AJP-Heart and Circulatory Physiology Podcast

DCM Mutations Alter Intracellular Ca2+ and Signaling

What can three mutations in thin filament regulatory proteins associated with dilated cardiomyopathy tell us about the highly variable phenotypes of DCM? Listen as Associate Editor Crystal Ripplinger (University of California Davis) interviews lead author Paul Robinson (University of Oxford) and expert Michael Greenberg (Washington University in St. Louis) about the latest work by Robinson and co-authors. By studying functional changes in cardiomyocyte contraction, calcium handling and signaling, Robinson and co-authors hoped to identify common pathway activations in troponin T, troponin I and tropomyosin mutations. Why did the authors opt to study DCM mutations in guinea pig cardiomyocytes rather than in a mouse model? Given the substantial number of mutations in both pediatric and adult-onset DCM, what are the implications here for precision medicine in the treatment of this disease? Listen to learn more.

 

Paul Robinson, Alexander J. Sparrow, Suketu Patel, Marta Malinowska, Svetlana N. Reilly, Yin-Hua Zhang, Barbara Casadei, Hugh Watkins, Charles Redwood Dilated cardiomyopathy mutations in thin-filament regulatory proteins reduce contractility, suppress systolic Ca2+, and activate NFAT and Akt signaling Am J Physiol Heart Circ Physiol, published July 21, 2020. DOI: doi.org/10.1152/ajpheart.00272.2020

Endothelial ERBB4 and Cardiac Remodeling

Does neuregulin-1 autocrine signaling by endothelial cells regulate left ventricular remodeling? Listen as Deputy Editor Merry Lindsey (University of Nebraska Medical Center) interviews lead authors Gilles De Keulenaer and Vincent Segers (both at University of Antwerp), along with expert Ganesh Halade (University of South Florida), about the novel work by Dugaucquier et al. The authors investigated responses to pressure overload using transverse aortic constriction, angiontensin II infusion, and myocardial infarction, in an endothelial cell-specific ERBB4 knockout mouse model. Surprising results serve to highlight the spatial and temporal heterogeneity of left ventricular autocrine and paracrine responses to cardiac injury. What’s more, these results lead the authors to believe that paracrine and autocrine signaling are integrally connected and equally influential on cardiac remodeling. “By performing this study, we now look at autocrine signaling in the myocardium in a completely different fashion,” explained De Keulenaer. Why? Listen now.

 

Lindsey Dugaucquier, Eline Feyen, Ligia Mateiu, Tine Anne Marie Bruyns, Gilles W. De Keulenaer, Vincent F. M. Segers The role of endothelial autocrine NRG1/ERBB4 signaling in cardiac remodeling Am J Physiol Heart Circ Physiol, published August 4, 2020. DOI: doi.org/10.1152/ajpheart.00176.2020

Behind the Bench Episode 6 with Aurore Lyon

Everyone has a story, and no one is ordinary. That’s our theme for this episode of Behind the Bench from AJP-Heart and Circ. Hosts Lisandra de Castro Bras (East Carolina University) and Jonathan Kirk (Loyola University Chicago) talk with Aurore Lyon (Maastricht University), the first author of “Differentiating the effects of beta-adrenergic stimulation and stretch on calcium and force dynamics using a novel electromechanical cardiomyocyte model,” published in August 2020. Aurore pursued a master’s degree, followed by a PhD, at Oxford University. She is now completing a post-doctoral fellowship in the Department of Biomedical Engineering within the Cardiovascular Research Institute Maastricht at Maastricht University. Aurore’s story is about finding a passion in an unexpected field while pursuing research in a completely different area. From engineering to cardiovascular research, Aurore brings a refreshing perspective to navigating career and life across countries and cultures. Ready to change directions in your own career? Listen for inspiration.

 

Aurore Lyon, Lauren J. Dupuis, Theo Arts, Harry J. G. M. Crijns, Frits W. Prinzen, Tammo Delhaas, Jordi Heijman, Joost Lumens Differentiating the effects of β-adrenergic stimulation and stretch on calcium and force dynamics using a novel electromechanical cardiomyocyte model Am J Physiol Heart Circ Physiol, published August 19, 2020. DOI: doi.org/10.1152/ajpheart.00275.2020

Vascular Response to Prolonged Sitting in Hypercapnia

What are the potential detrimental interactions between prolonged sitting and mild hypercapnia on autonomic system activity, vascular function, and microvascular oxygenation? In this episode, Editor-in-Chief Irv Zucker (University of Nebraska Medical Center) interviews lead author Song-Young Park (University of Nebraska at Omaha) and expert Camilla Wenceslau (University of Toledo) about the latest study by Headid et al., which found that prolonged sitting attenuated systemic and peripheral vascular endothelial function, as well as microvascular function in healthy adults. Park and co-authors also found that prolonged sitting coupled with mild hypercapnic conditions that mimic everyday environments in workplaces, office buildings, and school classrooms resulted in exacerbated peripheral vascular and microvascular dysfunction. Listen as we discuss how prolonged sitting may aggravate disease conditions such as sleep apnea, COPD, and obesity. What are the potential implications of this research for students spending long hours sitting indoors with restricted movement due to COVID-19 pandemic restrictions? Listen to find out.

