Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Sepsis is a severe clinical syndrome caused by an abnormal inflammatory response to an infectious agent. It is a major cause of death in intensive care units and approximately 28% of patients that develop sepsis will succumb to the disease, accounting for over 9% of deaths in the United States annually. Septic shock is a common feature of severe sepsis that is characterized by a rapid decrease in blood pressure. Septic shock limits oxygen supply to the tissues and is therefore thought to promote multiple organ failure and subsequent death in patients with sepsis. The sympathetic nervous system (SNS) functions to maintain blood pressure during both normal and pathological states. Adrenal chromaffin cells (ACCs) are key components of the SNS that secrete signaling molecules, known as catecholamines, into the bloodstream where they alter many functions, including blood flow. During sepsis, there is an elevation in circulating catecholamines, which may play a protective role by dampening the inflammatory response and helping maintain blood pressure. Furthermore, sepsis patients are often treated with substances that mimic catecholamines to enhance blood flow to the tissues. Given the significant role that catecholamines play in the course and treatment of sepsis, it is important to understand the underlying mechanisms responsible for their enhanced secretion. There is evidence that alterations in ACC function may contribute to the elevated catecholamine secretion observed during sepsis. However, these changes have yet to be directly examined. During the tenure of this award, I plan to investigate how ACCs are altered during the course of sepsis. These experiments will provide important insights into the mechanisms responsible for elevated catecholamine secretion during sepsis, and may shed light on novel therapeutic strategies that can optimize catecholamine secretion to maintain oxygen supply to the tissues.