Grant: Discovery Grants Program - Individual

The heart, circulation, lungs, and chest wall act together in a highly coordinated fashion. While studying each system in isolation can provide valuable information, examining how these systems work together provides a more comprehensive understanding of basic physiology. My program seeks to further our understanding of the anatomic and physiological relationships between these systems using a human model. Biological sex has been rarely considered when exploring cardiorespiratory interactions however, important differences have now been identified. For example, skeletal muscle fatigability differs between the sexes. Women are usually less fatigable than men during single-limb contractions but little is known about sex differences in the fatigability of the respiratory musculature. The LONG-TERM OBJECTIVE of my program is to understand how the cardiovascular and respiratory systems interact and adapt to physiological challenges. My SHORT-TERM OBJECTIVES build upon recent progress along four specific aims. Aim 1 seeks to understand how the respiratory muscles compete for oxygen delivery. Participants will perform exercise while the respiratory musculature is manipulated experimentally with a unique ventilator and blood flow to the exercising limbs will be measured directly. Aim 2 will determine the effect of respiratory muscle work on sympathetic vasoconstrictor outflow and blood pressure during exercise. Continuous measures of nerve activity will be acquired to provide an understanding of the neural consequences of breathing. Aim 3 will use novel imaging methodologies to quantify male and female airways. Coupling in vivo airway measures with lung mechanics during exercise permits a comprehensive assessment of the relationship between airway structure and physiological function. Aim 4 will determine if respiratory muscle fatigue differs between the sexes. To assess the independent effect of respiratory muscle contraction participants will perform high intensity contractions of the diaphragm against high airway resistance. Diaphragm fatigue will be assessed using magnetic stimulation of the phrenic nerves. Each aim is designed such that they provide a significant training opportunity for HQP ranging from undergraduates to postdoctoral fellows. Novel methods and integrative experimental approaches will provide mechanistic knowledge of how the human respiratory system influences cardiovascular control a relationship that is not well understood.