How can we better understand the developmental nature of cardiovascular disease across the life course and improve the health of people who experience chronic early life stress? In this episode Dr. Nathaniel Jenkins (University of Iowa) interviews lead author Dr. Annemarie Wentzel (North-West University, South African Medical Research Council Unit for Hypertension and Cardiovascular Disease) and expert Dr. Romain Harmancey (The University of Texas Health Science Center at Houston) about the study by Wentzel et al. which found that stress, expressed as a cumulative allostatic load score, impacted the microvasculature, macrovasculature, and central cardiac structure and function on a preclinical level in otherwise healthy emerging adults. The authors also found that the composite allostatic load score was particularly accurate in predicting masked hypertension and pre-diabetes in their study population. The composite allostatic load score incorporates multiple physiological biomarker systems and can offer clinicians an additional tool to use in addressing root causes of chronic stress. Is your hardware for managing stress where it should be developmentally? Listen now and learn more.

A. Wentzel, W. Smith, E. Jansen van Vuren, R. Kruger, Y. Breet, E. Wonkam-Tingang, N. A. Hanchard, and S. T. Chung Allostatic load and cardiometabolic health in a young adult South African population: the African-PREDICT study Am J Physiol Heart Circ Physiol, published February 24, 2025. DOI: 10.1152/ajpheart.00845.2024

The literature shows that the incidence of heart failure with preserved ejection fraction (HFpEF) increases significantly in postmenopausal women, but how can researchers study the underlying mechanisms? In our latest episode, Dr. Jonathan Kirk (Loyola University Chicago) interviews lead author Dr. Mei Methawasin (University of Missouri, Columbia) and expert Dr. Glen Pyle (University of Guelph) about the recent study by Methawasin and co-authors investigating sex differences, menopause and HFpEF. The authors created an animal model that resembles HFpEF in women undergoing natural menopause by using 4-vinylcyclohexene dioxide (VCD) to induce “ovary-intact” menopause, combined with the 2hit regimen (HFpEF inducing regimen) to model postmenopausal HFpEF. Combining echocardiography, pressure-volume and single-cell analyses, the authors found that VCD mice, compared to ovariectomized mice and premenopausal mice, have higher testosterone levels compared to other models. By developing this robust phenotype animal model, the authors open new avenues for investigating therapeutic targets in other hormones beyond estrogen alone. Ready to explore the estrobolome, the importance of animal models of human disease, and the complex family of hormones comprising estrogen? Listen now.

Mei Methawasin, Joshua Strom, Vito A. Marino, Jochen Gohlke, Julia Muldoon, Shelby R. Herrick, Robbert van der Piji, John P. Konhilas, Henk Granzier An ovary-intact postmenopausal HFpEF mouse model; menopause is more than just estrogen deficiency Am J Physiol Heart Circ Physiol, published March 10, 2025. DOI: 10.1152/ajpheart.00575.2024

What is the role of ferroptosis, programmed cell death characterized by intracellular iron accumulation and lipid peroxidation, in the context of ischemic injury related to heart transplantation? In this episode, Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews authors Dr. Kenneth Liao and Dr. Nandan Mondal (both at Baylor College of Medicine), along with expert Dr. Zachary Kiernan (Virginia Commonwealth University) about the latest study by Li et al. The authors found that prolonged cold storage increases the susceptibility of hearts donated after brain death (DBD) to ferroptotic cell death. In contrast, however, the authors found that warm ischemic injury increased the risk for ferroptotic cell death in hearts donated after circulatory death (DCD). Li et al. found that targeting ferroptosis could be beneficial for optimizing cold preservation for DBD hearts, while interventions for DCD hearts should focus on the early phase of warm ischemia. Heart transplantation is the gold standard therapy for patients with medically refractory advanced heart failure. However, demand greatly exceeds supply of donor hearts. Listen as we discuss the current state of the heart transplantation field and the many challenges it faces.

