Treadmill BP in Simulated Peripheral Artery Disease

What is driving the exaggerated blood pressure response to exercise in patients with peripheral arterial disease (PAD)? In this podcast, Editor in Chief Irving H. Zucker (University of Nebraska Medical Center) interviews senior author Gail Thomas (Penn State College of Medicine) and content expert Hanjun Wang (University of Nebraska Medical Center) about the unique study by Kuczmarski et al. Thomas and co-authors used telemetry to record blood pressure during exercise in conscious animals, both before and after bi-lateral femoral artery ligation. The studied was conducted over a period of two months, a technical success given that the authors used chronically-instrumented conscious animals. Thomas and collaborators found that the blood pressure response was exaggerated as early as 3 days after femoral artery ligation and lasted for the duration of the experiment in both female and male mice. Are the mechanisms that play a role in blood pressure response to short-term ligation, such as cytokines IL-6 and activation of the purinergic P2X3 receptors, also at work here? Listen and find out.

 

J. Matthew Kuczmarski, Kellee Unrath, Gail D. Thomas Exaggerated cardiovascular responses to treadmill running in rats with peripheral arterial insufficiency Am J Physiol Heart Circ Physiol, published October 6, 2017. DOI: 10.1152/ajpheart.00401.2017

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Calcium Regulation in E99K Mouse Heart

What is the role of calcium transients in sudden cardiac death associated with hypertrophic cardiomyopathy? Listen as Associate Editor Gary Lopaschuk (University of Alberta) interviews lead author Steven Marston (Imperial College London) and content expert Susan Howlett (Dalhousie University) about the work by Marston and colleagues, who studied alterations in calcium handling in a unique transgenic mouse model of hypertrophic cardiomyopathy, a common form of cardiac hypertrophy. Analyzing both calcium waves and calcium sparks, Marston and co-authors found that the proportion of transgenic mice which had a higher spark mass did succumb to sudden cardiac death at 40 days old. In comparison, older transgenic mice and younger non-transgenic mice with a lower spark mass did not die of sudden cardiac death. Given that the transgenic mice showed spontaneous calcium release and more frequent calcium sparks, did the authors find these mice had a higher incidence of arrhythmias? Does the strain of mice used in the transgenic model have implications on study results? Listen to find out.

 

Christina Rowlands, Thomas Owen, Saheed Lawal, Shuangyi Cao, Samata Pandey, Hsiang-Yu Yang, Weihua Song, Ross Wilkinson, Anita Alvarez-Laviada, Katja Gehmlich, Steven Marston, Kenneth T. MacLeod Circulating Age and strain related aberrant Ca2+ release is associated with sudden cardiac death in the ACTC E99K mouse model of hypertrophic cardiomyopathy Am J Physiol Heart Circ Physiol, published September 8, 2017. DOI: 10.1152/ajpheart.00244.2017

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CaMKII-Dependent Regulation of Atrial Late Sodium Current and Excitability

What is the interplay between late sodium current and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the early stages of atrial fibrillation induced by abnormal focal activity? Listen as Consulting Editor Igor Efimov (George Washington University) interviews lead author Thomas Hund (The Ohio State University) and content expert Patrick Boyle (Johns Hopkins University) about the unique modeling study by Onal et al. Hund and co-authors created a model focused on the CaMKII signaling pathway, itself dramatically altered in patients with atrial fibrillation, to piece together the sequence of events and mechanisms which trigger atrial arrhythmias. Hund and collaborators became interested in how CaM kinase II regulates the voltage-gated sodium channel, and their model allows for the cell to respond to various stimuli. Listen as our experts discuss how cell models portend the future of tissue-scale modeling (including a reference to the movie Jaws) and the necessity of balancing layers of complexity with the need for simplicity to maintain the integrity of the model.

 

Birce Onal, Daniel Gratz, Thomas J Hund Ca2+/calmodulin kinase II-dependent regulation of atrial myocyte late Na+ current, Ca2+ cycling and excitability: a mathematical modeling study Am J Physiol Heart Circ Physiol, published August 25, 2017. DOI: 10.1152/ajpheart.00185.2017

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