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Volume 3 Supplement 2

International Symposium on the Pathophysiology of Cardiopulmonary Bypass

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


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 nitric oxide release (substance P [Sub-P]), and end-product provision (inhaled NO) before and after open heart surgery.


Ten unoperated patients (0.62 ± 0.27 years) with pulmonary hypertension undergoing cardiac catheterisation, and 10 patients (0.64 ± 0.73 years) early after cardiopulmonary bypass were examined. All were sedated, paralysed 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 = 0.65, and then during additional intravenous infusion of L-Arg (15 mg/kg/min), Sub-P (1 pmol/kg/min), and finally inhalation of NO (20 parts per million).


In both patient groups, oxygen supplementation was the most potent pulmonary vasodilator. In preoperative patients, the lack of a further significant change with L-Arg, Sub-P and inhaled NO suggests little pre-existing PED. Postoperative PVR was higher with an additional endothelial contribution that was restorable with L-Arg and Sub-P. (see Figure)

figure 1


Postoperatively, the rise in PVR suggested pulmonary endothelial dysfunction 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.

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Schulze-Neick, I., Penny, D., Rigby, M. et al. L-arginine and substance P reverse the pulmonary endothelial dysfunction caused by congenital heart surgery. Crit Care 3 (Suppl 2), P14 (1999).

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