AJP-Heart and Circulatory Physiology Podcast

Heart Failure Alters Synaptic Input in Cardiac Vagal Neurons

Is a reduction in parasympathetic activity the “canary in the coal mine” at the onset of many cardiovascular diseases, such as hypertension and heart failure? Listen as Associate Editor Kaushik Patel (University of Nebraska Medical Center) interviews lead author David Mendelowitz (George Washington University) and content expert Helio Salgado (University of São Paulo) about why Cauley et al set out to understand what changes cardiac vagal activity at the level of the brainstem using an aortic constriction model of heart failure. While much is known about alterations in sympathetic nerve activity, the knowledge of parasympathetic activity is still in its infancy. Could leveraging the diverse populations of neurons within the paraventricular nucleus of the hypothalamus provide a mechanism to alter the sympathetic-parasympathetic balance? Would stimulating parasympathetic activity, either at the level of the ganglia or brainstem, provide cardioprotective benefits in cardiovascular diseases, such as hypertension and heart failure? Listen to find out.

Edmund Cauley, Xin Wang, Jhansi Dyavanapalli, Ke Sun, Kara Garrott, Sarah Kuzmiak-Glancy, Matthew W Kay, David Mendelowitz Neurotransmission to Parasympathetic Cardiac Vagal Neurons in the Brainstem is Altered With Left Ventricular Hypertrophy Induced Heart Failure Am J Physiol Heart Circ Physiol, published September 14, 2015, DOI: 10.1152/ajpheart.00445.2015.

CLIC4 Regulates Maturation of Cerebral Collaterals

What are collateral arterioles, and how can the number of such collaterals in the brain affect recovery from stroke? Listen as Guest Editor Akos Koller (New York Medical College) interviews first author Jennifer Lucitti (University of North Carolina at Chapel Hill) and content expert Mordecai Blaustein (University of Maryland Medical School) about this fascinating new study, which investigated the formation of collaterals both pre- and postnatal, as well as the role of chloride intracellular channel 4 (CLIC4) protein in collateral formation. Lucitti and colleagues found that there is a specific time when collaterals formed during embryogenesis, which can be very important later in life if larger arteries are blocked. At the molecular level, what exciting relationship did the authors find between vascular endothelial growth factor-A (VEGF-A) and CLIC 4 during collaterogenesis? Is prevention of collateral pruning and enhancement of collateral stabilization later in life a promising therapeutic target for stroke? Listen now.

Jennifer L. Lucitti, Natalie J. Tarte, James E. Faber Chloride intracellular channel 4 is required for maturation of the cerebral collateral circulation Am J Physiol Heart Circ Physiol, published October 1, 2015, DOI: 10.1152/ajpheart.00451.2015.

Cardioprotective Effects of Intrinsic STAT3 in Subacute MI

While STAT3 has been shown to protect the heart post myocardial infarction during cardiac remodeling, is persistent activation of the STAT3 gene protecting or hurting the heart? In the English version of this dual language podcast, Associate Editor Junichi Sadoshima (Rutgers New Jersey Medical School) interviews lead author Yasushi Fujio (Osaka University) and content expert Yasuko Bando (Nagoya University) about the innovative work by Enomoto et al, in which Fujio and his collaborators created cardiac-specific conditional STAT3 knockout mice designed to knockout STAT3 only after myocardial infarction. In STAT3 null mice, ROS production increased, which then lead to a cascade of negative effects, first inducing cardiac hypertrophy, then suppressing angiogenesis. Is suppression of superoxide production the primary cardioprotective pathway of STAT3? Listen to learn more.

Daichi Enomoto, Masanori Obana, Akimitsu Miyawaki, Makiko Maeda, Hiroyuki Nakayama, Yasushi Fujio Cardiac-specific ablation of the STAT3 gene in the subacute phase of myocardial infarction exacerbated cardiac remodeling Am J Physiol Heart Circ Physiol, published August 1, 2015, DOI: 10.1152/ajpheart.00730.2014.

