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(Circulation. 1999;100:749-755.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

L-Arginine and Substance P Reverse the Pulmonary Endothelial Dysfunction Caused by Congenital Heart Surgery

Ingram Schulze-Neick, MD; Daniel J. Penny, MD; Michael L. Rigby, MD; Cliff Morgan, MD; Andrea Kelleher, MD; Peter Collins, MD; Jia Li, MD; Andrew Bush, MD; Elliot A. Shinebourne, MD; Andrew N. Redington, MD

From the Departments of Paediatrics (I.S.-N., D.J.P., M.L.R., J.L., A.B., E.A.S., A.N.R.), Anaesthesiology (C.M., A.K.), and Cardiology (P.C.), The Royal Brompton and Harefield NHS Trust and The National Heart and Lung Institute (Imperial College of Science, Technology and Medicine), London, UK.

Correspondence to Professor A.N. Redington, Department of Paediatric Cardiology, Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK. E-mail reding{at}ibm.net

Background—The increase in pulmonary vascular resistance (PVR) seen in children after cardiopulmonary bypass has been attributed to transient pulmonary endothelial dysfunction (PED). We therefore examined PED in children with congenital heart disease by assessing the L-arginine–nitric oxide (NO) pathway in terms of substrate supplementation (L-arginine [L-Arg]), stimulation of endogenous NO release (substance P [Sub-P]), and end-product provision (inhaled NO) before and after open heart surgery.

Methods and Results—Ten patients (aged 0.62±0.27 years) with pulmonary hypertension undergoing cardiac catheterization who had not had surgery and 10 patients (aged 0.65±0.73 years) who had recently undergone cardiopulmonary bypass were examined. All were sedated and paralyzed and received positive-pressure ventilation. Blood samples and pressure measurements were taken from catheters in the pulmonary artery and the pulmonary vein or left atrium. Respiratory mass spectrometry was used to measure oxygen uptake, and cardiac output was determined by the direct Fick method. PVR was calculated during steady state at ventilation with room air, during FIO₂ of 0.65, then during additional intravenous infusion of L-Arg (15 mg · kg^-1 · min^-1) and Sub-P (1 pmol · kg^-1 · min^-1), and finally during inhalation of NO (20 ppm). In preoperative patients, the lack of an additional significant change of PVR with L-Arg, Sub-P, and inhaled NO suggests little preexisting PED. Postoperative PVR was higher, with an additional pulmonary endothelial contribution that was restorable with L-Arg and Sub-P.

Conclusions—Postoperatively, the rise in PVR suggested PED, which was restorable by L-Arg and Sub-P, with no additional effect of inhaled NO. These results may indicate important new treatment strategies for these patients.

Key Words: endothelium • hypertension, pulmonary • amino acids • heart disease, congenital • nitric oxide

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