumbent cycling during pregnancy.

Method: Healthy women with low risk singleton pregnancies were tested at 34-38 weeks gestation. They cycled for 12 min, either semi-recumbent (45 degrees, n = 27) or upright (n = 23), at 135-145 beats min(-1).

Regional cardiac dysfunction is associated with specific alterations in inflammatory cytokines and matrix metalloproteinases after acute myocardial infarction in sheep.

Cardiac remodeling following myocardial infarction (MI) is a maladaptive process, fundamental to the progression of ischemic heart failure. The extent of remodeling is influenced by mechanical stress, inflammatory response and activation of matrix metalloproteinases (MMPs). This study examined regional association between these parameters in response to acute MI.

Remodeling of the chronic severely failing ischemic sheep heart after coronary microembolization: functional, energetic, structural, and cellular responses.

The mandatory use of pharmacotherapy in human heart failure (HF) impedes further study of natural history and remodeling mechanisms. We created a sheep model of chronic, severe, ischemic HF [left ventricular (LV) ejection fraction (LVEF) <35% stable over 4 wk] by selective coronary microembolization under general anesthesia and followed hemodynamic, energetic, neurohumoral, structural, and cellular responses over 6 mo. Thirty-eight sheep were induced into HF (58% success), with 23 sheep followed for 6 mo (21 sheep with sufficient data for analysis) after the LVEF stabilized (median of 3 embolizations).

Glucose-insulin-potassium solution improves left ventricular energetics in chronic ovine diabetes.

Background: Therapeutic modulation of myocardial metabolism improves outcomes in diabetic patients following myocardial infarction and coronary artery surgery. However, the mechanism of this beneficial effect has not been fully elucidated. This study evaluated the effect of glucose-insulin-potassium solution (GIK) on left ventricular (LV) energetics and oxygen utilization efficiency in a chronic ovine model of diabetes.

HeartPatch implanted direct cardiac compression: effect on coronary flow and flow patterns in acute heart failure sheep.

A novel HeartPatch direct cardiac compression (DCC) device has been shown to effectively restore circulatory parameters in sheep with acute heart failure (HF). Its effect on the coronary circulation and myocardial perfusion, however, remains uncertain. The effect of DCC assist on coronary artery blood flow (CABF) and its patterns in acute HF sheep were examined in this study.

Cardiomyocyte apoptosis is associated with increased wall stress in chronic failing left ventricle.

Aims: We examined cardiomyocyte apoptosis in chronic heart failure (HF) and its possible link to elevated wall stress.

Methods And Results: Moderate HF was produced in sheep by sequential coronary microembolization. Six months later, the animals remained in a stable compensated haemodynamic state of HF.

Direct compression of the failing heart reestablishes maximal mechanical efficiency.

Background: In failing hearts, homeostatic mechanisms contrive to maximize stroke work and maintain normal arterial blood pressure at the expense of energetic efficiency. In contrast dobutamine reestablishes maximal mechanical efficiency by promoting energetically optimal loading conditions. However, dobutamine also wastefully increases nonmechanical oxygen consumption.