Bioactive Oxylipins in Infants and Children With Congenital Heart Disease Undergoing Pediatric Cardiopulmonary Bypass
Authors: Kim-Campbell Nahmah , Gretchen Catherine , Ritov Vladimir B. , Kochanek Patrick M. , Balasubramani Goundappa K. , Kenny Elizabeth , Sharma Mahesh , Viegas Melita , Callaway Clifton , Kagan Valerian E. , Bayír Hülya 
Published: July 2019

Objectives:
To determine the production of 9-hydroxyoctadecadienoic acid and 13-hydroxyoctadecadienoic acid during cardiopulmonary bypass in infants and children undergoing cardiac surgery, evaluate their relationship with increase in cell-free plasma hemoglobin, provide evidence of bioactivity through markers of inflammation and vasoactivity (WBC count, milrinone use, vasoactive-inotropic score), and examine their association with overall clinical burden (ICU/hospital length of stay and mechanical ventilation duration).

Design:
Prospective observational study.

Setting:
Twelve-bed cardiac ICU in a university-affiliated children’s hospital.

Patients:
Children were prospectively enrolled during their preoperative clinic appointments with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass

Interventions:
None.

Measurements and Main Results:
Plasma was collected at the start and end of cardiopulmonary bypass in 34 patients. 9-hydroxyoctadecadienoic acid, 13-hydroxyoctadecadienoic acid, plasma hemoglobin, and WBC increased. 9:13-hydroxyoctadecadienoic acid at the start of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2–24 hours postcardiopulmonary bypass (R
2 = 0.25; p < 0.01), milrinone use (R
2 = 0.17; p < 0.05), and WBC (R
2 = 0.12; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the end of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2–24 hours (R
2 = 0.17; p < 0.05), 24–48 hours postcardiopulmonary bypass (R
2 = 0.12; p < 0.05), and milrinone use (R
2 = 0.19; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the start and end of cardiopulmonary bypass were associated with the changes in plasma hemoglobin (R
2 = 0.21 and R
2 = 0.23; p < 0.01). The changes in plasma hemoglobin was associated with milrinone use (R
2 = 0.36; p < 0.001) and vasoactive-inotropic score less than 2 hours (R
2 = 0.22; p < 0.01), 2–24 hours (R
2 = 0.24; p < 0.01), and 24–48 hours (R
2 = 0.48; p < 0.001) postcardiopulmonary bypass. Cardiopulmonary bypass duration, 9:13-hydroxyoctadecadienoic acid at start of cardiopulmonary bypass, and plasma hemoglobin may be risk factors for high vasoactive-inotropic score. Cardiopulmonary bypass duration, changes in plasma hemoglobin, 9:13-hydroxyoctadecadienoic acid, and vasoactive-inotropic score correlate with ICU and hospital length of stay and/mechanical ventilation days.

Conclusions:
In low-risk pediatric patients undergoing cardiopulmonary bypass, 9:13-hydroxyoctadecadienoic acid was associated with changes in plasma hemoglobin, vasoactive-inotropic score, and WBC count, and may be a risk factor for high vasoactive-inotropic score, indicating possible inflammatory and vasoactive effects. Further studies are warranted to delineate the role of hydroxyoctadecadienoic acids and plasma hemoglobin in cardiopulmonary bypass-related dysfunction and to explore hydroxyoctadecadienoic acid production as a potential therapeutic target.