Chronic Vagal Nerve Stimulation in Stroke-Prone SHR

Can restoring parasympathetic nerve activity in patients with primary hypertension prevent cardiovascular end organ damage? In this podcast Associate Editor Debra Diz (Wake Forest University School of Medicine) interviews lead author Harald Stauss (University of Iowa) and content expert Douglas Martin (University of South Dakota) about the study by Chapleau et al. Referred to as a “a technological tour de force” that combined chronic vagal nerve stimulation, chronic telemetric blood pressure measurements, and in vivo imaging of the long posterior ciliary artery (LPCA) using the slit lamp approach to assess endothelial function, the authors found that endothelial function improved, without changes in blood pressure. Does this approach have the potential to interrupt the pathway between blood pressure and end organ damage, when lowering blood pressure could lead to adverse clinical ramifications in elderly fall risk patients, for example? Listen and learn.

Mark W. Chapleau, Diane L Rotella, John J Reho, Kamal Rahmouni, Harald M. Stauss Chronic Vagal Nerve Stimulation Prevents High-Salt Diet-Induced Endothelial Dysfunction and Aortic Stiffening in Stroke-Prone Spontaneously Hypertensive Rats Am J Physiol Heart Circ Physiol, published May 20, 2016. DOI: 10.1152/ajpheart.00043.2016


Hypothermia/Rewarming Disrupts E-C Coupling

What is the connection between Tromso, Norway, hypothermia, rewarming, heart failure…and AJP-Heart and Circ? Listen to this fascinating new podcast as Associate Editor Leon De Windt (Cardiovascular Research Institute Maastricht) interviews lead author Gary Sieck (Mayo Clinic) and content expert Jolanda van der Velden (VU University Medical Center Amsterdam) about the intriguing and entirely unique work by Schaible at al, which explores how to protect the heart during rewarming after hypothermia. Whatever the cause of hypothermia—falling into a fjord, skiing accident—inadequate rewarming at a trauma center and/or restarting the heart in the field by first responders can both lead to heart failure. Listen as we discuss how hypothermia can inhibit the SERCA pump, as well as affect the sodium-calcium exchanger, slowing the clearance of calcium. Is it possible for a hypothermic person in asystole, if CPR is administered to restore circulation, to later be rewarmed and survive without any deficits or long-term side effects? Listen and find out.

Niccole Schaible, Young Soo Han, Thuy Hoang, Grace Arteaga, Torkjel Tveita, Gary Sieck Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes Am J Physiol Heart Circ Physiol, published June 1, 2016. DOI: 10.1152/ajpheart.00840.2015


Purinergic Dysregulation in Pulmonary Hypertension

What role do circulating nucleotides play in the pathobiology of pulmonary arterial hypertension (PAH)? In this new podcast Associate Editor Robert Hester (University of Mississippi Medical Center) interviews lead author Scott Visovatti (University of Michigan) and content expert Nikki Jernigan (University of New Mexico Health Sciences Center) about the clinically important work by Visovatti and colleagues investigating whether CD39—an extracellular nucleotidase responsible for the dephosphorylation of ATP—could be a key trigger for idiopathic PAH. By first investigating human blood and tissue samples of pulmonary arterial hypertension patients, followed by data from a unique CD39 knockout hypoxic mouse model, Visovatti and co-authors gained valuable insight into the PAH phenotype. What two “rescue approaches” did the authors use to lower right ventricular and pulmonary pressures in the CD39 mouse model? Listen and find out.

Scott H Visovatti, Matthew C Hyman, Sascha N Goonewardena, Anuli C. Anyanwu, Yogendra Kanthi, Patrick Robichaud, Jintao Wang, Danica Petrovic-Djergovic, Rahul Rattan, Charles F. Burant, David J Pinsky Purinergic dysregulation in pulmonary hypertension Am J Physiol Heart Circ Physiol, published May 20, 2016. DOI: 10.1152/ajpheart.00572.2015


Particulate Matter Induced Vascular Insulin Resistance

How are diet-independent insulin resistance and defects in endothelial progenitor cell mobilization altered by particulate matter exposure? Find out by listening to this engaging podcast as Guest Editor Loren Wold (The Ohio State University) interviews lead author Petra Haberzettl (University of Louisville) and content expert Timothy Nurkiewicz (West Virginia University) about the recent study by Haberzettl et al published as part of our Call for Papers on Cardiovascular Responses to Environmental Stress. Haberzettl and co-authors used a mouse model to investigate exposure to fine particulate matter, altered sensitivity of blood vessels, and an inflammatory pathway. What “chicken and egg” problem does NOS uncoupling and oxidative stress pose, related to decreased insulin sensitivity via Akt? Does this work challenge the current literature to look beyond cytokines and interleukin-mediated processes to endothelial progenitor cells in the bone marrow? Listen and learn.

