Libin Cardiovascular Institute of Alberta

About: Libin Cardiovascular Institute of Alberta is a facility organization based out in Calgary, Alberta, Canada. It is known for research contribution in the topics: Population & Atrial fibrillation. The organization has 758 authors who have published 1459 publications receiving 44418 citations.

Molecular Mechanism of Conductance Enhancement in Narrow Cation-Selective Membrane Channels.

Abstract: Membrane proteins known as ryanodine receptors (RyRs) display large conductance of ∼1 nS and nearly ideal charge selectivity. Both properties are inversely correlated in other large-conductance but nonselective biological nanopores (i.e., α-hemolysin) used as industrial biosensors. Although recent cryo-electron microscopy structures of RyR2 show similarities to K+- and Na+-selective channels, it remains unclear whether similar ion conduction mechanisms occur in RyR2. Here, we combine microseconds of all-atom molecular dynamics (MD) simulations with mutagenesis and electrophysiology experiments to investigate large K+ conductance and charge selectivity (cation vs anion) in an open-state structure of RyR2. Our results show that a water-mediated knock-on mechanism enhances the cation permeation. The polar Q4863 ring may function as a confinement zone amplifying charge selectivity, while the cytoplasmic vestibule can contribute to the efficiency of the cation attraction. We also provide direct evidence that t...

Hypertension in Russia: Changes Observed After 4 Years of a Comprehensive Health System Improvement Program in the Yaroslavl Region.

Abstract: Rates of cardiovascular mortality and morbidity in Russia have been among the highest in Europe. A comprehensive health system improvement program targeting better diagnosis and control of hypertension was undertaken in the Yaroslavl Region of Russia. This initiative was a joint program between clinicians, the Department of Health and Pharmacy of the Yaroslavl Region, and Novartis Pharma LLC. From 2011 to 2014, the blood pressure control rate improved substantially (94% relative improvement), the percentage of patients with a systolic blood pressure ≥180 mm Hg decreased (from 10% to 5%), and there was a reduction in stroke incidence rate from 4.6 to 3.7 per 1000 population. During this same period, significant changes were made to the way hypertension was diagnosed and treated across all regional government polyclinics, and the use of antihypertensive therapies increased.

Inaugural Maximum Values for Sodium in Processed Food Products in the Americas

Abstract: Reducing dietary salt/sodium is one of the most cost-effective interventions to improve population health. There are five initiatives in the Americas that independently developed targets for reformulating foods to reduce salt/sodium content. Applying selection criteria, recommended by the Pan American Health Organization (PAHO)/World Health Organization (WHO) Technical Advisory Group on Dietary Salt/Sodium Reduction, a consortium of governments, civil society, and food companies (the Salt Smart Consortium) agreed to an inaugural set of regional maximum targets (upper limits) for salt/sodium levels for 11 food categories, to be achieved by December 2016. Ultimately, to substantively reduce dietary salt across whole populations, targets will be needed for the majority of processed and pre-prepared foods. Cardiovascular and hypertension organizations are encouraged to utilize the regional targets in advocacy and in monitoring and evaluation of progress by the food industry.

CPVT-associated cardiac ryanodine receptor mutation G357S with reduced penetrance impairs Ca2+ release termination and diminishes protein expression.

Abstract: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the most lethal inherited cardiac arrhythmias mostly linked to cardiac ryanodine receptor (RyR2) mutations with high disease penetrance. Interestingly, a novel RyR2 mutation G357S discovered in a large family of more than 1400 individuals has reduced penetrance. The molecular basis for the incomplete disease penetrance in this family is unknown. To gain insights into the variable disease expression in this family, we determined the impact of the G357S mutation on RyR2 function and expression. We assessed spontaneous Ca2+ release in HEK293 cells expressing RyR2 wildtype and the G357S mutant during store Ca2+ overload, also known as store overload induced Ca2+ release (SOICR). We found that the G357S mutation reduced the percentage of RyR2-expressing cells that showed SOICR. However, in cells that displayed SOICR, G357S reduced the thresholds for the activation and termination of SOICR. Furthermore, G357S decreased the thermal stability of the N-terminal domain of RyR2, and markedly reduced the protein expression of the full-length RyR2. On the other hand, the G357S mutation did not alter the Ca2+ activation of [3H]ryanodine binding or the Ca2+ induced release of Ca2+ from the intracellular stores in HEK293 cells. These data indicate that the CPVT-associated G357S mutation enhances the arrhythmogenic SOICR and reduces RyR2 protein expression, which may be attributable to the incomplete penetrance of CPVT in this family.

Frequency and Outcomes of Postrandomization Atrial Tachyarrhythmias in the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial

Abstract: Background— Whether adding cardiac resynchronization therapy (CRT-D) to an implanted cardioverter–defibrillator alters the risk of atrial fibrillation or other atrial tachyarrhythmias (AF/AT), or if postimplantation AF/AT modulate the benefits of CRT-D, remain unknown. Methods and Results— We studied 972 Resynchronization/Defibrillation in Ambulatory Heart Failure Trial (RAFT) participants without permanent AF, who were randomized to CRT-D (n=495) versus nonresynchronization defibrillator (implanted cardioverter–defibrillator; n=477) within the predefined stratum eligible for an atrial lead. Occurrence of postrandomization AF/AT was prospectively assessed, and Cox models were used to test the independent association between the postrandomization AF/AT and the RAFT primary composite outcome of all-cause mortality or hospitalization for heart failure. Over 41 (±19) months, postrandomization AF/AT occurred in 216 (45.3%) patients randomized to implanted cardioverter–defibrillator and 249 (50.3%) randomized to CRT-D. After adjusting for competing risk of death, randomization to CRT-D increased risk of postrandomization AF/AT (hazard ratio, 1.20; 95% confidence interval, 1.00–1.42; P =0.045). Postrandomization AF/AT, which remained paroxysmal in 69.5%, did not reduce biventricular pacing percentage. In adjusted models, postrandomization AF/AT was not associated with the primary outcome (hazard ratio, 1.04; 95% confidence interval, 0.84–1.30). However, AF/AT was associated with a borderline decreased risk of mortality (hazard ratio, 0.75; 95% confidence interval, 0.58–1.00) but increased risk of heart failure hospitalization (hazard ratio, 1.43; 95% confidence interval, 1.08–1.90). Conclusions— In RAFT, nearly half of the patients developed postrandomization AF/AT, and those randomized to CRT-D had borderline significant higher risk. Postrandomization AF/AT was associated with risk of heart failure hospitalization, but not with the primary composite outcome. Clinical Trial Registration— URL: . Unique identifier: [NCT00251251][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00251251&atom=%2Fcircae%2F9%2F5%2Fe003807.atom