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


Acylcarnitines in Human Heart Failure

What role do circulating acylcarnitines play in the heart failure metabolome? Listen as Guest Editor Sumanth Prabhu (University of Alabama at Birmingham) interviews lead author and Associate Editor Christine Des Rosiers (Universite de Montreal, Montreal Heart Institute), first author Matthieu Ruiz (Universite de Montreal, Montreal Heart Institute), and renowned content expert Heinrich Taegtmeyer (University of Texas Medical School), about the intriguing new study analyzing fatty acid metabolic perturbations in patients with heart failure with reduced ejection fraction (HFrEF). Des Rosiers and co-authors began their investigations over 10 years ago, and through persistence and new mass spectrometry analytical technologies, pursued a novel mechanism “contributing to the global lipid perturbation in human heart failure.” The work by Ruiz et al was published in the AJP-Heart and Circ Call for Papers on Heart Failure: Novel Therapeutic Pathways Emerging from Basic Science. This special extended podcast discusses the innovative techniques utilized by Des Rosiers, Ruiz and colleagues, along with the passion and tenacity required to understand the alterations in heart failure in long-chain fatty acid metabolism in heterogenous HFrEF patient cohorts. Did the authors find correlations to cardiac structural parameters, along with links between very long chain acylcarnitines and arrhythmias? Listen and learn.


Matthieu Ruiz, Francois Labarthe, Annik Fortier, Bertrand Bouchard, Julie Thompson Legault, Virginie Bolduc, Odile Rigal, Jane Chen, Anique Ducharme, Peter A Crawford, Jean-Claude Tardif, Christine Des Rosiers Circulating Acylcarnitine Profile in Human Heart Failure: A Surrogate of Fatty Acid Metabolic Dysregulation in Mitochondria and Beyond Am J Physiol Heart Circ Physiol, published July 14, 2017. DOI: 10.1152/ajpheart.00820.2016


Cardio-postural Blood Pressure Control

How do the cardiac baroreflex and muscle pump systems work together to maintain blood pressure when you are standing? Listen as Associate Editor Robert Hester interviews authors Kouhyar Tavakolian (University of North Dakota) and Andrew Blaber (Simon Fraser University), along with content expert Jerry Collins (Alabama A & M University) about the innovative study by Xu et al. The authors explored the direct neural component between the brain and the muscle pump to help maintain blood pressure during a sit-to-stand transition, as well as a simple standing posture. Employing state-of-the-art analytics such as the wavelet transform coherence method and the convergent cross-mapping method, the authors simultaneously monitored the interrelationships between the human subjects’ cardiovascular, musculoskeletal, and balance systems. While the current study investigated young, healthy subjects, are there future implications for helping stroke patients, the elderly, or concussion injury patients? Listen and learn more.


Da Xu, Ajay Verma, Amanmeet Garg, Michelle Bruner, Reza Fazel-Rezai, Andrew P. Blaber, Kouhyar Tavakolian Significant role of the cardio-postural interaction in blood pressure regulation during standing Am J Physiol Heart Circ Physiol, published September 5, 2017. DOI: 10.1152/ajpheart.00836.2016


Folic Acid and Exercise Hyperemia in Aging

What are the effects of folic acid on exercise-induced increases in blood flow in healthy older adults? Listen as Associate Editor Nancy Kanagy (University of New Mexico School of Medicine) interviews first author Steven Romero (UT Southwestern Medical Center) and content expert Thomas Barstow (Kansas State University) about the clinical translational study by Romero and co-authors investigating the role of folic acid in mitigating some of the profound changes in arterial vasculature and malperfusion of active skeletal muscle with aging. This innovative study is part of the AJP-Heart and Circulatory Physiology Call for Papers on Mining Natural Products for Cardiovascular Benefits. Is folic acid as a dietary supplement beneficial in preserving exercise capacity in older adults? This may bring new meaning to the adage “eat your spinach,” if doing so ameliorates the loss of nitric oxide in aging. Listen and learn more.


