Search

Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac function. To dissect the regulatory network of cardiac Ca(2+) handling, we performed a chemical suppressor screen on zebrafish tremblor embryos, which suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent activity to restore coordinated contractions in tremblor. We show that efsevin binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the transfer of Ca(2+) from intracellular stores into mitochondria. In cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+) sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and irregular contractions. We further show that overexpression of VDAC2 recapitulates the suppressive effect of efsevin on tremblor embryos whereas VDAC2 deficiency attenuates efsevin's rescue effect and that VDAC2 functions synergistically with MCU to suppress cardiac fibrillation in tremblor. Together, these findings demonstrate a critical modulatory role for VDAC2-dependent mitochondrial Ca(2+) uptake in the regulation of cardiac rhythmicity.

The article examines the regulatory network of cardiac Ca2+ handling through the creation of a chemical suppressor screen on zebrafish tremblor embryos. Topics discussed include the identification of efsevin based on its ability to restore coordinated contractions in tremblor and its capacity to bind to VDAC2 which in turn allows mitochondrial Ca2+ uptake and transfer acceleration from intracellular stores into mitochondria.

The University of British Columbia medical school relies mostly on lectures and problem based learning tutorials (PBL) in the first two years of its undergraduate medical program. While PBL exposes students to clinical scenarios, most students do not acquire experience with patients until their clerkships in 3rd and 4th year. Introduction of PBL starting in 1997 resulted in curtailment of some aspects of the former curriculum, notably basic and clinical pharmacology. Graduating medical students across Canada recognize this deficiency. Canadian medical schools make an abrupt transition between the classroom-based years and clerkship years. The shift from classroom to bedside is often difficult for students. By 2nd year many students are weary of PBL and eager to be part of a medical team, while in 3rd year many students find the change of learning environment extremely stressful. We felt that short educational videos could help bridge this transition, by exposing first and second year students to the stories of real patients, told in their own words. During summer 2010, 30 videos were prepared by 9 undergraduate medical students, under the direction of Dr. Thomas Perry (Internal Medicine and Clinical Pharmacology). The videos are edited from patient interviews and physical examinations. The videos range from 2-7 minutes in length, and demonstrate: *common and classical (but uncommon) conditions (e.g. diabetes, adrenal failure) *the use of drugs to solve clinical problems (e.g. intravenous opioids for acute pain) *pathophysiologically important medical phenomena (e.g. idiopathic orthostatic hypotension, symptoms of adrenal insufficiency) *the importance of the doctor-patient relationship (e.g. a man dying of metastatic lung cancer who experienced neglectful treatment) *routine hospital procedures (eg. the process of converting a urine sample into useful information) Many of the videos are currently being introduced across the first two years of the undergraduate curriculum, particularly during "PBL case wrap-up" lectures to illustrate how the principles learned from the week's PBL case can be applied to similar cases in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Left ventricular (LV) mass is a well-established prognostic indicator for cardiovascular risk. Measurement of LV mass on coronary computed tomography angiography (CCTA) is considered optional. We aimed to assess for associations between LV mass measured on CCTA with all-cause mortality (ACM) risk and to determine age- and sex-specific distributions., Methods: We evaluated patients without known coronary artery disease (CAD) who underwent CCTA at a single center. We assessed age- and sex-specific distributions (10th, 25th, 50th, 75th, and 90th percentiles) of LV mass index. ACM, the primary endpoint, was recorded over a median period of 5.1 [interquartile range: 1.4-8.4] years. The association between LV mass and mortality risk was assessed using multivariable Cox models adjusted for age, sex, medical history, coronary artery calcium (CAC) score and CCTA stenosis., Results: 4187 patients (mean age: 61.9 ​± ​11.7, 63 ​% male) were included. Male sex, African American ethnicity, Hypertension, CAC>400, and smoking were independent predictors of increased LV mass index. During the median 5.1 years of study follow, 265 (6.3 ​%) deaths occurred. Increased LV mass index percentiles were associated with increased risk of ACM. The addition of LV mass index percentiles improved discrimination and reclassification for mortality prediction over a model with age, sex, conventional risk factors, CAC score and CCTA stenosis severity (X 2 improvement: 22.68, NRI: 28 ​%, both p ​< ​0.001)., Conclusion: In a large sample of patients without known CAD who underwent CCTA, increased LV mass index provided independent and incremental prognostic value for all-cause mortality. Assessment of LV mass by CCTA, considering age and gender distribution, can be utilized clinically to identify patients with high myocardial mass., Competing Interests: Declaration of competing interest All authors declare no relevant conflicts of interest related to the study., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: In patients with atrial fibrillation, incomplete left atrial appendage (LAA) closure is associated with an increased risk for cardio-embolic events compared to complete closure. In this study, we aimed to determine the prevalence and risk factors for incomplete surgical closure of the LAA in the modern surgical era., Methods: Records of 74 patients with surgical LAA closure who underwent follow-up transesophageal echocardiogram for any reason between 2010 and 2016, were assessed for incomplete closure. Complete closure was defined by absence of Doppler or color flow between the left atrial appendage and the left atrial body in more than 2 orthogonal views., Results: Surgical LAA closure was incomplete in 21 patients (28%) and complete in 53 patients (72%). All included cases were completed via oversewing method with a double layer of running suture with or without excision of the LAA. While no individual demographic, echocardiographic, or surgical feature was significantly different between groups, incomplete closure of the LAA was more prevalent in patients with two or more of the risk factors; female sex, hypertension, and hyperlipidemia (OR 5.1, 95%Cl 1.5-17)., Conclusions: A significant rate of incomplete surgical LAA closure still exists in the modern surgical era, and the presence of multiple risk factors associate an increased risk of incomplete closure.