Impact of early pericardial fluid chymase activation after cardiac surgery

Brittany Butts; Lee A. Goeddel; Jingyi Zheng; Betty Pat; Betty Pat; Pamela Powell; Pamela Powell; James Mobley; Sarfaraz Ahmad; Chad Steele; David McGiffin; James E. Davies; James F. George; Spencer J. Melby; Spencer J. Melby; Carlos M. Ferrario; Louis J. Dell’Italia; Louis J. Dell’Italia

doi:10.3389/fcvm.2023.1132786

Frontiers in Cardiovascular Medicine (Apr 2023)

Impact of early pericardial fluid chymase activation after cardiac surgery

Brittany Butts,
Lee A. Goeddel,
Jingyi Zheng,
Betty Pat,
Betty Pat,
Pamela Powell,
Pamela Powell,
James Mobley,
Sarfaraz Ahmad,
Chad Steele,
David McGiffin,
James E. Davies,
James F. George,
Spencer J. Melby,
Spencer J. Melby,
Carlos M. Ferrario,
Louis J. Dell’Italia,
Louis J. Dell’Italia

Affiliations

Brittany Butts: Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, United States
Lee A. Goeddel: Department of Anesthesia and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United States
Jingyi Zheng: Department of Mathematics and Statistics, College of Science and Mathematics, Auburn University, Auburn, AL, United States
Betty Pat: Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham (UAB), Birmingham, AL, United States
Betty Pat: Department of Veterans Affairs, Birmingham Veterans Affairs Health Care System, Birmingham, AL, United States
Pamela Powell: Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham (UAB), Birmingham, AL, United States
Pamela Powell: Department of Veterans Affairs, Birmingham Veterans Affairs Health Care System, Birmingham, AL, United States
James Mobley: Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, United States
Sarfaraz Ahmad: Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC, United States
Chad Steele: School of Medicine—Microbiology and Immunology, Tulane University, New Orleans, LA, United States
David McGiffin: Cardiothoracic Surgery and Transplantation, The Alfred Hospital, Monash University, Melbourne, VIC, Australia
James E. Davies: 0Department of Surgery, Division of Cardiothoracic Surgery, University of Alabama at Birmingham (UAB), Birmingham, AL, United States
James F. George: 0Department of Surgery, Division of Cardiothoracic Surgery, University of Alabama at Birmingham (UAB), Birmingham, AL, United States
Spencer J. Melby: 1Department of Surgery, Division of Cardiothoracic Surgery, Washington University, Saint Louis, MO, United States
Spencer J. Melby: 2Saint Louis VA Medical Center, Birmingham VA Health Care System, Birmingham, AL, United States
Carlos M. Ferrario: Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC, United States
Louis J. Dell’Italia: Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham (UAB), Birmingham, AL, United States
Louis J. Dell’Italia: Department of Veterans Affairs, Birmingham Veterans Affairs Health Care System, Birmingham, AL, United States

DOI: https://doi.org/10.3389/fcvm.2023.1132786
Journal volume & issue: Vol. 10

Abstract

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IntroductionChymase is a highly destructive serine protease rapidly neutralized in the circulation by protease inhibitors. Here we test whether pericardial fluid (PCF) chymase activation and other inflammatory biomarkers determine intensive care unit length of stay, and explore mechanisms of chymase delivery by extracellular vesicles to the heart.MethodsPCF was collected from adult patients (17 on-pump; 13 off-pump) 4 h after cardiac surgery. Extracellular vesicles (EVs) containing chymase were injected into Sprague–Dawley rats to test for their ability to deliver chymase to the heart.ResultsThe mean intensive care unit (ICU) stay and mean total length of stay was 2.17 ± 3.8 days and 6.41 ± 1.3 days respectively. Chymase activity and 32 inflammatory markers did not differ in on-pump vs. off-pump cardiac surgery. Society of Thoracic Surgeons Predicted Risk of Morbidity and Mortality Score (STS-PROM), 4-hour post-surgery PCF chymase activity and C-X-C motif chemokine ligand 6 (CXCL6) were all independent predictors of ICU and total hospital length of stay by univariate analysis. Mass spectrometry of baseline PCF shows the presence of serine protease inhibitors that neutralize chymase activity. The compartmentalization of chymase within and on the surface of PCF EVs was visualized by immunogold labeling and transmission electron microscopy. A chymase inhibitor prevented EV chymase activity (0.28 fmol/mg/min vs. 14.14 fmol/mg/min). Intravenous injection of PCF EVs obtained 24 h after surgery into Sprague Dawley rats shows diffuse human chymase uptake in the heart with extensive cardiomyocyte damage 4 h after injection.DiscussionEarly postoperative PCF chymase activation underscores its potential role in cardiac damage soon after on- or off-pump cardiac surgery. In addition, chymase in extracellular vesicles provides a protected delivery mechanism from neutralization by circulating serine protease inhibitors.

Published in Frontiers in Cardiovascular Medicine

ISSN: 2297-055X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.frontiersin.org/journals/cardiovascular-medicine

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