AJP-Heart and Circulatory Physiology Podcast

JAPANESE VERSION: Rapid Electrical Stimulation and Intercellular Proteins

Following the introduction in English, this podcast interview is presented in Japanese. It is well known that rapid pacing of the heart causes calcium overload and myocardial cell damage in heart failure patients. However, the cellular mechanisms underlying this phenomenon are unknown. Listen as Associate Editor Masafumi Kitakaze interviews lead author Tomoko Ohkusa (Yamaguchi University Graduate School of Medicine) and expert Motoaki Sano (Keio University School of Medicine) about the latest work by Nakashima et al, which explores rapid electrical stimulation and adhesion gap junctions in cardiomyocytes. Does beta-Catenin play an important role in the formation and stability of gap junctions? Could beta-Catenin signaling pathways form the basis of new cellular therapies to modulate intracellular junction remodeling? Listen to find out.

Tadamitsu Nakashima, Tomoko Ohkusa, Yoko Okamoto, Masaaki Yoshida, Jong-Kook Lee, Yoichi Mizukami, Masafumi Yano Rapid electrical stimulation causes alterations in cardiac intercellular junction proteins of cardiomyocytes Am J Physiol Heart Circ Physiol, published online Articles in Press March 7, 2014; published in May 1, 2014 issue. DOI: 10.1152/ajpheart.00653.2013.

ENGLISH VERSION: Rapid Electrical Stimulation and Intercellular Proteins

It is well known that rapid pacing of the heart causes calcium overload and myocardial cell damage in heart failure patients. However, the cellular mechanisms underlying this phenomenon are unknown. Listen as Associate Editor Masafumi Kitakaze interviews lead author Tomoko Ohkusa (Yamaguchi University Graduate School of Medicine) and expert Motoaki Sano (Keio University School of Medicine) about the latest work by Nakashima et al, which explores rapid electrical stimulation and adhesion gap junctions in cardiomyocytes. Does beta-Catenin play an important role in the formation and stability of gap junctions? Could beta-Catenin signaling pathways form the basis of new cellular therapies to modulate intracellular junction remodeling? Listen to find out.

Tadamitsu Nakashima, Tomoko Ohkusa, Yoko Okamoto, Masaaki Yoshida, Jong-Kook Lee, Yoichi Mizukami, Masafumi Yano Rapid electrical stimulation causes alterations in cardiac intercellular junction proteins of cardiomyocytes Am J Physiol Heart Circ Physiol, published online Articles in Press March 7, 2014; published in May 1, 2014 issue. DOI: 10.1152/ajpheart.00653.2013.

Aerobic Exercise Acutely Prevents Endothelial Dysfunction

Can exercise protect us from the deleterious effects of mental stress? Yes, according to new research by Sales et al. Listen as Associate Editor Nancy Kanagy interviews lead author Antonio Nobrega (Fluminense Federal University, Brazil) and expert David Poole (Kansas State University) about this fascinating new research into how just 40 minutes of exercise can prevent or reverse the loss of endothelial function due to mental stress in patients with metabolic syndrome. Should we all invest in a treadmill for the office? Listen and find out.

Allan R. K. Sales, Igor A. Fernandes, Natalia G. Rocha, Lucas S. Costa, Helena N. M. Rocha, Joao D. M. Mattos, Lauro C. Vianna, Bruno M. Silva, Antonio C. L. Nobrega Aerobic exercise acutely prevents the endothelial dysfunction induced by mental stress among subjects with metabolic syndrome: the role of shear rate Am J Physiol Heart Circ Physiol, published online February 15, 2014. DOI: 10.1152/ajpheart.00811.2013.

Oxidative Stress and Cutaneous Local Heating in Young Smokers

We know smoking is bad for us, but can endothelial dysfunction in smokers be repaired, or even restored? Listen as Editor in Chief Dr. Irving H. Zucker interviews lead author Christopher Minson (University of Oregon) and expert Lacy Alexander (The Pennsylvania State University) about the work by Minson and colleagues which used the skin as a model for microvascular changes in smokers, which can indicate dysfunction earlier on in the progression of disease than macrocirculatory changes. Is nitric oxide a major player in the skin’s vasodilator response to a local cutaneous heat stressor? Listen now.