 

Ronald J. Headid 3rd, Elizabeth J. Pekas, TeSean K. Wooden, Won-Mok Son, Gwenael Layec, John Shin, Song-Young Park Impacts of prolonged sitting with mild hypercapnia on vascular and autonomic function in healthy recreationally active adults Am J Physiol Heart Circ Physiol, published August 4, 2020. DOI: doi.org/10.1152/ajpheart.00354.2020

[U-13C]-glucose and In Vivo Heart Metabolism

What is the “metabolic fate” of glucose in mice with pressure-overload or volume-overload induced cardiac hypertrophy? Listen as Associate Editor Fabio Recchia (Temple University and Scuola Superiore Sant'Anna) interviews lead author, and fellow Associate Editor, Ajay Shah (King’s College London) along with experts Christoph Maack and Edoardo Bertero (both at University Clinic Würzburg) about the new study by Schnelle et al. “Metabolism is integrally linked to structural and functional changes that occur in the remodeling heart.” By implementing a method of heavy carbon labeling in vivo, and utilizing nuclear magnetic resonance spectroscopy, Schnelle et al. found notable differences in the pressure-overload mouse model of transverse aortic constriction (TAC) but not in the volume-overload TAC model. What is the significance of an increase in flux in the tricarboxylic acid cycle (TCA) during pressure-overload? How did the authors interpret the evidence of increased glutamine and aspartate, neither of which are TCA metabolites? Listen to find out.

 

Moritz Schnelle, Mei Chong, Anna Zoccarato, Manar Elkenani, Greta Jane Sawyer, Gerd Hasenfuss, Christian Ludwig, Ajay M. Shah In vivo [U-13C]glucose labeling to assess heart metabolism in murine models of pressure and volume overload Am J Physiol Heart Circ Physiol, published August 4, 2020. DOI: doi.org/10.1152/ajpheart.00219.2020

Assessment of Diastolic Function

Listen as Deputy Editor Merry Lindsey (University of Nebraska Medical Center) interviews authors Leslie Ogilvie and Jeremy Simpson (University of Guelph) and expert Michael Czubryt (University of Manitoba) about the recent Review by Ogilvie et al. on the importance of evaluating best practices in the hemodynamic assessment of diastolic function for animal models. With significant clinical focus on the role diastolic dysfunction plays in heart failure with preserved ejection fraction (HFpEF), cardiac fibrosis, and diabetes, there is no better time to examine diastolic functional assessments in experimental models. “Diastolic function has emerged as being equally important to systolic function in the overall ability of the heart to function as a pump,” explains Simpson. We discuss rodent models of human diastolic dysfunction in the setting of HFpEF, and understanding diastolic function in terms of its two phases—relaxation and filling. What recommendations do Ogilvie and Simpson make for handling the inherent limitations of software-based algorithms? Listen and learn more.

 

Leslie M. Ogilvie, Brittany A. Edgett, Jason S. Huber, Mathew J. Platt, Hermann J. Eberl, Sohrab Lutchmedial, Keith R. Brunt, Jeremy A. Simpson Hemodynamic assessment of diastolic function for experimental models Am J Physiol Heart Circ Physiol, published April 21, 2020. DOI: doi.org/10.1152/ ajpheart.00705.2019

Race, Blood Pressure, and Microvascular Function

Does pre-hypertension, or Stage 1 hypertension, have adverse effects on the microvasculature and the ability of blood vessels to vasodilate? In this episode, Associate Editor Nisha Charkoudian (U.S. Army Research Institute of Environmental Medicine) interviews lead author Brett Wong (Georgia State University) and expert Anna Stanhewicz (University of Iowa) about the new study by Wong and co-authors, in which a local heating protocol on the skin was used to investigate whether race and/or blood pressure affect sensory nerve function. The authors found that both sensory nerve function and microvascular nitric oxide function were reduced in pre-hypertensive non-Hispanic black study participants compared to non-Hispanic white study participants. Even in the absence of overt cardiovascular disease, the work by Wong and co-authors detected changes in the mechanisms controlling blood flow. How do the racial differences observed in this study challenge the “one size fits all” concept of preventative cardiovascular healthcare? Listen now.

