Inhaled nitric oxide (iNO) has been shown to selectively reduce pulmonary hypertension in several biologic models. However, iNO is not as convenient as one might wish. We tested the effects of Neb-NP (a user-friendly analog of inhaled nitric oxide) on pulmonary and systemic hemodynamics during pulmonary hypertension induced by hypoxia in piglets.

Methods: In 19 piglets, we determined the time course of the acute (minutes) and longer-term (one hour) systemic and pulmonary hemodynamic effects of Neb-NP during hypoxia-induced pulmonary hypertension, and the rebound when Neb-NP was discontinued but hypoxia persisted. We assessed the effects of pre-treatment with Dip, a phosphodiesterase inhibitor proposed to enhance the effects of Neb-NP. Finally, we compared Neb-NP to another commonly used vasodilator, tolazoline (Neb-Tz).

Results: During hypoxia-induced pulmonary hypertension, Neb-NP caused pulmonary artery pressure (PAP) to fall significantly (29.2 to 20.8 mm Hg; p< 0.001), but neither BP (83.5 to 80.2 mm Hg) nor CO (735 to 709 mL/min) changed significantly. Consequently, PVR and PVR/SVR fell significantly (both p<.001) while SVR was unaffected. Selective pulmonary vasodilation began within two minutes of the onset of Neb-NP, and did not wane over one hour. In contrast, after Neb-NP was discontinued, PAP and PVR rose within five minutes (both p<.01). The rebound of pulmonary hypertension after Neb-NP was discontinued was significantly reduced in piglets pre-treated with Dip. In contrast to Neb-NP, Neb-Tz did not reduce PAP during hypoxia(-1.1 ± 1.4 mm Hg) but did produce a significant reduction in BP (-7.7± 6.5 mmHg; p<0.05).

Conclusions: 1) Neb-NP produced prompt, significant, selective reduction of PAP, PVR, and PVR/SVR in piglets with hypoxia-induced pulmonary hypertension. 2) Selective pulmonary vasodilation appeared within minutes of the onset of Neb-NP and persisted for up to one hour, without tachyphylaxis. 3) Neb-NP may provide a user-friendly means to produce selectively pulmonary vasodilation in ventilated or non-ventilated patients with pulmonary hypertension.