Use of Inhaled Nitric Oxide and Acetlcholine in the Evaluation of Pulmonary Hypertension and Endothelial Function After Cardiopulmonary Bypass

Background. Increased pulmonary vascular resistance is common in congenital heart disease and is exacerbated by cardiopulmonary bypass (CPB). We investigated whether CPB is responsible for pulmonary endothelial dysfunction and contributes to postoperative pulmonary hypertension. Methods and Results. We infused the endothelium-dependent vasodilator acetylcholine (ACH) into the pulmonary circulation of pulmonary hypertensive children with congenital heart disease either before (n = 12) or after (n=22) surgical repair on CPB. The dose response to ACH (10- ` to 10-6 M) was recorded for all hemodynamic variables. Nine additional postoperative patients were studied with ACH followed by inhalation of 80 ppm nitric oxide, an endothelium-independent smooth muscle relaxant. Plasma levels of cyclic GMP (cGMP) were measured before and after ACH and nitric oxide administration. Pulmonary vasodilation with 10- ' M ACH was seen in all preoperative patients but was markedly attenuated in postoperative patients. Baseline pulmonary vascular resistance (5.6 ± 1.0 U m2) fell 46±5 % in preoper-ative patients but declined only 11±4 % from baseline (5.8±0.9 U m2) in postoperative patients (P<.002). However, inhalation of 80 ppm nitric oxide after ACH infusion in postoperative patients lowered pulmonary vascular resistance by 33±4 % (P<.0002 compared with postoperative ACH response) with minimal effects on the systemic circulation. This finding suggests that the capacity for smooth muscl