Ep. 1: Cardiovascular Pathophysiology In the Setting of Spinal Cord Injury

May 4, 2022

In the kickoff episode of the 2022 Cardiovascular Connections Series, Dr. Christopher West, Associate Professor in the Department of Cellular & Physiological Sciences at The University of British Columbia and Director of the Translational Integrative Physiology Laboratory, examines the autonomic and cardiovascular consequences of spinal cord injury that extend well beyond the paralysis that has historically dominated SCI research. Using rat and porcine contusion models at the T2/T3 spinal segment alongside patient population data, West demonstrates that SCI produces reduced sympathetic nerve activity, lower blood pressure, diminished cardiac volume and contractility, and cardiomyocyte atrophy, with roughly a 30% sustained reduction in pressure-generating capacity. He discusses acute interventions aimed at improving cord perfusion to limit secondary injury and chronic approaches including intermittent hypoxia and epidural stimulation to restore autonomic control. Sponsored by Transonic Systems.

Key Highlights

• Meta-analysis of echocardiographic studies shows individuals with SCI have lower left ventricular volumes, dimensions, and mass indices than able-bodied controls while maintaining equivalent ejection fractions, with tetraplegic individuals showing no significant change in heart rate or stroke volume at maximum exercise intensity, an effect absent in paraplegic individuals.
• Novel rat and porcine models using midline contusion injury at the T2/T3 segment replicate the incomplete injuries seen clinically and reveal reduced sympathetic nerve activity, blood pressure, cardiac volume and contractility, and increased cardiomyocyte atrophy, with roughly a 30% long-term reduction in pressure-generating capacity.
• Acute interventions that increase blood flow and spinal cord perfusion can limit secondary injury, while chronic approaches including intermittent hypoxia to promote carotid artery plasticity and epidural stimulation to improve spinal circuitry and cardiac pressure offer routes to restore autonomic and motor function.

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Ep. 2: Vascular Contributions to Dementia

May 18, 2022

Dr. Ashley Walker, Assistant Professor of Human Physiology at the University of Oregon, examines how age-related arterial stiffening and endothelial dysfunction contribute to Alzheimer's disease pathology, noting that vascular biomarkers are among the first to change in dementia and may act as initiating factors. Her research demonstrates that stiffening of large arteries including the aorta and carotid artery transmits high-intensity pulse pressures into smaller cerebral arteries that lack sufficient elastic lamina to absorb them, producing oxidative stress, impaired neurovascular coupling, and blood brain barrier leakage. Walker also highlights the underexplored role of sex differences, given that two-thirds of Alzheimer's patients are women and that women exhibit higher rates of arterial stiffness and cerebral flow pulsatility than men.

Key Highlights

• Endothelial cells lining cerebral arteries regulate blood brain barrier exchange and direct blood flow to active neurons through neurovascular coupling, a process requiring easy constriction and dilation that becomes progressively impaired with age, leading to oxidative stress, reduced cerebral perfusion, and memory deficits.
• Large artery stiffening acts as a double-edged sword by protecting against strenuous pulse pressures in youth while pushing high-intensity pulses deeper into smaller cerebral arteries that have fewer elastic lamina and are poorly equipped to handle them, with mice bearing isolated large artery stiffening showing reductions in vasodilation comparable to aged mice alongside greater oxidative stress.
• Someone in the United States develops Alzheimer's disease every 65 seconds, and with two-thirds of patients being women and women showing higher arterial stiffness and cerebral flow pulsatility than men, sex-specific hormonal contributions to vascular dysfunction represent a critical research gap.

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Ep. 3: COVID-19, Endotheliitis, & Long-Term Cardiovascular Effects

June 7, 2022

Dr. Augusto Montezano, Research Associate in Cardiovascular Medicine at the McGill University Health Centre and former Walton Fellow at the University of Glasgow Institute of Cardiovascular and Medical Sciences, investigates how SARS-CoV-2 drives endothelial inflammation and long-term cardiovascular complications through ACE2 biology. By exposing human microvascular endothelial cells to recombinant spike protein S1 subunit, his group demonstrated that the S1 subunit triggers a potent inflammatory response in an ACE2-dependent manner without altering ACE2 enzymatic activity. Montezano's findings indicate that vascular inflammation in COVID-19 involves ACE2-mediated pro-inflammatory signaling that may occur independently of viral replication.