Steven A. Romero, Daniel Gagnon, Amy N Adams, Gilbert Moralez, Ken Kouda, Manall F Jaffery, Matthew N. Cramer, Craig G. Crandall Folic Acid Ingestion Improves Skeletal Muscle Blood Flow during Graded Handgrip and Plantar Flexion Exercise in Aged Humans Am J Physiol Heart Circ Physiol, published June 30, 2017. DOI: 10.1152/ajpheart.00234.2017


Hypoxia Inducible Factor-alpha and Cancer Cachexia

How does cancer cachexia directly affect the heart? Listen as Deputy Editor Merry Lindsey (University of Mississippi Medical Center) tackles this question and more as she interviews lead author Loren Wold (The Ohio State University) and content expert Hemal Patel (VA San Diego Healthcare System, University of California San Diego) about the insightful study by Devine et al on cancer-induced cachexia and its effects on cardiac muscle structure and physiology. Using a proteomics approach, Wold and colleagues investigated how hypoxia inducible factor-1alpha served as a sensor for oxygen handling in the heart during cancer cachexia, a global hypoxic event. What strain and sex -dependent effects of tumor formation did Wold and co-authors observe in their model of cancer cachexia? Why was it significant that c-kit was elevated in the left ventricle of the tumor-bearing mice? Does lipid accumulation in the cachexia model bear resemblance to accelerated aging? Many questions, many answers. Listen now.


Raymond D. Devine, Sabahattin Bicer, Peter J. Reiser, Loren E. Wold Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice Am J Physiol Heart Circ Physiol, published June 1, 2017. DOI: 10.1152/ajpheart.00090.2016


nNOS and Coronary Flow During Mental Stress

What is the mechanism by which mental stress affects cardiac performance? Listen as Associate Editor Fabio Recchia (Temple University Lewis Katz School of Medicine, and Scuola Superiore Sant'Anna, Pisa, Italy) interviews lead author, and fellow Associate Editor, Ajay Shah (King’s College London) along with content expert Nazareno Paolocci (Johns Hopkins University) about the clinical translational work by Khan et al. Shah and co-authors explored for the first time the effects of mental stress elicited by the Stroop color-word test and coronary flow and diameter on patients undergoing elective diagnostic coronary catheterization. The key finding is that neuronal nitric oxide synthase (nNOS), in additional to endothelial nitric oxide synthase (eNOS), contributes to the local regulation of coronary flow in response to mental stress. The authors showed that the Stroop test stimulated nNOS without altering heart rate and blood pressure. Does this indicate specific stimulation of the perivascular nerves? Listen now to this intriguing podcast exploring cross-talk between the brain and heart.


Sitara Gulurkh Khan, Narbeh Melikian, Husain Shabeeh, Ana Rita Cabaco, Katherine Martin, Faisal Khan, Kevin O'Gallagher, Phil Chowienczyk, Ajay M. Shah The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase Am J Physiol Heart Circ Physiol, published June 23, 2017. DOI: 10.1152/ajpheart.00745.2016


EET Intervention on Wnt1, NOV and HO-1 Signaling Prevents Obesity-Induced Cardiomyopathy

Do the well-established beneficial effects of EETs (epoxyeicosatrienoic acids) in the vasculature also extend to the myocardium? That's just what we explore in this new podcast about the work by Cao et al, which is highlighted in our Call for Papers on Heart Failure - Novel Therapeutic Pathways Emerging from Basic Science. Listen as Consulting Editor David D. Gutterman (Medical College of Wisconsin) interviews lead author Nader G. Abraham (New York Medical College) and content expert Kevin Dellsperger (Augusta University Health System) about the translational work by Abraham and colleagues. As a downregulator of NOV, EETs act as anti-inflammatory molecules attenuating cardiac damage. Abraham and co-authors found that EETs increase Wnt, resulting in the reprogramming of epicardial fat toward a brown fat phenotype, thereby increasing left ventricle function and contractility. What novel and "potentially drug-able" pathway is responsible for attenuating obesity-induced cardiomyopathy? Listen now.