Petra Haberzettl, James P. McCracken, Aruni Bhatnagar, Daniel J. Conklin Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis Am J Physiol Heart Circ Physiol, published June 1, 2016. DOI: 10.1152/ajpheart.00369.2015


Effects of Age and Estrogen on Cerebrovascular Function

Does aging enhance the deleterious effects of exogenous estrogen in the female cerebrovasculature? In this engaging new podcast, Guest Editor Akos Koller (New York Medical College, Valhalla, and University of Physical Education, Budapest) interviews lead author John Stallone (Texas A & M University) and content expert Ines Drenjancevic (University of Osijek, Croatia) about the intriguing new work by Deer et al, which studied the interplay of vascular prostanoids, estrogen, and aging in small cerebral arteries. Why did the authors choose vasopressin to study the reactivity of the cerebral vasculature? How does the uncoupling of nitric oxide synthase to produce oxygen free radicals relate to aging? How does aging convert estrogen from a beneficial to a deleterious hormone? Listen and find out.

Rachel R. Deer, John N. Stallone Effects of estrogen on cerebrovascular function: age-dependent shifts from beneficial to detrimental in small cerebral arteries of the rat Am J Physiol Heart Circ Physiol, published May 15, 2016. DOI: 10.1152/ajpheart.00645.2015.


Diastolic Dysfunction in the Hypertensive mRen2 Rat

Do basic scientists now have a good animal model of heart failure with preserved ejection fraction (HFpEF) that mimics the human pathology? It’s very likely, according to the recent work by Kovacs et al. In this podcast, Editor in Chief Irving H. Zucker interviews lead author Arpad Kovacs (University of Debrecen, Hungary) and content expert Nazha Hamdani (VU University Medical Center, Amsterdam, and Ruhr University, Germany) about the fascinating new work by Kovacs and co-authors which seeks to understand the interplay between the renin-angiotensin-aldosterone system (RAAS) and hypertension in the unique mRen2 rat model of HFpEF. What role do the titin filament network and collagen fibers of the extracellular matrix play in LV diastolic dysfunction? Do the mechanisms underlying diastolic dysfunction hold the key to understanding if the hypertension associated with mRen2 rats is unique to this model or an inevitable consequence of hypertension? Listen now.

Árpád Kovács, Gabor Aron Fulop, Andrea Kovacs, Tamas Csipo, Beata Bodi, Daniel Priksz, Bela Juhasz, Lívia Beke, Zoltán Hendrik, Gábor Méhes, Henk Granzier, Istvan Edes, Miklós Fagyas, Zoltán Papp, Judit Barta, Attila Tóth Renin overexpression leads to increased titin-based stiffness contributing to diastolic dysfunction in hypertensive mRen2 rats Am J Physiol Heart Circ Physiol, published April 8, 2016. DOI: 10.1152/ajpheart.00842.2015


Dilated Cardiomyopathy Delta Sarcoglycan Mutations Cause Cardiomyocyte Membrane Instability

What is the link between mutations in delta sarcoglycans and dilated cardiomyopathy? In our latest podcast, Guest Editor Noah Weisleder (Ohio State University) interviews lead author Daniel Michele (University of Michigan) and content expert Aaron Beedle (University of Georgia) about this very question, digging deeper into the elegant study by Campbell et al which reveals that two different delta sarcoglycan mutations indeed have a dominant negative effect on myocyte membrane mechanical stability. Using a variety of experimental approaches—cellular, biochemical and functional assays—Dr. Michele and co-authors help to uncover the relationship between these genetic mutations and the presentation of the dilated cardiomyopathy phenotype. Learn more about how a personal connection to muscular dystrophy acted as a springboard for this study, part of our Call for Papers on Plasma Membrane Integrity in Cardiovascular Physiology and Pathophysiology. How do delta sarcoglycans guard against sarcolemma instability, and how does membrane repair differ from membrane integrity in dilated cardiomyopathy? Listen and find out.