Key Highlights

• ACE2 interaction with the SARS-CoV-2 spike protein S1 subunit is central to viral entry, and the cardiovascular complications associated with COVID-19 are thought to arise from endothelial cell inflammation rather than direct cardiac injury alone.
• Recombinant S1 protein applied to human microvascular endothelial cells induces a potent inflammatory response through an ACE2-dependent mechanism while leaving ACE2 enzymatic activity unaffected, isolating receptor-mediated signaling from catalytic function.
• Because the inflammatory response can be triggered by spike protein alone, vascular inflammation in COVID-19 may proceed independently of viral replication, offering a mechanistic explanation for persistent endothelial dysfunction and long-term cardiovascular effects after infection.

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Ep. 4: Moving for a Better Beat: How Exercise Benefits the Heart

June 22, 2022

Professor Louise Naylor of the School of Human Sciences at The University of Western Australia examines how different modes of exercise produce distinct cardiac adaptations and how exercise can be prescribed to restore function after cardiovascular events. Drawing on training studies in non-athletes and in twin pairs, her research challenges the Morganroth hypothesis by showing that endurance training induces eccentric hypertrophy while resistance training produces limited or even reduced left ventricular mass. Naylor also presents case studies demonstrating that eccentric exercise and exercise gaming can restore strength and physical activity in patients recovering from heart failure.

Key Highlights

• As little as 15 minutes of physical activity each day is associated with a 14% reduction in all-cause mortality, and individuals performing some moderate to vigorous weekly exercise show significantly lower mortality regardless of cardiovascular risk factors such as hypertension and obesity, though very high volumes may slightly raise mortality risk alongside elevated markers of cardiomyocyte injury and cardiac fatigue.
• Crossover training studies in non-athletes and in twin pairs found that endurance training increased left ventricular mass through eccentric hypertrophy while resistance training produced limited or decreased mass, casting doubt on the Morganroth hypothesis derived from Olympic athlete cohorts that lacked scaling to body mass.
• Individual responses to identical exercise programs vary considerably, meaning patients who see limited benefit from one modality may achieve results by switching, and clinical case studies show that low cardiorespiratory demand eccentric exercise and exercise games such as Just Dance can restore strength and activity after heart failure and prolonged bed rest.

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Ep. 5: Androgens & Cardiovascular Diseases in Women: From Basic Research to Clinical Practice

September 14, 2022

Dr. Licy Yanes Cardozo, Professor in the Departments of Pharmacology and Medicine/Endocrinology at the University of Mississippi Medical Center, examines how androgen excess drives cardiometabolic disease in women with polycystic ovary syndrome and in transgender patients receiving hormone therapy. Combining clinical case studies with a PCOS mouse model, her research shows that hyperandrogenemia underlies obesity, insulin resistance, and elevated blood pressure while modulating the efficacy of diabetes pharmacotherapies, with peroxisome proliferator-activated receptor gamma identified as a key contributor to cardiometabolic complications. Yanes Cardozo also addresses geographic and ethnic disparities in PCOS presentation and the emerging cardiovascular effects of gender-affirming hormone therapy.

Key Highlights

• Polycystic ovary syndrome is the most common endocrine disorder in reproductive-age women, affecting roughly 10 to 20% of all women yet frequently going undiagnosed, with hyperandrogenemia driving the associated obesity, insulin resistance, and hypertension and modulating the responsiveness of therapies including metformin and the GLP-1 receptor agonist liraglutide.
• PCOS presentation varies by geography and ethnicity, with African American women showing higher blood pressure, hemoglobin A1C, and body mass index than Caucasian women from similar regions and Black women in Alabama exhibiting greater hirsutism and insulin resistance than Black women in California, pointing to social determinants of health reinforced by a positive feedback loop between hyperandrogenemia and obesity.
• Gender-affirming hormone therapy substantially improves mental health outcomes, with reduced anxiety and depression and quality of life improvements reported in 80% of participants, while cardiovascular effects diverge by direction of transition as transgender men experience increased systolic blood pressure and transgender women show the opposite.