Naoto Fujii, Vienna E. Brunt, Christopher Todd Minson Tempol improves cutaneous thermal hyperemia through increasing nitric oxide bioavailability in young smokers Am J Physiol Heart Circ Physiol, published online March 28, 2014. DOI: 10.1152/ajpheart.00886.2013.

Adverse Perinatal Environment Contributes to Altered Cardiac Development and Function

Why are in utero conditions so critical to cardiovascular health after birth? Listen as Associate Editor Ronglih Liao interviews lead author Loren Wold (Ohio State University) and expert Anne Knowlton (University of California, Davis) about the latest insightful work by Velten et al, which tests a “two-hit” hypothesis mouse model—inflammation followed by hyperoxia—to analyze how cardiac function is altered very early in life. Is Wold’s innovative work bringing the 18th century biologist Lamarck’s theory of inheritance of acquired characteristics front and center in 21st century cardiovascular physiology? Listen and find out.

Markus Velten, Matthew W. Gorr, Dane J. Youtz, Christina Velten, Lynette K. Rogers, Loren E Wold Adverse Perinatal Environment Contributes to Altered Cardiac Development and Function Am J Physiol Heart Circ Physiol, published online March 7, 2014. DOI: 10.1152/ajpheart.00056.2014.

AMPK and Peripheral Vascular Insufficiency

Is AMP kinase activation a potential therapy for patients with peripheral artery disease? Listen as Editor in Chief Irving Zucker interviews lead author Todd Kinsella (Rigel Pharmaceuticals, Inc.) and expert Michael Massett (Texas A & M University) about the interesting new work by Baltgalvis et al. In the quest to improve exercise intolerance that plagues the millions of patients suffering from peripheral artery disease, Kinsella and colleagues developed and tested a series of indirect AMPK activators for beneficial exercise adaptation in a mouse model of aging, inactivity, and obesity. Did Kinsella and colleagues find any effect of AMPK activators on the microvascular and muscle dysfunction associated with intermittent claudication? Listen and find out.

Kristen A. Baltgalvis, Kathy White, Wei Li, Mark D. Claypool, Wayne Lang, Raniel Alcantara, Baljit K. Singh, Annabelle M. Friera, John McLaughlin, Derek Hansen, Kelly McCaughey, Henry Nguyen, Ira J. Smith, Guillermo Godinez, Simon J. Shaw, Dane Goff, Rajinder Singh, Vadim Markovtsov, Tian-Qiang Sun, Yonchu Jenkins, Gerald Uy, Yingwu Li, Alison Pan, Tarikere Gururaja, David Lau, Gary Park, Yasumichi Hitoshi, Donald G. Payan, Todd M. Kinsella Exercise performance and peripheral vascular insufficiency improve with AMPK activation in high-fat diet-fed mice Am J Physiol Heart Circ Physiol, published online February 21, 2014. DOI: 10.1152/ajpheart.00839.2013.

Coronary Vascular Control by PDE5 and Endothelin

While vasodilators and vasoconstrictors have been studied for decades as individual components of coronary blood flow modulation, recent work by Dirk Duncker and colleagues takes a rarely-seen integrative physiological approach to elucidate the mechanisms of both systems in relationship to each other. Listen as Associate Editor Fabio Recchia (Temple University and Scuola Superiore S. Anna, Pisa) interviews lead author Dirk Duncker (Erasmus University Medical Center Rotterdam) and expert Gerd Heusch (Universitatsklinikum Essen) about the highly complex work by Zhou et al, in which studying a chronically instrumented, conscious and exercising large animal model leads to new insights into the role of PDE5 in coronary vascular control. Can we really drill down to a mechanistic level when starting with an integrative physiology whole animal model? Listen now.

