Clinical cardiovascular diseases
Our work on clinical cardiovascular diseases focuses mainly on physiologic mechanisms in people receiving care for heart failure, pulmonary arterial hypertension and other conditions.
We hope to increase scientific understanding of key physiologic mechanisms so that our team can develop robust diagnosis and treatment techniques, including options for ongoing COVID-19 symptoms.
Respiratory physiology of persistent COVID-19 symptoms
Many people who had COVID-19 have residual symptoms for months or longer, which is sometimes called post-COVID-19 syndrome or long covid. Long COVID often affects the respiratory system, which impacts numerous other organ systems, including the brain, the heart and the immune system.
Our lab has 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. We've developed several novel methods that have been reported to be key to some elements of the pathophysiology of COVID-19.
Mechanisms of altered ventilatory control in heart failure
Exercise intolerance is a hallmark of chronic heart failure. 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 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 research, we're using fentanyl to block the locomotor muscles' afferent feedback resulting from metabolic demand. We hope to determine if this will improve ventilatory efficiency, increase leg blood flow and improve exercise intolerance in people 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 people 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're using CT perfusion imaging to monitor a bolus of injected contrast as it moves through blood vessels to quantify and define intrathoracic fluid subdivisions.
We're 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. The results are being 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 are associated with interstitial edema or changes in blood volume compartments. There's also conflicting evidence whether pulmonary congestion occurs in heart failure in response to exercise and whether altered ventilatory patterns and gas exchange associated with heart failure help cause edema.
The goal of this study is to help resolve such uncertainties.
Hospital heart failure admission study
In this study, we're using a simplified approach to measure heart rate variability, pulmonary gas exchange and thoracic fluid status. This approach is being used in people as early as possible in the course of acute decompensated heart failure and immediately before discharge — after medical management.
Our objective is to determine if these measures — either absolute values or changes over the course of hospitalization — can assess readiness for discharge and predict the likelihood of readmission more accurately than can current methods.
Work and cost of breathing in heart failure
The objective of this research project is to use several techniques to characterize cost of breathing in people with heart failure. This includes 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
This work examines 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. We hope 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 hospitalized for concerns related to heart failure 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 people 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.