Preparing for a Northwest Passage: A Workshop on the Role of New England in Navigating the New Arctic

Preparing for a Northwest Passage: A Workshop on the Role of New England in Navigating the New Arctic (March 25 - 27, 2018 -- The University of New Hampshire) paired two of NSF\u27s 10 Big Ideas: Navigating the New Arctic and Growing Convergence Research at NSF. During this event, participants assessed economic, environmental, and social impacts of Arctic change on New England and established convergence research initiatives to prepare for, adapt to, and respond to these effects. Shipping routes through an ice-free Northwest Passage in combination with modifications to ocean circulation and regional climate patterns linked to Arctic ice melt will affect trade, fisheries, tourism, coastal ecology, air and water quality, animal migration, and demographics not only in the Arctic but also in lower latitude coastal regions such as New England. With profound changes on the horizon, this is a critical opportunity for New England to prepare for uncertain yet inevitable economic and environmental impacts of Arctic change

Optimising Large Animal Models of Sustained Atrial Fibrillation: Relevance of the Critical Mass Hypothesis

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-04-04, accepted 2021-05-24, epub 2021-06-15Publication status: PublishedBackground: Large animal models play an important role in our understanding of the pathophysiology of atrial fibrillation (AF). Our aim was to determine whether prospectively collected baseline variables could predict the development of sustained AF in sheep, thereby reducing the number of animals required in future studies. Our hypothesis was that the relationship between atrial dimensions, refractory periods and conduction velocity (otherwise known as the critical mass hypothesis) could be used for the first time to predict the development of sustained AF. Methods: Healthy adult Welsh mountain sheep underwent a baseline electrophysiology study followed by implantation of a neurostimulator connected via an endocardial pacing lead to the right atrial appendage. The device was programmed to deliver intermittent 50 Hz bursts of 30 s duration over an 8-week period whilst sheep were monitored for AF. Results: Eighteen sheep completed the protocol, of which 28% developed sustained AF. Logistic regression analysis showed only fibrillation number (calculated using the critical mass hypothesis as the left atrial diameter divided by the product of atrial conduction velocity and effective refractory period) was associated with an increased likelihood of developing sustained AF (Ln Odds Ratio 26.1 [95% confidence intervals 0.2–52.0] p = 0.048). A receiver-operator characteristic curve showed this could be used to predict which sheep developed sustained AF (C-statistic 0.82 [95% confidence intervals 0.59–1.04] p = 0.04). Conclusion: The critical mass hypothesis can be used to predict sustained AF in a tachypaced ovine model. These findings can be used to optimise the design of future studies involving large animals

The origin of T-tubules

Ring-like structures made up of caveolae appear to drive the development of membrane invaginations called T-tubules which are important for muscle contraction

How cardiomyocyte excitation, calcium release and contraction become altered with age.

AbstractCardiovascular disease is the main cause of death globally, accounting for over 17 million deaths each year. As the incidence of cardiovascular disease rises markedly with age, the overall risk of cardiovascular disease is expected to increase dramatically with the aging of the population such that by 2030 it could account for over 23 million deaths per year. It is therefore vitally important to understand how the heart remodels in response to normal aging for at least two reasons: i) to understand why the aged heart is increasingly susceptible to disease; and ii) since it may be possible to modify treatment of disease in older adults if the underlying substrate upon which the disease first develops is fully understood. It is well known that age modulates cardiac function at the level of the individual cardiomyocyte. Generally, in males, aging reduces cell shortening, which is associated with a decrease in the amplitude of the systolic Ca2+ transient. This may arise due to a decrease in peak L-type Ca2+ current. Sarcoplasmic reticulum (SR) Ca2+ load appears to be maintained during normal aging but evidence suggests that SR function is disrupted, such that the rate of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA)-mediated Ca2+ removal is reduced and the properties of SR Ca2+ release in terms of Ca2+ sparks are altered. Interestingly, Ca2+ handling is modulated by age to a lesser degree in females. Here we review how cellular contraction is altered as a result of the aging process by considering expression levels and functional properties of key proteins involved in controlling intracellular Ca2+. We consider how changes in both electrical properties and intracellular Ca2+ handling may interact to modulate cardiomyocyte contraction. We also reflect on why cardiovascular risk may differ between the sexes by highlighting sex-specific variation in the age-associated remodeling process. This article is part of a Special Issue entitled CV Aging

Cardiac Transverse Tubules in Physiology and Heart Failure.

From PubMed via Jisc Publications RouterPublication status: aheadofprintIn mammalian cardiac myocytes, the plasma membrane includes the surface sarcolemma but also a network of membrane invaginations called transverse (t-) tubules. These structures carry the action potential deep into the cell interior, allowing efficient triggering of Ca release and initiation of contraction. Once thought to serve as rather static enablers of excitation-contraction coupling, recent work has provided a newfound appreciation of the plasticity of the t-tubule network's structure and function. Indeed, t-tubules are now understood to support dynamic regulation of the heartbeat across a range of timescales, during all stages of life, in both health and disease. This review article aims to summarize these concepts, with consideration given to emerging t-tubule regulators and their targeting in future therapies. Expected final online publication date for the , Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates

Balanced changes in Ca buffering by SERCA and troponin contribute to Ca handling during β-adrenergic stimulation in cardiac myocytes

AIMS: During activation of cardiac myocytes, less than 1% of cytosolic Ca is free; the rest is bound to buffers, largely SERCA, and troponin C. Signalling by phosphorylation, as occurs during β-adrenergic stimulation, changes the Ca-binding affinity of these proteins and may affect the systolic Ca transient. Our aim was to determine the effects of β-adrenergic stimulation on Ca buffering and to differentiate between the roles of SERCA and troponin. METHODS AND RESULTS: Ca buffering was studied in cardiac myocytes from mice: wild-type (WT), phospholamban-knockout (PLN-KO), and mice expressing slow skeletal troponin I (ssTnI) that is not protein kinase A phosphorylatable. WT cells showed no change in Ca buffering in response to the β-adrenoceptor agonist isoproterenol (ISO). However, ISO decreased Ca buffering in PLN-KO myocytes, presumably unmasking the role of troponin. This effect was confirmed in WT cells in which SERCA activity was blocked with the application of thapsigargin. In contrast, ISO increased Ca buffering in ssTnI cells, presumably revealing the effect of an increase in Ca binding to SERCA. CONCLUSIONS: These data indicate the individual roles played by SERCA and troponin in Ca buffering during β-adrenergic stimulation and that these two buffers effectively counterbalance each other so that Ca buffering remains constant during β-adrenergic stimulation, a factor which may be physiologically important. This study also emphasizes the importance of taking into account Ca buffering, particularly in disease states where Ca binding to myofilaments or SERCA may be altered