Zhichao Zhou, Vincent J. de Beer, Shawn B. Bender, A. H. Jan Danser, Daphne Merkus, M. Harold Laughlin, Dirk J. Duncker Phosphodiesterase-5 activity exerts a coronary vasoconstrictor influence in awake swine that is mediated in part via an increase in endothelin production Am J Physiol Heart Circ Physiol, published online January 24, 2014. DOI: 10.1152/ajpheart.00331.2013.

Ethanol Exposure Alters Early Cardiac Function in the Looping Heart: a Mechanism for Congenital Heart Defects?

Could the eye-opening results that a single dose of ethanol causes late-stage congenital heart defects in an avian model of Fetal Alcohol Syndrome lead to human clinical guidelines? It may be too early to tell, but the work by Karunamuni et al strives to find out. Listen as Associate Editor Leon De Windt (Maastricht University) interviews lead author Michiko Watanabe (Case Western Reserve University) and expert Wolfram Zimmermann (University Medical Center Goettingen) about this unique study which meshes cardiovascular physiology and biomedical engineering techniques, such as Doppler OCT, in an avian model of embryonic heart development correlating to the first trimester of human pregnancy. Can this open model of cardiogenesis lead to new interventional pacing techniques or rescue agents, such as folate, to restore or repair cardiac function in the embryo? Listen and learn.

Ganga Karunamuni, Shi Gu, Yong Qiu Doughman, Lindsy M. Peterson, Katherine Mai, Quinn McHale, Michael W. Jenkins, Kersti K. Linask, Andrew M. Rollins, Michiko Watanabe Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects? Am J Physiol Heart Circ Physiol, published February 1, 2014, DOI: 10.1152/ajpheart.00600.2013.

MMP-2 is Localized to the Mitochondria-Associated Membrane of the Heart

Is matrix metalloproteinase MMP-2 in the mitochondria of cardiomyocytes, near the mitochondria, or both? “In order to figure out what this protease is doing, you need to know precisely where it is,” says Richard Schulz (University of Alberta), lead author of the recent study by Hughes et al. In this podcast, Associate Editor Merry Lindsey (University of Mississippi Medical Center) interviews Shulz and expert Francisco Villarreal (University of California-San Diego) about this fascinating new work bringing fresh insights into the pattern of MMP subcellular distribution. Find out what’s in the MMP inhibitor clinical trial pipeline, and get a bird’s eye view of how the MMP biology field is evolving. Listen now.

Bryan G. Hughes, Xiaohu Fan, Woo Jung Cho, Richard Schulz. MMP-2 is localized to the mitochondria-associated membrane of the heart Am J Physiol Heart Circ Physiol, published December 27, 2013, doi: 10.1152/ajpheart.00909.2013.

Release Kinetics of Circulating Cardiac Myosin Binding Protein-C Following Cardiac Injury

Researchers have long sought out early biomarkers of cardiac injury, and the new work by Kuster et al takes this search in an exciting new direction. Listen as Associate Editor Merry Lindsey (University of Mississippi Medical Center) interviews lead author Sakthivel Sadayappan (Loyola University Chicago) and expert Ying Ge (University of Wisconsin) about the recent discovery that cardiac muscle-specific myosin binding protein-C is an ultra-early biomarker of myocardial infarction. Will it be feasible to apply detection of myosin binging protein-C to a multi-marker regime, particularly in concert with cardiac troponins, in a clinical setting? Listen and learn.

Diederik Kuster, Adriana Cardenas-Ospina, Lawson Miller, Christoph Liebetrau, Christian Troidl, Holger M Nef, Helge Möllmann, Christian W Hamm, Karen S Pieper, Kenneth W Mahaffey, Neal S Kleiman, Bruno Daniel Stuyvers, A. J. Marian, Sakthivel Sadayappan Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury Am J Physiol Heart Circ Physiol, published December 13, 2013, DOI: 10.1152/ajpheart.00846.2013.