L-arginine and substance P reverse the pulmonary endothelial dysfunction caused by congenital heart surgery

Background-The increase in pulmonary vascular resistance (PVR) seen in chil dren after cardiopulmonary bypass has been attributed to transient pulmonar y endothelial dysfunction (PED), We therefore examined FED in children with congenital heart disease by assessing the L-arginine-nitric oxide (NO) pat hway in terms of substrate supplementation (L-arginine [L-Arg]), stimulatio n 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 hy pertension undergoing cardiac catheterization who had not had surgery and 1 0 patients (aged 0.65+/-0.73 years) who had recently undergone cardiopulmon ary bypass were examined, All were sedated and paralyzed and received posit ive-pressure ventilation. Blood samples and pressure measurements were take n from catheters in the pulmonary artery and the pulmonary vein or left atr ium, Respiratory mass spectrometry was used to measure oxygen uptake, and c ardiac 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). rn preoperative patients, the lack of an additional significant change of PVR with L-Arg, Sub-P, and inhaled NO suggests little preexisting FED. Postoperative PVR was higher, with an additional pulmonary endothelia l contribution that was restorable with L-Arg and Sub-P. Conclusions-Postoperatively, the rise in PVR suggested FED, which was resto rable by L-Arg and Sub-P, with no additional effect of inhaled NO. These re sults may indicate important new treatment strategies for these patients.