Clinical Cardiovascular Diseases Program
Many projects in the Clinical Cardiovascular Diseases Program within the Human Integrative and Environmental Physiology Laboratory focus on exploring physiologic mechanisms related to chronic disease in clinical populations, including patients with heart failure and pulmonary arterial hypertension.
The objective of the Clinical Cardiovascular Diseases Program is to increase the understanding of key physiologic mechanisms so that our team can develop robust diagnosis and treatment techniques, including options for ongoing COVID-19 symptoms.
The Clinical Cardiovascular Diseases Program has several ongoing studies and projects.
Respiratory physiology of persistent COVID-19 symptoms
Many patients who had COVID-19 continue to have residual symptoms and are sometimes known as "long haulers." While post-COVID symptoms are diverse, they often affect the respiratory system, which is central to the body and impacts numerous other organ systems, including the brain, heart and immune system.
Our laboratory has developed several novel methods that have been reported to be key to some of the pathophysiology of COVID-19. We have been studying people recovering from COVID-19 to try to better understand the relationship of their clinical course and demographic background to their residual symptoms and respiratory physiology.
Mechanisms of altered ventilatory control in heart failure
Exercise intolerance is a hallmark of chronic heart failure, and changes in cardiac function can cause systemic changes in the pulmonary system and skeletal muscles. One consequence of these systemic changes is an abnormal ventilatory response to exercise, which is believed to be a primary cause of dyspnea and exercise intolerance.
Our research team previously demonstrated that metabolic stimuli in the locomotor muscles play a major role in contributing to these exaggerated ventilatory responses to exercise. We found that the heightened ventilation in heart failure leads to blood flow redistribution away from the working muscles and may contribute to exercise intolerance.
In this study of altered ventilatory control, we are using fentanyl to block the locomotor muscles' afferent feedback resulting from metabolic demand to determine if this will improve ventilatory efficiency, increase leg blood flow and improve exercise intolerance in patients with heart failure.
Spinal cord stimulation to inhibit somatic afferent feedback during exercise
This project builds off the fentanyl heart failure study. If improvements in exercise tolerance are seen in patients with heart failure when given a fentanyl injection, use of spinal simulation may be a more feasible means of blockading this afferent feedback.
This study aims to determine the optimized stimulation intensity for this application of spinal cord stimulation.
Pulmonary congestion in heart failure
To study pulmonary congestion in heart failure, we are using CT perfusion imaging to follow a bolus of injected contrast as it moves through blood vessels to quantify and define intrathoracic fluid subdivisions.
We are also determining the effects of body position on shifts in intrathoracic fluid compartments and the influence on lung mechanics and gas exchange in people with heart failure compared with healthy people of the same age and sex.
Although pulmonary congestion has become an important target for detection and therapy in heart failure, it is neither well defined nor well understood. For instance, it's unclear if pulmonary congestion includes changes in thoracic blood volume, pulmonary blood volume, bronchial blood volume or extravascular lung water, or a combination of changes in these intrathoracic fluid compartments.
It's also unclear if the symptoms of positional dyspnea (orthopnea) are associated with interstitial edema or changes in blood volume compartments. There's also conflicting evidence as to whether pulmonary congestion occurs in heart failure in response to exercise and whether altered ventilatory patterns and gas exchange associated with heart failure contribute to the development of edema.
The goal of this study is to help resolve such uncertainties about pulmonary congestion in heart failure.
Hospital heart failure admission study
In this study, we use a simplified approach to measure heart rate variability, pulmonary gas exchange and thoracic fluid status in patients as early as possible in the course of acute decompensated heart failure and immediately prior to discharge (after medical management).
The objective is to determine if these measures (either absolute values or changes over the course of hospitalization) can assess readiness for discharge and predict likelihood of readmission more accurately than can current methods.
Work and cost of breathing in heart failure
The objective of this project is to characterize cost of breathing in patients with heart failure using several different techniques: gold standard pneumotach breathing versus camera-equipped systems that use sensor technology to reconstruct the thoracic cavity and model breathing mechanics.
Influence of beta-2 receptor genotype on lung fluid balance in heart failure
The focus of this project is to explore alterations in lung fluid balance in patients with heart failure and in matched healthy participants in response to administration of albuterol, a beta-2 agonist, and to determine if the response to albuterol is related to common polymorphisms of the beta-2 adrenergic receptors (β2ARs).
Lung fluid balance is measured using noncontrast chest CT and diffusion capacity of the lungs from carbon monoxide and nitric oxide.
Gaining a better understanding of the mechanisms of lung fluid accumulation and removal is important for disease management. For example, we found that 67% of patients admitted to the hospital for heart failure-related problems had signs of pulmonary edema as determined by chest X-ray.
Stimulation of the β2AR improves fluid clearance from the lungs in healthy adults through downstream activation of epithelial sodium channels on type II alveolar cells.
In patients with heart failure, however, chronic stimulation of the β2AR via increased adrenergic drive may lead to desensitization of these receptors in the lungs, altering this important clearance mechanism. In addition, the gene that encodes the β2AR has common variations that influence the degree of susceptibility to agonist-mediated desensitization and basal receptor activity.