Shiyi Li, Katherine V. Nordick, Abdussalam E. Elsenousi, Rishav Bhattacharya, Randall P. Kirby, Adel M. Hassan, Camila Hochman-Mendez, Todd K. Rosengart, Kenneth K. Liao, and Nandan K. Mondal Warm-ischemia and Cold Storage Induced Modulation of Ferroptosis Observed in Human Hearts Donated After Circulatory Death and Brain Death Am J Physiol Heart Circ Physiol, published March 28, 2025. DOI: 10.1152/ajpheart.00806.2024

Can hormonal fluctuations across a single menstrual cycle alter arterial wave reflections and wasted pressure effort? In this episode, Associate Editor Dr. Jonathan Kirk (Loyola University Chicago) interviews author Dr. Ninette Shenouda (University of Delaware) and expert Dr. Sarah Baker (Mayo Clinic) about the latest study by Shenouda et al. investigating sex differences and ventricular arterial interactions. The authors wanted to understand how strategic phases of the menstrual cycle might affect the relationship between the left ventricle (LV) and the arterial system, as this relationship is crucial for maintaining adequate cardiac output and blood pressure. Given the established beneficial effects of estradiol on the vasculature, the authors hypothesized that their cohort of naturally menstruating premenopausal women would have favorable reductions in total peripheral resistance and favorable changes in the arterial wave reflection profile during the high hormone cycle phases, compared to age matched men. What were the unexpected findings? Listen now to find out.

Ninette Shenouda, Joseph M. Stock, Nicholas V. Chouramanis, Zoe R. Lincoln, Megan M. Wenner, Julio A. Chirinos, and David G. Edwards Favorable alterations in ventricular-arterial interactions across the menstrual cycle in healthy premenopausal women Am J Physiol Heart Circ Physiol, published February 28, 2025. DOI: 10.1152/ajpheart.00363.2024

In this episode, Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) interviews authors Dr. Oliver H. Wearing (University of British Columbia), Dr. Naomi C. Chesler (University of California Irvine), Dr. Mitchel J. Colebank (University of South Carolina), Dr. Timothy A. Hacker (University of Wisconsin-Madison), Dr. John N. Lorenz (University of Cincinnati), and Dr. Christopher R. West (University of British Columbia) about their new Guidelines in Cardiovascular Research article. This must-read Guidelines article provides a thorough overview of ventricular pressure-volume (PV) measurements in the mouse heart. PV measurements are an invasive method for assessment of heart function, and if done correctly, can provide researchers with valuable information about heart hemodynamics and the relationship between changes in ventricular pressure and volume during a cardiac cycle. The authors discuss PV measurements as the gold standard for assessing cardiac in vivo function. How do PV measurements differ from, and provide a complement to, echocardiography measurements? Listen and find out more.

Oliver H. Wearing, Naomi C. Chesler, Mitchel J. Colebank, Timothy A. Hacker, John N. Lorenz, Jeremy A. Simpson, and Christopher R. West Guidelines for assessing ventricular pressure-volume relationships in rodents Am J Physiol Heart Circ Physiol, published January 2, 2025. DOI: 10.1152/ajpheart.00434.2024

In our latest episode, Dr. Jeff Saucerman (University of Virginia) interviews authors Dr. Naomi Chesler (University of California, Irvine) and Dr. Mitchel Colebank (University of South Carolina) about their new Guidelines in Cardiovascular Research article on incorporating mechanistic modeling into the analysis of experimental and clinical data to identify possible mechanisms of (ab)normal cardiovascular physiology. The authors’ goal is to provide a consensus document that identifies best practices for in silico computational modeling in cardiovascular research. These guidelines provide the necessary methods for mechanistic model development, model analysis, and formal model calibration using fundamentals from statistics. Colebank et al. outline rigorous practices for computational, mechanistic modeling in cardiovascular research and discuss its synergistic value to experimental and clinical data. Would you like to understand how to apply a cone of uncertainty to your experimental data? Listen now to find out more.

Mitchel J. Colebank, Pim A. Oomen, Colleen M. Witzenburg, Anna Grosberg, Daniel A. Beard, Dirk Husmeier, Mette S. Olufsen, and Naomi C. Chesler Guidelines for mechanistic modeling and analysis in cardiovascular research Am J Physiol Heart Circ Physiol, published August 6, 2024. DOI: 10.1152/ajpheart.00253.2024

In this episode of Behind the Bench, we are talking with Hannah Cizauskas about her first, first-author article published in AJP-Heart and Circ. Born and raised in Detroit, Hannah moved to Chicago for what she thought would be just one rotation outside of the cancer genetics field. This led Hannah to work on a project related to atrial fibrillation and contractile dysfunction in Dave Barefield’s lab at Loyola University Chicago’s Cellular and Molecular Physiology Department. Now in the fourth year of her PhD, Hannah is a dog mom to Jake, she loves reading STEMinist novels, and she is researching sarcomere dysfunction in the context of AFib. Listen to this engaging interview with co-hosts Dr. Tommy Martin and Dr. Charlotte Usselman to find out more.

