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Inhaled nitric oxide results in deteriorating hemodynamics when administered during cardiopulmonary bypass in neonatal swine*

Objective To evaluate if inhaled nitric oxide (iNO) has a lung-protective effect when it is delivered during the ischemic phase of neonatal cardiopulmonary bypass (CPB). Design Prospective, randomized, controlled study. Setting Surgical research laboratory in a university hospital. Subjects Thirty-five neonatal swine. Interventions One-week-old swine (2.1–3.4 kg) were exposed to cool, low-flow CPB bypass designed to mimic the bypass used during neonatal congenital heart repair. Animals were randomized to four groups: a) CPB without exposure to iNO (n = 9); b) iNO delivery only during CPB with discontinuation of iNO at the start of reperfusion (n = 7); c) iNO delivery both during CPB and during the 90-min post-CPB observation period (n = 7); and d) iNO delivery only after separation from CPB (n = 7). Each animal was placed on nonpulsatile CPB and cooled to a nasopharyngeal temperature of 18°C (64°F). Low-flow CPB (35 mL·kg−1·min−1) was instituted for 90 mins. The blood flow then was returned to 100 mL·kg−1·min−1, and the animals were warmed to 36°C (96.8°F) before separation from CPB. Animals were followed 90 mins post-CPB. Lung tissue was harvested and evaluated for myeloperoxidase activity, wet/dry weight, and lung pathology. Five animals underwent sham protocol, receiving instrumentation but not exposure to CPB or iNO. Measurements and Main Results We measured pulmonary vascular resistance, right ventricular output, and pulmonary artery pressure in all animals at 30, 60, and 90 mins following separation from CPB. Study animals that received iNO during the ischemic period of CPB were not protected against CPB-induced lung injury. Those animals treated with iNO both during and after CPB trended worse than those receiving iNO only after CPB. Inhaled nitric oxide delivered only after separation from CPB improved the hemodynamic variables compared with all other groups. Differences in lung wet/dry weight, myeloperoxidase, and pathology were not significantly different among groups. Conclusions The delivery of iNO during the ischemic period of CPB does not protect against CPB-induced lung injury in a neonatal piglet CPB model. Delivery of iNO during this phase of CPB may, in fact, worsen the post-CPB hemodynamic condition. Inhaled nitric oxide should be used with caution during periods of low pulmonary blood flow CPB. Inhaled nitric oxide remains effective for reducing pulmonary vascular resistance after CPB.