Aged patients are susceptible to cellular stress events associated with surgery. Exosomes represent a new paradigm in the cellular stress response that has only recently begun to be addressed in the surgical population. Exosomes are released by cells in response to numerous stimuli including cell stress and carry a cargo of biologically active molecules including DNA, RNA, proteins, lipids, cytokines, growth factors and metabolites. The role of exosomes in the aging surgical population is unknown and may have major impact on perioperative care. Deep hypothermic circulatory arrest (DHCA) is a profound perioperative stress event involving isolation of the systemic vasculature via cardiopulmonary bypass and arrest of the circulation to major organ systems. There is no information available regarding the release of exosomes as a result of the stress of whole body ischemia and reperfusion after DHCA in patients and most importantly as a function of age. At the University of California, San Diego we perform DHCA in conjunction with pulmonary thromboendarterectomy (PTE) surgery. Our clinical volume of 200 PTE surgeries per year results in patients with a range of ages (18- 80 years old) undergoing DHCA. We will test the novel hypothesis that surgically induced DHCA increases the release of exosomes, alters the characteristics of the exosome profile, and alters the ability of exosomes to affect cellular metabolism and function in an age dependent manner. In the proposal we will: 1) Determine the characteristics and content of exosomes released from patients before and after DHCA and address the potential role of patient age on the release and content of exosomes, and 2) Assess the potential of exosomes released from different age groups in response to DHCA to affect metabolism and function in human endothelial cells. The work will combine expertise from anesthesia, surgery, medicine and basic science disciplines and promote the future investigation of innovative hypotheses and novel therapies for the organismal response to ischemia-reperfusion injury in aged patients.

Public Health Relevance

Aged patients are susceptible to the profound cellular stress events associated with surgery. We will use our unique surgical population at our institution to explore the release of biological substances known as exosomes into the circulation of young and aged patients after whole body ischemia and surgical deep hypothermic circulatory arrest. The work has potential to open new avenues for therapeutics and biomarkers in aged patients undergoing surgery.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG058174-01A1
Application #
9601388
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Kerr, Candace L
Project Start
2018-09-01
Project End
2020-06-30
Budget Start
2018-09-01
Budget End
2019-06-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093