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Ep. 6: Cardiac Research Using Microelectrode Array Technology: Methodology Considerations and Best Practices to Optimize Recording

September 21, 2022

Dr. George Portugal, Senior Applications Scientist at Harvard Bioscience, presents microelectrode array technology as a versatile platform for cardiac electrophysiology research using stem cell derived and primary cardiomyocytes. He reviews how networks of extracellular recording electrodes enable rapid compound screening, toxicological monitoring, and assessment of conduction velocity and arrhythmia across preparations ranging from cell culture to organoids, cardiac slices, and whole heart. Portugal addresses the methodological challenges of MEA recording and shares best practices to help laboratories integrate the technique efficiently. Sponsored by Harvard Bioscience.

Key Highlights

• Microelectrode array networks of extracellular recording electrodes allow investigators using stem cell derived or primary cardiomyocytes to rapidly screen compounds, monitor toxicological effects, and quantify changes in conduction velocity and arrhythmia.
• The same MEA technology scales across preparation types including cell culture, cardiac organoids, cardiac slices, and whole heart applications, with recording examples presented for each to illustrate the practical differences in setup and signal quality.
• Attention to specific methodological challenges and adoption of established best practices for MEA recording allows laboratories to optimize signal fidelity and integrate the technique as a new capability without extensive electrophysiology infrastructure.

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Ep. 7: Inflammation and Vascular Damage in Hypertension

September 28, 2022

Dr. Ana Briones, Professor of Pharmacology at the Universidad Autónoma de Madrid, examines how excessive inflammation from both innate and adaptive immune systems drives endothelial dysfunction, vascular remodeling, and arterial stiffening in hypertension. Her research shows that the inflammatory milieu in hypertensive vasculature arises not only from elevated proinflammatory cytokine production and oxidative stress but also from unresolved or inefficient resolution of inflammation. Briones presents novel proinflammatory mediators associated with vascular damage and discusses boosting the resolution of inflammation through specialized pro-resolving mediators as a new therapeutic approach for hypertension. Sponsored by Kent Scientific Corporation.

Key Highlights

• Inflammation is a common feature across cardiovascular diseases including atherosclerosis, aneurysms, obesity, and hypertension, with elevated local and circulating proinflammatory cytokines combining with oxidative stress to produce endothelial dysfunction, vascular remodeling, and augmented vascular stiffness.
• Failure to resolve inflammation, rather than cytokine overproduction alone, contributes to the sustained inflammatory environment in hypertensive vasculature, shifting attention from suppressing inflammatory signals to restoring the resolution phase.
• Specialized pro-resolving mediators including lipoxins, resolvins, protectins, and maresins limit immune cell infiltration and initiate tissue repair, making pharmacological enhancement of resolution a promising therapeutic strategy for hypertension and associated vascular alterations.

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Ep. 8: Cardiac Tissue Slices: Preparation, Data Acquisition, and Analysis

October 5, 2022

Dr. Bradley Palmer, CEO of Sarcometrics and Assistant Professor of Molecular Physiology and Biophysics at the University of Vermont, demonstrates the preparation and functional analysis of cardiac tissue slices, a model that preserves native myocardial architecture including both fibroblasts and myocytes while remaining amenable to measurements not feasible in whole heart studies. He walks through slice preparation technique alongside acquisition of force, calcium transients, work loops, and stress and strain data. Palmer's work applies these slices to mimic the pressure-volume relationship and identify molecular mechanisms of cardiac dysfunction in heart failure, diabetes, and hypertension. Sponsored by IonOptix.

Key Highlights

• Cardiac tissue slices occupy a useful middle ground between isolated cardiomyocytes and whole heart preparations, retaining native myocardial tissue with both fibroblast and myocyte populations while permitting acquisition of functional parameters such as calcium transients that whole heart studies cannot readily provide.
• Slice preparation remains the primary barrier to adoption in most laboratories, and the webinar demonstrates the technique step by step alongside setup for simultaneous force and calcium measurement, work loops, and stress and strain analysis.
• Cardiac slices configured to mimic the pressure-volume relationship allow investigators to detect and discern molecular mechanisms underlying cardiac dysfunction in pathological states including heart failure, diabetes, and hypertension, with data analysis and interpretation demonstrated throughout.