JAPANESE LANGUAGE PODCAST: Cardioprotective Effects of Intrinsic STAT3 in Subacute MI

In this Japanese language version of the podcast, Associate Editor Junichi Sadoshima (Rutgers New Jersey Medical School) interviews lead author Yasushi Fujio (Osaka University) and content expert Yasuko Bando (Nagoya University) in Japanese about the innovative work by Enomoto et al, in which Fujio and his collaborators created cardiac-specific conditional STAT3 knockout mice designed to knockout STAT3 only after myocardial infarction. In STAT3 null mice, ROS production increased, which then lead to a cascade of negative effects, first inducing cardiac hypertrophy, then suppressing angiogenesis. Is suppression of superoxide production the primary cardioprotective pathway of STAT3? Listen to learn more.

Daichi Enomoto, Masanori Obana, Akimitsu Miyawaki, Makiko Maeda, Hiroyuki Nakayama, Yasushi Fujio Cardiac-specific ablation of the STAT3 gene in the subacute phase of myocardial infarction exacerbated cardiac remodeling Am J Physiol Heart Circ Physiol, published August 1, 2015, DOI: 10.1152/ajpheart.00730.2014.

VNS Mitigates Neuronal and Myocyte Remodeling Following MI

After more than 40 years of studying the complexities of neural control of myocardial function, what are we learning now about how the intrinsic cardiac nervous system is dominated by intracardiac ganglia that both send and receive information from the heart? Editor in Chief Dr. Irving H. Zucker explores this and more in a new author interview with lead author Jeffrey Ardell (UCLA School of Medicine) and content expert David Mendelowitz (George Washington University) about the fascinating new work by Beaumont et al about vagal nerve stimulation and cardiac neuromodulation. What is the role of these intracardiac ganglia in the remodeling process of myocytes and the cardiac nervous system following myocardial ischemia? Did Ardell and colleagues find that vagal nerve stimulation could restore the central vagal drive and sustain contractile function in the case of chronic ischemia? Listen to find out.

Eric Beaumont, Elizabeth Marie Southerland, Jean C. Hardwick, Gary L Wright, Shannon Ryan, Ying Li, Bruce H. KenKnight, John Andrew Armour, Jeffrey Laurence Ardell Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling post myocardial infarction Am J Physiol Heart Circ Physiol, published online August 14, 2015, DOI: 10.1152/ajpheart.00393.2015.

Diabetic Pregnancy Impairs Function of Endothelial K+ Channels

While it is known that diabetic pregnant women are at significantly higher risk for developing preeclampsia, what are the mechanisms underlying this increasingly common pregnancy complication among diabetic women? In this podcast Editor in Chief Dr. Irving H. Zucker interviews lead author Natalia Gokina (University of Vermont College of Medicine) and content expert David X. Zhang (Medical College of Wisconsin) about the multi-faceted work by Gokina and colleagues, which takes both physiological and pharmacological approaches to investigating the role of two types of calcium-activated potassium channels in abnormalities in uterine blood flow in diabetes. How is downstream signaling impacted, such as ROS production and nitric oxide? Why was there no change in transcription nor protein expression of IK_Ca, despite reduction in IK currents? Listen and learn more.

Natalia I. Gokina, Adrian D. Bonev, Julie Phillips, Alexander P. Gokin, Kelsey Veilleux, Karen Oppenheimer, Gabriela Goloman Impairment of IK_Ca channels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy Am J Physiol Heart Circ Physiol, published August 15, 2015, DOI: 10.1152/ajpheart.00901.2014.

Ventricular Arrhythmias and Fibrosis in Mice

Is interstitial fibrosis a contributor, among other factors, in the prognosis for patients at high risk for arrhythmias? Yes, according to a new study by Nguyen et al. In this podcast Deputy Editor Merry Lindsey (University of Mississippi Medical Center) interviews lead author Xiao-Jun Du (Baker IDI Heart and Diabetes Institute) about his lab’s latest work exploring the interplay between ventricular arrhythmias, cardiac fibrosis, and the resulting functional consequences. Using a transgenic mouse model of spontaneous ventricular tachyarrhythmias and employing detailed telemetry data analysis, Du and colleagues connected the increase in collagen content and collagen cross-linking with an increase over time in arrhythmia episodes. Is connexin 43 upregulated via cardiomyocytes or fibroblasts? Do interventions using antioxidative stress, such as treating with relaxin, reduce fibrosis and therefore reduce the incidents of arrhythmias? Listen to find out.

