Sean M Lang1, Mansoor A Syed2, James Dziura3, Edward Rocco4, Paul Kirshbom5, Vineet Bhandari2, John S Giuliano6. 1. Department of Pediatrics, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 2. Department of Pediatrics, Division of Perinatal Medicine, Yale University School of Medicine, New Haven, Connecticut. 3. Yale Center for Analytical Sciences, Yale University School of Medicine, New Haven, Connecticut. 4. Department of Perfusion, Division of Cardiothoracic Surgery, Yale-New Haven Hospital, New Haven, Connecticut. 5. Department of Cardiothoracic Surgery, Division of Pediatric Cardiothoracic Surgery, Yale University School of Medicine, New Haven, Connecticut. 6. Department of Pediatrics, Division of Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut. Electronic address: john.giuliano@yale.edu.
Abstract
BACKGROUND: Cardiopulmonary bypass subjects patients' blood to hemodilution and nonphysiologic conditions, resulting in a systemic inflammatory response. Modified ultrafiltration (MUF) counteracts hemodilution and has also been postulated to improve outcomes by proinflammatory cytokine removal. The objective of this study was to investigate whether the benefits of MUF include the removal of proinflammatory mediators, such as angiopoietin-2 (angpt-2). We hypothesize that some of the clinical benefits of MUF are related to the preferential removal of angpt-2. METHODS: We performed a prospective cohort study in children 18 years old or younger undergoing cardiopulmonary bypass. Serum samples were obtained from each patient preoperatively, after cardiopulmonary bypass, and on intensive care unit admission. A fluid sample from the MUF effluent was also analyzed. Angpt-1, angpt-2, interleukin-8, and interleukin-10 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Thirty-one patients were enrolled. Angpt-1 levels significantly decreased across all time points (p<0.01). Angpt-2 concentrations were significantly elevated at intensive care unit admission when compared with both preoperative and post-cardiopulmonary bypass levels (p<0.01). The angpt-2:1 ratio significantly increased after cardiopulmonary bypass to intensive care unit admission (p<0.01). There was no significant difference between the angpt-2 or angpt-1 percentage of extraction within MUF effluent. Interleukin-8 and interleukin-10 significantly increased from preoperative to intensive care unit admission (both p<0.01). CONCLUSIONS: The results of this study demonstrate that MUF removes both proinflammatory and antiinflammatory mediators equally. This study suggests that the clinical benefits of MUF cannot be attributed to the removal of larger quantities of proinflammatory mediators such as angpt-2 and interleukin-8.
BACKGROUND: Cardiopulmonary bypass subjects patients' blood to hemodilution and nonphysiologic conditions, resulting in a systemic inflammatory response. Modified ultrafiltration (MUF) counteracts hemodilution and has also been postulated to improve outcomes by proinflammatory cytokine removal. The objective of this study was to investigate whether the benefits of MUF include the removal of proinflammatory mediators, such as angiopoietin-2 (angpt-2). We hypothesize that some of the clinical benefits of MUF are related to the preferential removal of angpt-2. METHODS: We performed a prospective cohort study in children 18 years old or younger undergoing cardiopulmonary bypass. Serum samples were obtained from each patient preoperatively, after cardiopulmonary bypass, and on intensive care unit admission. A fluid sample from the MUF effluent was also analyzed. Angpt-1, angpt-2, interleukin-8, and interleukin-10 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Thirty-one patients were enrolled. Angpt-1 levels significantly decreased across all time points (p<0.01). Angpt-2 concentrations were significantly elevated at intensive care unit admission when compared with both preoperative and post-cardiopulmonary bypass levels (p<0.01). The angpt-2:1 ratio significantly increased after cardiopulmonary bypass to intensive care unit admission (p<0.01). There was no significant difference between the angpt-2 or angpt-1 percentage of extraction within MUF effluent. Interleukin-8 and interleukin-10 significantly increased from preoperative to intensive care unit admission (both p<0.01). CONCLUSIONS: The results of this study demonstrate that MUF removes both proinflammatory and antiinflammatory mediators equally. This study suggests that the clinical benefits of MUF cannot be attributed to the removal of larger quantities of proinflammatory mediators such as angpt-2 and interleukin-8.
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