Enhancing gap junction coupling in reperfused myocardium

The work in this thesis sought to examine the effects of enhancing cardiac gap junction coupling using the pharmacological agent Rotigaptide in clinically applicable models of acute myocardial infarction. Specifically, the studies in this thesis investigated the effect of Rotigaptide on ventricular arrhythmogenesis and structural remodelling of the reperfused substrate, with particular emphasis on the development, application and histological validation of diffusion tensor magnetic resonance imagine (DTI) as a novel imaging modality to describe and quantify structural remodelling post-infarction. An ex vivo rat model of acute regional ischaemia-reperfusion was characterised and used to study the effect of Rotigaptide on ventricular arrhythmogenesis during acute ischaemia and reperfusion. Arrhythmias occurred during ischaemia in a monomodal distribution with a peak incidence between 12-15 minutes after ischaemia. The incidence of reperfusion arrhythmias was dependent on the preceding duration of ischaemia with a progressive reduction as ischaemic time extended from 15 to 60 minutes. Rotigaptide pre-treatment afforded a significant reduction in ischaemia-induced arrhythmias compared to administration at the onset of ischaemia or at the time of reperfusion. An in vivo rat model of infarction-reperfusion, mimicking clinical reperfusion in the setting of acute MI was characterised and Rotigaptide administered prior to reperfusion and for a week post-MI. At four-weeks post-MI animals were studied with 6-lead ECG, ambulatory telemetry, programmed electrical simulation (PES), optical mapping, DTI and histology. Rotigaptide reduced the susceptibility to arrhythmias induced by PES and partially restored DTI-derived indices of tissue disruption in infarcted myocardium.Open Acces

Mild stroke symptoms as the initial presentation of a patient with underlying subacute bacterial endocarditis

We describe a patient with sub-acute bacterial endocarditis, whose chief presenting feature was mild expressive dysphasia

Can Bivalve Habitat Restoration Improve Degraded Estuaries?

Bivalve habitats were once a dominant ecosystem in temperate and subtropical estuaries worldwide. While bivalve habitats are greatly reduced from their former abundance, remnant, and restored populations have been shown to provide a suite of important ecosystems services including improving water quality, coastal protection, and providing fisheries nursery habitat, in addition to providing a direct food value. Although it is unlikely that bivalve habitats can be brought back to their former abundance in most locations, bivalve restoration has been shown to be possible at large scale if the drivers of decline have been addressed. Restoring bivalve habitats can improve the health of estuaries, but restoration activities need to be supplemented with improved management practices, including in the surrounding catchments. Taking an estuary-wide approach to restoration, with bivalve habitat restoration complementing the restoration of other habitat types such as seagrasses, salt marshes, and mangroves is likely to yield both greater ecosystem benefits and may result in positive feedbacks resulting in greater restoration success of complimentary habitats. Motivation for bivalve and other coastal habitat restoration has moved beyond simply restoring an imperiled ecosystem and its biodiversity, to restoring food security, local employment, green engineering, shoreline protection, and nutrient trading. In the future it is likely that innovative engineering solutions will improve the success and value of bivalve habitat restoration. In addition to restoring natural bivalve habitats and the benefits that they bring to estuaries and the people who depend on them, novel solutions to improving estuary health and food security should be considered. There are likely to be benefits from using bivalve aquaculture as a tool for ecosystem modification (e.g., harnessing the filtering power of bivalves at high densities to improve local water quality) and creating green engineering solutions that include living elements such as bivalves to protect shorelines. © 2019 Copyrigh

Rotigaptide Infusion for the First 7 Days After Myocardial Infarction-Reperfusion Reduced Late Complexity of Myocardial Architecture of the Healing Border-Zone and Arrhythmia Inducibility

BACKGROUND: Survivors of myocardial infarction are at increased risk of late ventricular arrhythmias, with infarct size and scar heterogeneity being key determinants of arrhythmic risk. Gap junctions facilitate the passage of small ions and morphogenic cell signaling between myocytes. We hypothesized that gap junctions enhancement during infarction–reperfusion modulates structural and electrophysiological remodeling and reduces late arrhythmogenesis. METHODS AND RESULTS: Infarction–reperfusion surgery was carried out in male Sprague‐Dawley rats followed by 7 days of rotigaptide or saline administration. The in vivo and ex vivo arrhythmogenicity was characterized by programmed electrical stimulation 3 weeks later, followed by diffusion‐weighted magnetic resonance imaging and Masson's trichrome histology. Three weeks after 7‐day postinfarction administration of rotigaptide, ventricular tachycardia/ventricular fibrillation was induced on programmed electrical stimulation in 20% and 53% of rats, respectively (rotigaptide versus control), resulting in reduction of arrhythmia score (3.2 versus 1.4, P=0.018), associated with the reduced magnetic resonance imaging parameters fractional anisotropy (fractional anisotropy: −5% versus −15%; P=0.062) and mean diffusivity (mean diffusivity: 2% versus 6%, P=0.042), and remodeling of the 3‐dimensional laminar structure of the infarct border zone with reduction of the mean (16° versus 19°, P=0.013) and the dispersion (9° versus 12°, P=0.015) of the myofiber transverse angle. There was no change in ECG features, spontaneous arrhythmias, or mortality. CONCLUSIONS: Enhancement of gap junctions function by rotigaptide administered during the early healing phase in reperfused infarction reduces later complexity of infarct scar morphology and programmed electrical stimulation–induced arrhythmias, and merits further exploration as a feasible and practicable intervention in the acute myocardial infarction management to reduce late arrhythmic risk

Determinants of new wavefront locations in cholinergic atrial fibrillation

Atrial fibrillation (AF) wavefront dynamics are complex and difficult to interpret, contributing to uncertainty about the mechanisms that maintain AF. We aimed to investigate the interplay between rotors, wavelets, and focal sources during fibrillation