Intra-pulmonary administration of nitric oxide (iNO) or nitric oxide analogs such as nitroprusside produces selective pulmonary vasodilation. However, nitric oxide has been implicated in control of the cerebral as well as the pulmonary circulation. We tested the hypothesis that Neb-NP (a user-friendly analog of iNO) would adversely affect the cerebral circulation while improving pulmonary artery pressure (PAP) during hypoxia-induced pulmonary hypertension in piglets.

Methods: In 19 piglets, blood pressure (BP), PAP, cardiac output(CO) and unilateral cerebral blood flow (CBF) were monitored continuously. After post-operative stabilization, FiO2 was reduced from 0.30 to 0.07. Piglets were monitored for 15 minutes during this hypoxic phase. Next, without altering FiO2, ventilator settings, or nebulizer flow, NP (10 mg/ml, dissolved in 0.9% NaCl, flow 4 lpm) was substituted for 0.9% NaCl in the nebulizer circuit. Neb-NP continued for 15 minutes.

Results: During hypoxia (PaO2 from 160 to 31 torr), PAP rose significantly (15.3 to 29.2 mm Hg; p< 0.001), while BP and CPP did not change significantly. Cardiac output was not significantly affected, while CBF and CBF/CO (the fraction of systemic CO directed toward the brain) rose significantly (21.3 to 40.9 ml/min; 6.4% to 12.6% respectively, both p< 0.001). Consequently, during hypoxia PVR and PVR/SVR increased while CVR and CVR/SVR fell (all p < 0.001). Administration of Neb-NP during hypoxia reduced PAP (29.2 to 20.8 mm Hg; p< 0.001), but not BP (83.5 to 80.2 mm Hg). Neither CO (735 to 709 mL/min), CBF (40.9 to 38.1 mL/min), nor CBF/CO(12.6% to 12.0%) was significantly affected by Neb-NP during hypoxia. Consequently, while PVR and PVR/SVR fell during Neb-NP SVR, CVR, and CVR/SVR did not.

Conclusions: 1) Neb-NP produced prompt, significant, selective reduction of PAP and PVR in piglets with hypoxia-induced pulmonary hypertension. 2) This selective pulmonary vasodilation was produced without apparent effects on either the systemic or cerebral circulations. 3) These observations provide some reassurance regarding possible adverse cerebrovascular consequences of intra-pulmonary administration of nitric oxide analogs.