Angiotensin-converting enzyme inhibition alters the inflammatory and fibrinolytic response to cardiopulmonary bypass in children.
OBJECTIVE
Many children with a congenital heart defect undergo surgical correction requiring cardiopulmonary bypass. One-sixth of these patients take an angiotensin-converting enzyme inhibitor for heart failure treatment. The effect of angiotensin-converting enzyme inhibition on the fibrinolytic and inflammatory response in children undergoing cardiopulmonary bypass is unknown. In adults, angiotensin-converting enzyme inhibition attenuates the increase in plasminogen activator inhibitor-1 after cardiopulmonary bypass, whereas the effect on the interleukin-6 response is uncertain. This study tests the hypothesis that preoperative angiotensin-converting enzyme inhibition attenuates postoperative plasminogen activator inhibitor-1 and interleukin-6 expression after cardiopulmonary bypass in children.


METHODS
Single-center prospective, randomized, nonblinded study.


METHODS
University-affiliated pediatric hospital.


METHODS
Children undergoing elective surgical correction of a congenital heart defect requiring cardiopulmonary bypass and taking an angiotensin-converting enzyme inhibitor.


METHODS
Children were randomized to continue angiotensin-converting enzyme inhibitor until the morning of surgery (angiotensin-converting enzyme inhibitor group, n = 11) or to discontinue therapy 72 hrs before surgery (no angiotensin-converting enzyme inhibitor group, n = 9).


RESULTS
Blood samples were collected at baseline before cardiopulmonary bypass, at 30 mins of cardiopulmonary bypass, on arrival to the intensive care unit, and on postoperative day 1. Baseline bradykinin concentrations were significantly higher and angiotensin-converting enzyme activity significantly lower in the angiotensin-converting enzyme inhibitor group compared with the no angiotensin-converting enzyme inhibitor group (p = .04 and .001, respectively). Plasminogen activator inhibitor-1 antigen increased 15-fold after cardiopulmonary bypass and peaked on postoperative day 1 (from 4.6 ± 1.2 to 67.7 ± 9.5 ng/mL; p < .001). Postoperative day 1 plasminogen activator inhibitor-1 antigen correlated significantly with cardiopulmonary bypass time (r2 = 0.40, p = .03) and was significantly lower in the angiotensin-converting enzyme inhibitor group compared with the no angiotensin-converting enzyme inhibitor group (p = .03). The proinflammatory markers interleukin-6 and interleukin-8 as well as the anti-inflammatory marker interleukin-10 increased significantly after cardiopulmonary bypass (all p < .001). Interleukin-6 concentrations were significantly higher in the angiotensin-converting enzyme inhibitor group after cardiopulmonary bypass (p = .02) even after controlling for potential confounding factors such as age, cardiopulmonary bypass time, and transfusion volume.


CONCLUSIONS
Angiotensin-converting enzyme inhibition attenuates the increase in postoperative plasminogen activator inhibitor-1 but enhances the interleukin-6 response in children undergoing cardiopulmonary bypass.
Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical School, Nashville, TN, USA.
Gregory A
GA
Fleming
Frederic T
FT
Billings
Tom M
TM
Klein
David P
DP
Bichell
Karla G
KG
Christian
Mias
M
Pretorius
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002675:Child, Preschool; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006330:Heart Defects, Congenital / Q000601:surgery; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D011183:Postoperative Complications / Q000517:prevention & control; D011446:Prospective Studies
D000806:Angiotensin-Converting Enzyme Inhibitors