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Ep. 9: Cardiovascular Regenerative Medicine: Deconstructing Regenerative Therapeutics

October 12, 2022

Dr. Eduardo Marbán, Executive Director of the Smidt Heart Institute at Cedars-Sinai Medical Center and a pioneer in gene- and cell-based therapies for heart disease, deconstructs the mechanisms behind cardiovascular regenerative therapies to identify the active components responsible for their benefits. His laboratory has identified several noncoding RNA species, including short Y RNAs carried within extracellular vesicles, that exert biological actions on their own and can be used either in native form or as bioinspiration for new chemical entities. Marbán argues that next-generation cell-free biologics built from extracellular vesicles and noncoding RNAs may match or exceed the benefits of cell therapy while avoiding its intrinsic limitations.

Key Highlights

• Noncoding RNA species carried in extracellular vesicles, including short Y RNAs, possess intrinsic biological activity and can be deployed as they occur naturally or used as templates for entirely new synthetic chemical entities.
• Cell-free biologics based on extracellular vesicles and noncoding RNAs offer a path to match or transcend the therapeutic benefits of cell therapy while avoiding intrinsic limitations of live-cell products such as manufacturing complexity, engraftment failure, and immunogenicity.

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Ep. 10: Investigating a Novel Regulator of Atrial Contractility

October 19, 2022

Dr. David Barefield, Assistant Professor of Cell and Molecular Physiology at Loyola University Chicago, examines myosin binding protein H-like (MyBP-HL), an atrial myofilament protein that establishes stoichiometry with cardiac myosin binding protein-C and whose loss produces atrial dilation, arrhythmia, and dilated cardiomyopathy. His laboratory tested whether human MYBPHL nonsense variants catalogued in the gnomAD database prevent myofilament incorporation or instead redirect the truncated protein elsewhere in the cardiomyocyte, using transfected neonatal rat cardiomyocytes and immunofluorescence confocal microscopy. Barefield then applied biophysical measurements on single myofibrils from Mybphl null mice to establish the functional consequences of MyBP-HL loss for atrial contractility. Sponsored by Aurora Scientific.

Key Highlights

• MyBP-HL is an atrial-specific myofilament protein that maintains a defined stoichiometry with cardiac myosin binding protein-C, and its loss leads to atrial dilation, arrhythmia, and dilated cardiomyopathy, establishing it as a candidate regulator of atrial contractile function.
• Wild-type mouse MyBP-HL colocalized with cMyBP-C in transfected neonatal rat cardiomyocytes, while the human nonsense variants W54X, R133X, W158X, W192X, K250X, and R255X all failed to colocalize, indicating that MYBPHL premature stop variants do not encode functional myofilament-binding proteins.
• Single myofibrils isolated from Mybphl null mice exhibited a significantly faster linear phase of relaxation, demonstrating that loss of MyBP-HL produces measurable biophysical defects in atrial myofibril mechanics rather than acting solely through structural remodeling.

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Ep. 11: Cardiometabolic Disease Pathophysiology & Novel Therapies for Atherosclerosis & Calcification

October 26, 2022

Dr. Michael Sturek, Professor of Anatomy, Cell Biology, and Physiology at Indiana University, reviews the macrovascular atherosclerosis and microvascular dysfunction that underlie ischemic events and argues for appropriate large animal models to improve translation. His research demonstrates that intracellular calcium release predominates in healthy coronary smooth muscle cells but declines markedly in cells from metabolic syndrome swine and humans, implicating impaired lysosomal calcium signaling as an early trigger for extracellular hydroxyapatite crystal deposition. Sturek proposes that selective modulation of lysosomal calcium stores could alter autophagy and matrix vesicle release, offering a novel therapeutic route for coronary atherosclerosis and calcification.

Key Highlights

• Cardiometabolic disease continues to rise unabated and coronary heart disease remains the leading cause of death worldwide, with calcification persisting as a difficult clinical problem even as lipid lowering therapy effectively treats atherosclerosis.
• Statins and exercise both increase coronary artery calcification despite their overall cardiovascular benefit, and intracellular calcium release in coronary smooth muscle cells declines markedly in metabolic syndrome swine and humans, pointing to impaired lysosomal calcium signaling as an initiating event in extracellular hydroxyapatite deposition.
• Selective modulation of lysosomal calcium stores may alter autophagy and matrix vesicle release to treat coronary atherosclerosis and calcification, with metabolic syndrome swine models providing the physiological relevance needed for translation to human disease.