Jian Cao, Shailendra P. Singh, John McClung, Gregory Joseph, Luca Vanella, Ignazio Barbagallo, Houli Jiang, John R. Falck, Michael Arad, Joseph I. Shapiro, Nader G. Abraham EET Intervention on Wnt1, NOV and HO-1 Signaling Prevents Obesity-Induced Cardiomyopathy in Obese Mice Am J Physiol Heart Circ Physiol, published June 2, 2017. DOI: 10.1152/ajpheart.00093.2017


Leucine Metabolism Inhibits Cardiac Glucose Uptake

Does the branch chain amino acid leucine mediate cardiac insulin resistance? Listen as Associate Editor Gary Lopaschuk (University of Alberta) interviews lead author Luc Bertrand (Université Catholique de Louvain) and content expert Ravichandran Ramasamy (NYU Langone Medical Center) about the recent work by Renguet et al which investigated whether leucine is simply a biomarker of type 2 diabetes or a factor of the metabolic inflexibility which is a hallmark of type 2 diabetes pathogenesis. Bertrand and colleagues showed that the inhibitory reaction of leucine and ketone bodies in glucose transport requires an increase in protein acetylation, which then contributes to the inhibition of cardiac glucose uptake by hampering the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. This new study by Bertrand and colleagues may be “a new piece in the complex puzzle of cardiac insulin resistance.” Listen and learn more.


Edith Renguet, Audrey Ginion, Roselle Gélinas, Laurent Bultot, Julien Auquier, Isabelle Robillard Frayne, Caroline Daneault, Jean-Louis Vanoverschelde, Christine Des Rosiers, Louis Hue, Sandrine Horman, Christophe Beauloye, Luc Bertrand Metabolism and acetylation contribute to leucine-mediated inhibition of cardiac glucose uptake Am J Physiol Heart Circ Physiol, published online June 23, 2017. DOI: 10.1152/ajpheart.00738.2016


β-AR Stimulation and Alternans in Border Zone Cardiomyocytes

Are calcium alternans in the post-MI border zone more susceptible to the effects of sympathetic stimulation than in normal zone cardiomyocytes? In this podcast Consulting Editor Crystal Ripplinger uncovers the answer in her interview with lead author Jordi Heijman and content expert Thomas Hund about the recent work by Tomek et al. Heijman and co-authors explored sympathetic stimulation and its role in arrhythmogenesis by applying an innovative computational model to the canine post-MI border zone. Did Heijman and colleagues find that β-adrenergic stimulation suppressed alternans by one single mechanism or via multiple pathways? Did Heijman and co-authors also find that hyperinnervation in the border zone is actually anti-arrhythmic, by preventing alternans? Listen and find out.


Jakub Tomek, Blanca Rodriguez, Gil Bub, Jordi Heijman β-adrenergic receptor stimulation inhibits proarrhythmic alternans in post-infarction border zone cardiomyocytes: a computational analysis Am J Physiol Heart Circ Physiol, published online May 26, 2017. DOI: 10.1152/ajpheart.00094.2017


Resveratrol and Exercise Capacity in Heart Failure

Does resveratrol positively impact exercise intolerance in heart failure patients? Listen as Associate Editor Christine Des Rosiers (Universite de Montreal) interviews lead author Jason Dyck (University of Alberta) and content expert Yan Burelle (University of Ottawa) about the exciting new study by Sung et al, which used a mouse model of heart failure to determine if treatment with resveratrol restored exercise tolerance to normal levels. Dyck and co-authors clearly show that resveratrol is effective as a treatment for exercise intolerance in heart failure, not solely as a preventative strategy, and this may have important clinical implications for human heart failure patients. What role does the gut microbiome play in this resveratrol treatment study, and what cautionary words do these experts have about equating nutraceutical resveratrol treatment with the naturally occurring polyphenol resveratrol commonly found in red wine? Listen and find out.


Miranda M. Sung, Nikole J Byrne, Ian M Robertson, Ty T Kim, Victor Samokhvalov, Jody Levasseur, Carrie-Lynn M Soltys, David Fung, Neil Tyreman, Emmanuel Denou, Kelvin Jones, John M Seubert, Jonathan D. Schertzer, Jason R.B. Dyck Resveratrol improves exercise performance and skeletal muscle oxidative capacity in heart failure Am J Physiol Heart Circ Physiol, published April 1, 2017. DOI: 10.1152/ajpheart.00455.2016