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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