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Ep. 12: Advances in Pressure-Volume Loop Data Collection: Tools, Training and Support

November 2, 2022

Cole McLarty, Director of Sales and Marketing, and Nick Glover, Product Manager and Research Sales Specialist, both of the Transonic Systems Research Division, are joined by Dr. Timothy A. Hacker, Director of the Cardiovascular Physiology and Surgery Core Facility at the University of Wisconsin-Madison, for a technical overview of pressure-volume loop collection and analysis. The presenters introduce the ADV550 system, which allows users to position catheters with immediate blood volume feedback, addressing a longstanding technical obstacle in PV loop workflows. Hacker reviews his hands-on PV loop surgical workshop covering catheterization through data review, and the group announces a scholarship aimed at expanding training opportunities in the PV loop community. Sponsored by Transonic Systems.

Key Highlights

• Pressure-volume loops yield hemodynamic parameters that are otherwise difficult to measure, including contractility, elastance, power, energetics, and efficiency across both load-dependent and load-independent states, but carry substantial technical challenges during data collection.
• The ADV550 represents a next generation of PV loop technology built to streamline workflow by giving users immediate blood volume feedback during catheter positioning, reducing a common source of measurement error.
• An immersive surgical workshop led by Dr. Hacker, whose core facility has established cardiac disease models in mice, rats, rabbits, pigs, dogs, and primates, covers catheterization techniques through data review, and a new scholarship program aims to broaden access to PV loop training.

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Ep. 13: Cardio-Renal-Lymphatic Disease

November 9, 2022

Dr. Giacomo Rossitto, Assistant Professor and Consultant in Cardiovascular and Emergency Medicine at the Università degli Studi di Padova and Honorary Research Fellow at the University of Glasgow Institute of Cardiovascular and Medical Sciences, examines the often-overlooked role of the lymphatic system in cardiovascular disease and fluid homeostasis. His physiological studies indicate defective interstitial fluid drainage in patients with heart failure, a prototypic condition of overt extracellular volume expansion, where excess tissue sodium reflects a key and targetable determinant of disease. Rossitto discusses emerging evidence linking organ-specific lymphatic systems to organ function, with particular attention to the myocardium, the kidneys, and their interplay in maintaining fluid balance.

Key Highlights

• Excess tissue sodium is highly prevalent in cardiovascular disease and reflects clinical or subclinical extracellular volume expansion, making it a key and targetable determinant of disease progression rather than a passive marker.
• The lymphatic vasculature serves as the major route for draining fluids that continuously extravasate into the interstitium, and physiological studies in heart failure patients suggest this drainage capacity is defective, contributing directly to volume overload.
• Organ-specific lymphatic systems are increasingly linked to organ function, with the myocardial and renal lymphatics and their interplay emerging as central to fluid homeostasis and as potential therapeutic targets in cardio-renal disease.

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Ep. 14: Experimental Design Considerations to Optimize Chronic Cardiovascular Telemetry Studies

November 16, 2022

Dr. Phil Griffiths, Research Sales Manager for Europe at ADInstruments, who trained in neuroscience at the University of Bristol with expertise in in vivo blood pressure recording via telemetry, presents the practical considerations for designing chronic cardiovascular telemetry experiments. He reviews the physiological advantages of chronic recording over acute measurement approaches and addresses how to select appropriate sample sizes to ensure adequately powered studies. Griffiths also covers tips for data acquisition and handling alongside strategies to maintain high animal welfare standards throughout long-term telemetry protocols. Sponsored by ADInstruments.

Key Highlights

• Chronic telemetry studies yield more physiologically accurate cardiovascular data than acute preparations by allowing continuous recording in conscious, freely moving animals, but realizing that benefit depends on careful upfront planning and experimental design.
• Appropriate sample size selection is critical to chronic study success, ensuring adequate statistical power while avoiding unnecessary animal use in long-duration protocols.
• Practical approaches to data acquisition and handling, combined with attention to high animal welfare standards, together determine both the quality of telemetry datasets and the ethical soundness of chronic cardiovascular experiments.

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