Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. Substantial evidence indicates that cardiomyocytes located in the pulmonary veins [pulmonary vein sleeve cells (PVCs)] cause AF by generating ectopic electrical activity. Electrical ablation, isolating PVCs from their left atrial junctions, is a major treatment for AF. In small rodents, the sleeve of PVCs extends deep inside the lungs and is present in lung slices. Here we present data, using the lung slice preparation, characterizing how spontaneous Ca2+ transients in PVCs affect their capability to respond to electrical pacing. Immediately after a spontaneous Ca2+ transient the cell is in a refractory period and it cannot respond to electrical stimulation. Consequently, we observe that the higher the level of spontaneous activity in an individual PVC, the less likely it is that this PVC responds to electrical field stimulation. The spontaneous activity of neighbouring PVCs can be different from each other. Heterogeneity in the Ca2+ signalling of cells and in their responsiveness to electrical stimuli are known pro-arrhythmic events. The tendency of PVCs to show spontaneous Ca2+ transients and spontaneous action potentials (APs) underlies their potential to cause AF.
Much effort is focussed on understanding the structural and functional changes in the heart that underlie age-dependent deterioration of cardiac performance. Longitudinal studies, using aged animals, have pinpointed changes occurring to the contractile myocytes within the heart. However, whilst longitudinal studies are important, other experimental approaches are being advanced that can recapitulate the phenotypic changes seen during ageing. This study investigated the induction of an ageing cardiomyocyte phenotypic change by incubation of cells with hydroxyurea for several days ex vivo. Hydroxyurea incubation has been demonstrated to phenocopy age- and senescence-induced changes in neurons, but its utility for ageing studies with cardiac cells has not been examined. Incubation of neonatal rat ventricular myocytes with hydroxyurea for up to 7 days replicated specific aspects of cardiac ageing including reduced systolic calcium responses, increased alternans and a lesser ability of the cells to follow electrical pacing. Additional functional and structural changes were observed within the myocytes that pointed to ageing-like remodelling, including lipofuscin granule accumulation, reduced mitochondrial membrane potential, increased production of reactive oxygen species, and altered ultrastructure, such as mitochondria with disrupted cristae and disorganised myofibres. These data highlight the utility of alternative approaches for exploring cellular ageing whilst avoiding the costs and co-morbid factors that can affect longitudinal studies.
The water quality of the Susquehanna River, a major freshwater tributary of the Chesapeake Bay, significantly affects the aquatic health of the Bay. Following major storms in which the river flow rate exceeds 300,000 cubic feet per second (cfs), nutrients and sediment stored in the Lower Susquehanna Reservoir are deposited into the Chesapeake Bay. These excess nutrients facilitate algae blooms that hinder the growth of sub-aquatic vegetation (SAV) and harm the Bay's aquatic species. The Conowingo Dam, on the Lower Susquehanna River, is estimated to be at 85% of its sediment capacity. To reduce the sediment backlog, three dam sediment management alternatives have been identified: (i) No Mitigation, (ii) removal of sediment by Hydraulic Dredging and (iii) removal of sediment byHydraulic Dredging and increasing the bottom shear velocity to avoid sediment build-up. A utility analysis conducted using a fluid mechanics, ecological impact and business model indicates annual removal of sediment at 5,000,000 cubic yards to produce slag product, with the instantiation of a flow diverter to increase bottom shear stress to be the best alternative.
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