Matthew D. Campbell, Marc Witcher, Anoop Gopal, Daniel E. Michele Dilated cardiomyopathy mutations in δ-sarcoglycan exert a dominant-negative effect on cardiac myocyte mechanical stability Am J Physiol Heart Circ Physiol, published May 1, 2016. DOI: 10.1152/ajpheart.00521.2015


Aging Impairs Endothelial Ca2+ Signaling

We know that as we age, blood vessels become less effective at getting blood where you need it, when you need it. Intracellular calcium signaling is a key step in regulation of vascular function. Could defects in calcium signaling between the endothelium and smooth muscle cells of microvessels contribute to aging-related vascular dysfunction? Listen as Guest Editor Akos Koller (New York Medical College, Valhalla, and University of Physical Education, Budapest) interviews first author Erika Boerman (University of Missouri - Columbia) and topic expert Jonathan Ledoux (Montreal Heart Institute) about an innovative Rapid Report by Boerman and colleagues. Using an intravital microvascular preparation, Boerman et al combined several innovative techniques from other laboratories, including GCamp 2 mice developed as a calcium biosensor for measuring calcium pulsars, to explore calcium signaling in holes within the internal elastic lamina between the endothelium and smooth muscle. If the number of these holes reduces with aging, is there a corresponding decreased capacity for myoendothelial calcium signaling, which then can contribute to age-related microvascular dysfunction? Listen and learn.

Erika M. Boerman, Jesse E. Everhart, Steven S. Segal Advanced age decreases local calcium signaling in endothelium of mouse mesenteric arteries in vivo Am J Physiol Heart Circ Physiol, published May 1, 2016. DOI: 10.1152/ajpheart.00038.2016.


CpG DNA and Maternal Vascular Function

Preeclampsia affects nearly 10 million pregnancies worldwide every year, and is still a major cause of maternal death globally, particularly in developing countries. So why isn’t more known about the initiation of gestational hypertension? In their recent work published in AJP-Heart and Circulatory Physiology, Goulopoulou et al seek to change that. Listen as Associate Editor Nancy Kanagy interviews Stella Goulopoulou (University of North Texas Health Science Center) and leading expert Lawrence Reynolds (North Dakota State University) about the work by Goulopoulou and co-authors, which used an innovative mitochondrial DNA analog, ODN 2395, to induce activation of toll-like receptor 9 and stimulate maternal pregnancy hypertension in rats. Does placenta cell death released into the maternal circulation trigger the innate immune system to induce a systemic inflammatory response resulting in pregnancy-induced hypertension? Could CpG oligonucleotides from bacterial infections play a role in preeclampsia? Listen and find out.

Styliani Goulopoulou, Camilla F. Wenceslau, Cameron G. McCarthy, Takayuki Matsumoto, R. Clinton Webb Exposure to stimulatory CpG oligonucleotides during gestation induces maternal hypertension and excess vasoconstriction in pregnant rats Am J Physiol Heart Circ Physiol, published April 15, 2016. DOI: 10.1152/ajpheart.00834.2015.


Cardiac Adaptations During a Mountain Ultra-Marathon

Can a mountain ultra-marathon—arguably the most grueling and strenuous form of extreme exercise—be good for your heart? That’s just what we discuss in this latest podcast. Listen as Editor-in-Chief Dr. Irv Zucker interviews lead author Stéphane Nottin (Montpellier I University & Nimes University Hospital Center) and leading expert Michael Joyner (Mayo Clinic) about the work Nottin and colleagues undertook measuring the effects of this type of extreme exercise on the cardiac function of runners before, during, and after the world's most challenging mountain ultra-marathon Tor des Géants in the Italian Alps. While traipsing echocardiographic equipment around the Alps is no small feat, the results of Nottin and co-authors were even more interesting. As opposed to races of shorter duration or less extreme conditions (a typical marathon course, for example), post-race cardiac function improved in the ultra-marathoners. What role does exercise intensity play in these measurements of improved cardiac function? Why does end-diastolic volume increase at the end of the race, and does an increase in plasma volume explain the increase in gastric function in racers? Listen to find out.

Claire Maufrais, Grégoire P. Millet, Iris Schuster, Thomas Rupp, Stéphane Nottin Progressive and biphasic cardiac responses during extreme mountain ultra-marathon Am J Physiol Heart Circ Physiol, published February 26, 2016. DOI: 10.1152/ajpheart.00037.2016.