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.

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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.

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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.

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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.

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Sex Differences in Forearm Vasoconstrictor Response to Voluntary Apnea

Is there a difference in how men and women respond to apnea? Yes, according to the recent work by Patel et al published as part of a special call for papers on “Sex and Gender Differences in Cardiovascular Physiology” in AJP-Heart and Circ. Listen as Guest Editor Virginia Miller leads an engaging conversation with lead author Matthew Muller (Penn State Hershey Heart and Vascular Institute) and expert Nina Stachenfeld (The John B. Pierce Laboratory) about the sex differences noted between young men and young women in response to a sympathetic stressor, as well as the roles of aging and reproductive hormones in the noted sex differences.

Hardikkumar M. Patel , Matthew J. Heffernan , Amanda J. Ross, Matthew D. Muller Sex differences in forearm vasoconstrictor response to voluntary apnea Am J Physiol Heart Circ Physiol, published December 6, 2013, doi: 10.1152/ajpheart.00746.2013.

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Smoking and Sympathetic Nerve Activity in Women

Does increased sympathetic nerve activity put women smokers at greater risk for heart attacks? Yes, according to a new study by Middlekauff and colleagues published recently in AJP-Heart and Circ. In this podcast Associate Editor Irving Zucker interviews senior author Holly Middlekauff (University of California-Los Angeles) and leading expert Vaughan Macefield (University of Western Sydney) about this insightful work which explores how baroreflex control of sympathetic nerve activity is impaired in women smokers. Listen as we explore how normal sympathetic nerve activity fluctuations associated with menstrual cycle hormonal changes in premenopausal women are altered by smoking, as well as second-hand smoke, and chronic smoke inhalation.

Holly R. Middlekauff, Jeanie Park, Harsh Agrawal, Jeffrey A. Gornbein Abnormal sympathetic nerve activity in women exposed to cigarette smoke: a potential mechanism to explain increased cardiac risk Am J Physiol Heart Circ Physiol, published November 15, 2013, doi: 10.1152/ajpheart.00502.2013.

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Human Aspirate - Native Coronary Arteries Versus Vein Grafts

Just two weeks after this podcast was originally recorded, our Editor in Chief Dr. William C. Stanley passed away unexpectedly. We are all tremendously saddened by this loss, but feel that presenting this podcast—the last one recorded with Dr. Stanley—honors his work in the journal, in particular his innovative podcast series. In this podcast Dr. Stanley interviewed author Petra Kleinbongard (University of Essen Medical School) and leading expert William Chilian (Northeast Ohio Medical University) about the work by Kleinbongard and colleagues comparing downstream human coronary aspirate and soluble substances after stent procedures in patients with native coronary arteries and those who had previously undergone revascularization with a saphenous vein graft. Is the potential for microvascular obstruction the same for both sets of patients? Listen as the experts weigh in on this elegant study which examines the pathophysiological consequences of stenting.

Petra Kleinbongard, Theodor Baars, Stefan Moehlenkamp, Philipp Kahlert, Raimund Erbel, Gerd Heusch Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris Am J Physiol Heart Circ Physiol, published online October 15, 2013, DOI: 10.1152/ajpheart.00358.2013.

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3D Printing Physiology Laboratory Technology

Is 3D printing an attainable reality or a futuristic ideal? In their recently published Perspective, Sulkin et al argue that small-scale instrumentation manufacturing in plastic from a 3D desktop printer is not only here and now, but also affordable. Listen to our lively and engaging podcast as Consulting Editor Dr. Steven P. Jones interviews senior author Dr. Igor Efimov (Washington University in St. Louis) and leading expert Dr. Hee Cheol Cho (Cedars-Sinai Heart Institute) about ancient printing techniques, the inherent tinkering work methods of physiologists, open source design software programs, and surprisingly low-cost printing technology. Is a 3D desktop printer the future of cardiovascular research labs everywhere? Listen and find out.

Matthew S. Sulkin, Emily Widder, Connie C. Shao, Katherine M. Holzem, Christopher Gloschat, Sarah R. Gutbrod, Igor R. Efimov 3D Printing Physiology Laboratory Technology Am J Physiol Heart Circ Physiol, published online September 16, 2013, DOI: 10.1152/ajpheart.00599.2013.

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p90 Ribosomal S6 Kinase 3 and Interstitial Fibrosis

What is RSK3 and how can it help us uncover the underlying mechanisms of hypertrophic cardiomyopathy? Associate Editor Meredith Bond leads an engaging conversation between senior author Michael Kapiloff (University of Miami) and leading expert Nikolaos Frangogiannis (Albert Einstein College of Medicine) about the exciting new study by Passariello et al. Listen as we explore the clinical implications of targeting RSK3 as a crucial pathway in the pathogenesis of fibrosis. How can we translate the understanding of the mechanisms of RSK3 and its effect on cardiomyocytes and fibroblasts to targeted drug therapies for the nearly 5 million Americans—both children and adults—afflicted with left ventricular hypertrophy every year? Listen and learn more.

Catherine L. Passariello , Marjorie Gayanilo , Michael D. Kritzer , Hrishikesh Thakur , Zoharit Cozacov , Francesca Rusconi , David Wieczorek , Michael Sanders , Jinliang Li, Michael S. Kapiloff p90 ribosomal S6 kinase 3 contributes to cardiac insufficiency in α-tropomyosin Glu180Gly transgenic mice Am J Physiol Heart Circ Physiol, published online August 2, 2013, doi: 10.1152/ajpheart.00237.2013.

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Late Sodium Current Inhibition Slows the Progression to Heart Failure

Can early inhibition of the late sodium current slow hypertension-induced t-tubule disruption and calcium cycling defects that lead to heart failure? Join Editor in Chief William C. Stanley as he explores the innovative work by Aistrup et al with senior author J. Andrew Wasserstrom (Northwestern University Feinberg School of Medicine) and leading expert Guy Salama (University of Pittsburgh). Listen as they discuss the effects of chronic treatment with ranolazine on T-tube disruption and the development of heart failure.

Gary L. Aistrup, Deepak K. Gupta, James E. Kelly, Matthew J. O'Toole, Amanda Nahhas, Nimi Chirayil, Sol Misener, Lauren Beussink, Neha Singh, Jason Ng, Mahendra Reddy, Thitipong Mongkolrattanothai, Nesrine El-Bizri, Sridharan Rajamani, John C. Shryock, Luiz Belardinelli, Sanjiv J. Shah, J. Andrew Wasserstrom Inhibition of the late sodium current slows t-tubule disruption during the progression of hypertensive heart disease in the rat Am J Physiol Heart Circ Physiol, published online July 19, 2013, doi: 10.1152/ajpheart.00401.2013.

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