My-Nhan Nguyen, Helen Kiriazis, Diego Ruggiero, Xiao-Ming Gao, Yidan Su, Anne Jian, Li-Ping Han, Julie R McMullen, Xiao-Jun Du Spontaneous ventricular tachyarrhythmias in β2-adrenoceptor transgenic mice in relation to cardiac interstitial fibrosis Am J Physiol Heart Circ Physiol, published online June 26, 2015, DOI: 10.1152/ajpheart.00405.2015.

Voluntary Exercise in Heart Failure Rats

Exercise guidelines exist for the management and treatment of patients with most cardiovascular diseases, but where does pulmonary arterial hypertension fit into the exercise training therapy picture? In this podcast Guest Editor Shawn Bender interviews lead author Ed White (University of Leeds) and content expert Daphne Merkus (Erasmus MC, Netherlands) about the work by Natali and co-authors, which used an innovative rat model of voluntary wheel running to determine whether exercise training could be beneficial in the treatment of pulmonary artery hypertension (PAH) and right ventricular failure. The authors found that, while wheel running did not prevent the development of PAH, it did significantly delay the median time to heart failure. Will the work by White and collaborators lead to new “off the shelf” exercise training treatments, which could be utilized by clinicians in the treatment of human patients with PAH? Listen and find out.

Antonio José Natali, Ewan Douglas Fowler, Sarah Calaghan, Ed White Voluntary exercise delays heart failure onset in rats with pulmonary artery hypertension Am J Physiol Heart Circ Physiol, published August 1, 2015, DOI: 10.1152/ajpheart.00262.2015.

Post-Heat Stress Cardiovascular Dysregulation

If core temperature is not the primary determinant of heat stroke severity, what is? In this latest podcast, Guest Editor Michael Falvo (VA NJ Health Care System; Rutgers New Jersey Medical School) interviews authors Gerald Audet and Nisha Charkoudian (both of US Army Research Institute of Environmental Medicine), along with content expert Robert Matthew Brothers (University of Texas at Austin), about the innovative work by Quinn et al centered on a unique rat model seeking to identify the failures of the cardiovascular system after heat stroke, rather than during heat stroke. What role do reactive oxygen species and the systemic inflammatory cascade play in governing heart rate and arterial pressure responses observed by the authors? How does this experimental model translate to patient populations, such as the elderly or workers doing physical labor, whose cardiovascular reserves are already taxed when heat stress or heat stroke occurs? Listen and learn.

Carrie M. Quinn, Gerald N. Audet, Nisha Charkoudian, Lisa R. Leon Cardiovascular and thermoregulatory dysregulation over 24 h following acute heat stress in rats Am J Physiol Heart Circ Physiol, published August 15, 2015, DOI: 10.1152/ajpheart.00918.2014.

Optical Projection Tomography for Infarct Assessment

Is optical projection tomography (OPT) useful for producing more than just beautiful images? Yes, according to Zhao et al, who employed the innovative OPT methodology to quantify infarct size experimentally. In this podcast, Associate Editor Ajay Shah (King's College London) interviews lead author Gillian Gray (University of Edinburgh) and content expert Michael Marber (The Rayne Institute, St. Thomas' Hospital, King’s College London) about how Gray and colleagues used OPT to image the heart and capture 3-dimensional measurement of infarct volume. How does OPT stack up against standard histology and MRI? What exactly is giving rise to the autofluorescence signal when using OPT? Is there a future for OPT as a method of measuring infarct volume to transcend biological variations and the limitations of measuring individual sections of infarcted tissue? Listen to find out.

Xiaofeng Zhao, Junxi Wu, Calum D. Gray, Kieran McGregor, Adriano G Rossi, Harris Morrison, Maurits A Jansen, Gillian A Gray Optical projection tomography permits efficient assessment of infarct volume in the murine heart post-myocardial infarction Am J Physiol Heart Circ Physiol, published online June 12, 2015, DOI: 10.1152/ajpheart.00233.2015.