Grant: Discovery Grants Program - Individual

The heart, circulation, lungs, and chest wall act together in a highly coordinated fashion. A change to one system results in a change to the other. How it is the different systems interact under biologically relevant conditions is complex and not fully understood. My program seeks to further our understanding of the anatomic and physiological relationships between these organ systems using a human model. Traditionally, biological sex has rarely been considered when exploring cardiorespiratory interactions leading to a significant knowledge gap; however, important sex-differences have recently been identified. The LONG-TERM OBJECTIVES of my program are: to understand how the human respiratory and cardiovascular systems interact, respond and adapt to physiological stressors, and identify potential sex-based differences and explain the mechanistic basis for them. My approach explores the integration of the respiratory and cardiovascular systems to provide a framework to better understand biological complexities. Three SHORT-TERM OBJECTIVES that build upon recent progress will inform my long-term goals. The first objective is to determine how the respiratory system influences the distribution of blood flow during exercise. To accomplish this a novel ventilator has been created that can manipulate the respiratory system during exercise. We will measure how the nervous system controls how much blood needs to be directed towards working muscle. The second objective seeks to understand how sex-differences in airway anatomy can influence how the muscles of breathing contract. To accomplish this, we will use innovative imaging methodologies to quantify male and female airways. Coupling complex airway measures with lung mechanics during exercise permits a comprehensive assessment of the relationship between airway structure and physiological function. This approach is unique and will provide measures that have, to date, not been possible to acquire. The third objective seeks to understand the effects of healthy aging and biological sex on how it is the heart and lung interact. Aging is associated with a progressive decline in pulmonary structure and function. While much is known about exercise, aging and the lung, the interactions between the biology of aging and sex-based differences in pulmonary structure and function are not fully understood. Studying isolated organ systems provides valuable information but examining how these systems work together provides a more detailed understanding of basic physiology. The proposed work will create a stimulating training environment where each objective is designed such that they provide a significant training opportunity for HQP ranging from undergraduates to postdoctoral fellows. Original methods and integrative experimental approaches will provide foundational knowledge of how the human respiratory system influences cardiovascular control and why this may differ on the basis of biological sex.