Diastolic Spontaneous Calcium Release From the Sarcoplasmic Reticulum Increases Beat-to-Beat Variability of Repolarization in Canine Ventricular Myocytes After β-Adrenergic Stimulation

Rationale: Spontaneous Ca2+ release (SCR) from the sarcoplasmic reticulum can cause delayed afterdepolarizations and triggered activity, contributing to arrhythmogenesis during β-adrenergic stimulation. Excessive beat-to-beat variability of repolarization duration (BVR) is a proarrhythmic marker. Previous research has shown that BVR is increased during intense β-adrenergic stimulation, leading to SCR. Objective:We aimed to determine ionic mechanisms controlling BVR under these conditions. Methods and Results:Membrane potentials and cell shortening or Ca2+ transients were recorded from isolated canine left ventricular myocytes in the presence of isoproterenol. Action-potential (AP) durations after delayed afterdepolarizations were significantly prolonged. Addition of slowly activating delayed rectifier K+ current (IKs) blockade led to further AP prolongation after SCR, and this strongly correlated with exaggerated BVR. Suppressing SCR via inhibition of ryanodine receptors, Ca2+/calmodulin-dependent protein kinase II inhibition, or by using Mg2+ or flecainide eliminated delayed afterdepolarizations and decreased BVR independent of effects on AP duration. Computational analyses and voltage-clamp experiments measuring L-type Ca2+ current (ICaL) with and without previous SCR indicated that ICaL was increased during Ca2+-induced Ca2+ release after SCR, and this contributes to AP prolongation. Prolongation of QT, Tpeak-Tend intervals, and left ventricular monophasic AP duration of beats after aftercontractions occurred before torsades de pointes in an in vivo dog model of drug-induced long-QT1 syndrome. Conclusions:SCR contributes to increased BVR by interspersed prolongation of AP duration, which is exacerbated during IKs blockade. Attenuation of Ca2+-induced Ca2+ release by SCR underlies AP prolongation via increased ICaL. These data provide novel insights into arrhythmogenic mechanisms during β-adrenergic stimulation besides triggered activity and illustrate the importance of IKs function in preventing excessive BVR

Introduction: New Approaches to Sustainable Offshore Food Production and the Development of Offshore platforms

As we exhaust traditional natural resources upon which we have relied for decades to support economic growth, alternatives that are compatible with a resource conservation ethic, are consistent with efforts to limit greenhouse emissions to combat global climate change, and that support principles of integrated coastal management must be identified. Examples of sectors that are prime candidates for reinvention are electrical generation and seafood production. Once a major force in global economies and a symbol of its culture and character, the fishing industry has experienced major setbacks in the past half-decade. Once bountiful fisheries were decimated by overfishing and destructive fisheries practices that resulted in tremendous biomass of discarded by-catch. Severe restrictions on landings and effort that have been implemented to allow stocks to recover have had tremendous impact on the economy of coastal communities. During the period of decline and stagnation in capture fisheries, global production from aquaculture grew dramatically, and now accounts for 50% of the world’s edible seafood supply. With the convergence of environmental and aesthetic concerns, aquaculture, which was already competing for space with other more established and accepted uses, is having an increasingly difficult time expanding in nearshore waters. Given the constraints on expansion of current methods of production, it is clear that alternative approaches are needed in order for the marine aquaculture sector to make a meaningful contribution to global seafood supply. Farming in offshore marine waters has been identified as one potential option for increasing seafood production and has been a focus of international attention for more than a decade. Though there are technical challenges for farming in the frequently hostile open ocean environment, there is sufficient rationale for pursuing the development of offshore farming. Favorable features of open ocean waters include ample space for expansion, tremendous carrying and assimilative capacity, reduced conflict with many user groups, lower exposure to human sources of pollution, the potential to reduce some of the negative environmental impacts of coastal fish farming (Ryan 2004; Buck 2004; Helsley and Kim 2005; Ward et al. 2006; Langan 2007), and optimal environmental conditions for a wide variety of marine species (Ostrowski and Helsley 2003; Ryan 2004; Howell et al. 2006; Benetti et al. 2006; Langan and Horton 2003). Those features, coupled with advances in farming technology (Fredheim and Langan 2009) would seem to present an excellent opportunity for growth, however, development in offshore waters has been measured. This has been due in large part to the spill over from the opposition to nearshore marine farming and the lack of a regulatory framework for permitting, siting and managing industry development. Without legal access to favorable sites and a “social license” to operate without undue regulatory hardship, it will be difficult for open ocean aquaculture to realize its true potential. Some parallels can be drawn between ocean aquaculture and electricity generation. Continued reliance on traditional methods of production, which for electricity means fossil fuels, is environmentally and economically unsustainable. There is appropriate technology available to both sectors, and most would agree that securing our energy and seafood futures are in the collective national interest. The most advanced and proven renewable sector for ocean power generation is wind turbines, and with substantial offshore wind resources in the, one would think there would be tremendous potential for development of this sector and public support for development. The casual observer might view the ocean as a vast and barren place, with lots of space to put wind turbines and fish farms. However, if we start to map out existing human uses such as shipping lanes, pipelines, cables, LNG terminals, and fishing grounds, and add to that ecological resource areas that require some degree of protection such as whale and turtle migration routes, migratory bird flyways, spawning grounds, and sensitive habitats such as corals, the ocean begins to look like a crowed place. Therefore, when trying to locate new ocean uses, it may be worthwhile to explore possibilities for co-location of facilities, in this case wind turbines and fish and shellfish farms. While some might argue that trying to co-locate two activities that are individually controversial would be a permitting nightmare, general agreement can probably be reached that there are benefits to be gained by reducing the overall footprint of human uses in the ocean. Meeting the challenges of multi-use facilities in the open ocean will require careful analysis and planning; however, the opportunity to co-locate sustainable seafood and renewable energy production facilities is intriguing, the concept is consistent with the goals of Marine Spatial Planning and ecosystem based management, and therefore worthy of pursuit

Computational models in cardiology

The treatment of individual patients in cardiology practice increasingly relies on advanced imaging, genetic screening and devices. As the amount of imaging and other diagnostic data increases, paralleled by the greater capacity to personalize treatment, the difficulty of using the full array of measurements of a patient to determine an optimal treatment seems also to be paradoxically increasing. Computational models are progressively addressing this issue by providing a common framework for integrating multiple data sets from individual patients. These models, which are based on physiology and physics rather than on population statistics, enable computational simulations to reveal diagnostic information that would have otherwise remained concealed and to predict treatment outcomes for individual patients. The inherent need for patient-specific models in cardiology is clear and is driving the rapid development of tools and techniques for creating personalized methods to guide pharmaceutical therapy, deployment of devices and surgical interventions