 

Brett J. Wong, Casey G. Turner, James T. Miller, Demetria C. Walker, Yesser Sebeh, Matthew J. Hayat, Jeffrey S. Otis, Arshed A. Quyyumi Sensory nerve-mediated and nitric oxide-dependent cutaneous vasodilation in normotensive and prehypertensive non-Hispanic blacks and whites Am J Physiol Heart Circ Physiol, published July 14, 2020. DOI: doi.org/10.1152/ajpheart.00177.2020

Behind the Bench Episode 5

In this episode we take a look behind Behind the Bench, and turn the tables to interview the interviewers. Editor-in-Chief Dr. Irv Zucker (University of Nebraska Medical Center) talks with Dr. Lisandra de Castro Bras (East Carolina University) and Dr. Jonathan Kirk (Loyola University Chicago), our Behind the Bench podcast hosts. How did they both get started in science? What is their best advice to trainees launching their own careers in physiology? And how did this whole “Behind the Bench” podcast come about in the first place? So many questions. Let’s dive in.

 

Smoking Effects on Ventricular Repolarization

We know that smoking increases the risk of sudden cardiac death, which is linked to changes in ventricular repolarization. Is there a difference in sudden cardiac death risk between smoking tobacco cigarettes vs. e-cigarettes? Associate Editor Nisha Charkoudian (U.S. Army Research Institute for Environmental Medicine) interviews lead author Holly Middlekauff (University of California Los Angeles) and content expert Marmar Vaseghi (University of California Los Angeles) about the new study by Ip et al. In this study, the authors compared electrocardiogram indices of ventricular repolarization in tobacco smokers before and after smoking a tobacco cigarette, as well as e-cigarette vapers before and after smoking an e-cigarette—once with and once without nicotine. Acute nicotine intake was the same among both types of smokers. However, three ECG indices of repolarization were significantly prolonged in tobacco smokers after smoking, whereas one of three indices was prolonged in e-cigarette smokers after vaping. What do these findings indicate about the sudden cardiac death risk of e-cigarettes compared to tobacco cigarettes? Does the e-cigarette rate of nicotine delivery have an impact on physiological effects? Listen now to learn how to present an evidence-based argument the next time a friend (or your child) tells you e-cigarettes are “safer” than smoking.

 

Michelle Ip, Evangelos Diamantakos, Kacey Haptonstall, Yasmine Choroomi, Roya S. Moheimani, Kevin Huan Nguyen, Elizabeth Tran, Jeffrey Gornbein, Holly R. Middlekauff Tobacco and electronic cigarettes adversely impact ECG indexes of ventricular repolarization: implication for sudden death risk  Am J Physiol Heart Circ Physiol, published April 21, 2020. DOI: doi.org/10.1152/ajpheart.00738.2019

PTSD and Sympathetic Action Potential Discharge Pattern

Women develop post-traumatic stress disorder (PTSD) at twice the rate of men, and women with PTSD are at higher risk for developing hypertension. Yet little research has been done to date investigating the mechanisms mediating the link between PTSD and cardiovascular disease in women. The study by Yoo et al. seeks to change that. Associate Editor Donal O’Leary (Wayne State University School of Medicine) interviews lead author Qi Fu (The Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas) and expert Adam Case (University of Nebraska Medical Center) about the groundbreaking and clinically-relevant study by Fu and co-authors. The authors showed for the first time that women with PTSD had a greater pressor response during the cold pressor test compared with healthy women. What insights did Fu and collaborators uncover when they compared results from traditional methods to quantify integrated nerve signals, and a novel wavelet-based technique used to identify differences in MSNA responses to cold pressor test between women with PTSD and healthy women? Do Fu and Case anticipate that the current COVID-19 pandemic, while undeniably tragic, may eventually open new avenues of discovery for how women with PTSD differ from healthy counterparts and men? Listen and learn.

 

Jeung-Ki Yoo, Mark B. Badrov, Mu Huang, Ryan A. Bain, Raymond P. Dorn, Elizabeth H. Anderson, Jessica L. Wiblin, Alina Suris, J. Kevin Shoemaker, Qi Fu Abnormal sympathetic neural recruitment patterns and hemodynamic responses to cold pressor test in women with posttraumatic stress disorder Am J Physiol Heart Circ Physiol, published April 27, 2020. DOI: 10.1152/ajpheart.00684.2019