Bioactive Oxylipins in Infants and Children With Congenital Heart Disease Undergoing Pediatric Cardiopulmonary Bypass

Abstract

Objective: To determine the production of 9-hydroxyoctadecadienoic acid (9-HODE) and 13hydroxyoctadecadienoic acid (13-HODE) during cardiopulmonary bypass (CPB) in infants and children undergoing cardiac surgery, evaluate their relationship with increase in cell-free plasma hemoglobin (PHb), provide evidence of bioactivity through markers of inflammation and vasoactivity (WBC count, milrinone use, vasoactive inotropic score [VIS]), and examine their association with overall clinical burden (ICU/hospital LOS and mechanical ventilation duration) Design: Prospective observational studySetting: 12-bed cardiac ICU in a university-affiliated children's hospital Patients: Children were prospectively enrolled during their pre-operative clinic appointments with the following criteria: >1month to <18 years old, procedures requiring CPB Interventions: NoneMeasurements and Main Results: Plasma was collected at the start (StartCPB) and end of CPB (EndCPB) in 34 patients. 9-HODE, 13-HODE, PHb, and WBC increased. 9:13-HODE at StartCPB was associated with VIS at 2-24h post-CPB (R 2 =0.25, p<.01), milrinone use (R 2 =0.17, p<.05), and WBC (R 2 =0.12, p<.05). 9:13-HODE at EndCPB was associated with VIS at 2-24h (R 2 =0.17, p<.05) and 24-48h post-CPB (R 2 =0.12, p<.05) and milrinone use (R 2 =0.19, p<.05).

Association Between Hyperoxemia and Increased Cell-Free Plasma Hemoglobin During Cardiopulmonary Bypass in Infants and Children*

“…During CPB, the continuous exposure of the RBC to ROS can lead to lipid peroxidation of polyunsaturated fatty acids found in the RBC cell membrane, oxidation of amino acid residue side chains and the protein backbone, crosslinking of membrane proteins, generation of protein oxidation products, and destabilization of the cytoskeletal protein interaction (17). We have found previously that the level of products of lipid oxidation increase during CPB and is associated with CPB duration, which suggests an exposure timedependence of this effect (14). Alterations to membrane and cytoskeletal proteins can lead to impaired deformability that would likely increase their susceptibility to the mechanical stress produced by a CPB circuit.…”

“…As a hemeprotein, PHb’s role in oxidative stress lies, in part, in its peroxidase activity (8). When unregulated, it can lead to the consumption of antioxidants, the accumulation of oxidation products, and the detrimental end-organ effects seen in both pediatric and adult CPB (13, 14).…”

The Year in Review: Anesthesia for Congenital Heart Disease 2019

“…The ratio of 9:13 HODE at the start of CPB was associated with milrinone use (R 2 ¼ 0.17; P < .05), VIS (R 2 ¼ 0.25; P < .01), increase in white blood cell count (R 2 ¼ 0.12; P < .05), and DPHb (R 2 ¼ 0.21; P < .01). 6 CPB time, DPHb, and increased 9:13 HODE at the start of CPB were identified as risk factors for elevated VIS and correlated with LOS and mechanical ventilation days. 6 Several articles examined pro-inflammatory biomarkers as predictors of postoperative outcomes.…”

“…6 CPB time, DPHb, and increased 9:13 HODE at the start of CPB were identified as risk factors for elevated VIS and correlated with LOS and mechanical ventilation days. 6 Several articles examined pro-inflammatory biomarkers as predictors of postoperative outcomes. Bobillo-Perez et al performed a prospective study of 111 children undergoing CPB who required ICU admission postoperatively.…”

Fifty Years of Critical Care Medicine: The Editors’ Perspective

“…By my final year as Editor-in-Chief in 2020, the content had evolved. For example, the January issue that year included a report on 250 children studied at 39 sites by the prolific National Institutes of Health (NIH)-funded multicenter Therapeutic Hypothermia after Pediatric Cardiac Arrest trials group; a report on a social network analysis of co-authorship of 400 recent randomized controlled trials in our field, a report on the application of the Cornell Assessment of Pediatric Delirium score in over 2,400 children, two NIH-funded reports on cardiopulmonary bypass in children, and a report on acute kidney injury in over 1,000 children in a Canadian PICU (28−33).…”