Hannah E. Cizauskas, Hope V. Burnham, Azaria Panni, Alexandra Peña, Alejandro Alvarez-Arce, M. Therese Davis, Kelly N. Araujo, Christine E. Delligatti, Eby Edassery, Jonathan A. Kirk, Rishi Arora, and David Y. Barefield Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation Am J Physiol Heart Circ Physiol, published August 5, 2024. DOI: 10.1152/ajpheart.00148.2024

In our latest episode, Executive Editor Kara Hansell Keehan interviews lead author Dr. Michaela Patterson and first author Kaelin Akins (both at the Medical College of Wisconsin) along with expert Dr. Ana Vujic (University of Cambridge) about the new study by Akins et al. Given that the heart has limited regenerative potential, repairing damage to cardiomyocytes after a heart attack is particularly challenging. Cardioregeneration researchers worldwide are searching for potential targets that can stimulate cardiomyocyte proliferation and cardiac regeneration. However, because cardiomyocytes can undergo incomplete cell division, multinucleation, and polyploidization, it is difficult to study true cardiomyocyte proliferation. Akins et al. examined the effect of Runx1 on cardiomyocyte cell cycle during postnatal development and cardiac regeneration using cardiomyocyte-specific gain- and loss-of-function mouse models. Listen now to learn more about how the authors determined that Runx1 is sufficient but not required for cardiomyocyte cell cycle activation.

Kaelin A. Akins, Michael A. Flinn, Samantha K. Swift, Smrithi V. Chanjeevaram, Alexandra L. Purdy, Tyler Buddell, Mary E. Kolell, Kaitlyn G. Andresen, Samantha Paddock, Sydney L. Buday, Matthew B. Veldman, Caitlin C. O’Meara, Michaela Patterson Runx1 is sufficient but not required for cardiomyocyte cell-cycle activation Am J Physiol Heart Circ Physiol, published July 21, 2024. DOI: 10.1152/ajpheart.00782.2023

What is the impact of central insulin on muscle sympathetic nerve activity (MSNA) and vascular conductance in the absence of peripheral insulin delivery? Listen as Associate Editor Dr. Jason Carter (Baylor University) interviews authors Neil McMillan and Dr. Jackie Limberg (both at University of Missouri), along with expert Dr. Manda Keller-Ross (University of Minnesota), about the new Short Report by McMillan et al. To gain a better understanding of the central sympathoexcitatory effects of insulin in humans, the authors recruited two groups of young, healthy individuals. One group served as a time control and the other group received intranasal insulin administration. McMillan et al. measured MSNA from the fibular nerve, combined with continuous monitoring of blood pressure and leg blood flow, before and after insulin administration. Limberg, McMillan and co-authors found that only the individuals who received insulin exhibited an increase in efferent sympathetic nervous system activity, which was coupled with peripheral vasoconstriction and increases in arterial blood pressure. How does this research influence our mechanistic understanding of the sympathetic and hemodynamic response to insulin? Listen now to find out.

Neil J. McMillan, Dain W. Jacob, Brian Shariffi, Jennifer L. Harper, Glen E. Foster, Camila Manrique-Acevedo, Jaume Padilla, and Jacqueline K. Limberg Effect of acute intranasal insulin administration on muscle sympathetic nerve activity in healthy young adults Am J Physiol Heart Circ Physiol, published July 3, 2024. DOI: 10.1152/ajpheart.00253.2024

Sometimes experimental results are serendipitous. Listen as Associate Editor Dr. Crystal Ripplinger (University of California, Davis) talks with authors Dr. Nikki Posnack and Devon Guerrelli (both at Children’s National Hospital and The George Washington University School of Engineering and Applied Science), along with expert Dr. Silvia Marchiano (University of Washington), about the new research by Guerrelli et al. published in our Call for Papers on Excitation-Contraction Coupling, Electrophysiology, and Arrhythmias. The Posnack Lab typically investigates environmental chemicals and their impact on cardiac function using microelectrode arrays to record electrical signals from human iPS cells. When performing cardiotoxicity experiments, the authors realized that their baseline measurements varied significantly between their different studies, making it difficult to combine datasets. In doing the legwork to identify potential sources of variability and improve their own internal lab protocols, the authors focused on the reproducibility of their experimental measurements using human iPSCs. Listen as we discuss important recommendations for investigators using these cells to improve their experimental reproducibility.

Devon Guerrelli, Jenna Pressman, Shatha Salameh, and Nikki Posnack hiPSC-CM Electrophysiology: Impact of Temporal Changes and Study Parameters on Experimental Reproducibility Am J Physiol Heart Circ Physiol, published June 9, 2024. DOI: 10.1152/ajpheart.00631.2023