In this study, inhalation of 40 ppm NO, regardless of the administration of CPAP, lowered the elevated mean Ppatm and PVR. Inhalation of NO at concentrations of 5 to 80 ppm previously has been shown to produce selective pulmonary vasodilation in subjects with pulmonary hypertension secondary to global hypoxemia, primary pulmonary hypertension, and adult respiratory distress syndrome. However, inhalation of NO did not affect mean Psa and SVR in our dogs. This is in agreement with the concept of a selective dilator effect of inhaled NO on the pulmonary vasculature. The absence of systemic vascular effects is explained by high-affinity binding of NO to hemoglobin. Compatible with previous observations, this inactivation of NO did not significantly affect blood levels of methemo-globin.
Our results show that inhaled NO has pulmonary vasodilator effects, even when PVR had already been lowered by restoration of lung volume with CPAP. This finding was expected, because NO inhalation dilates selectively blood vessels in ventilated lung areas. Application of CPAP during acute lung injury has been shown to recruit additional lung units for gas exchange and thereby may dilate additional blood vessels previously not exposed to the NO present in the gas phase. Apparently, changes in lung volume altering the gas exchange surface area are sufficient to optimize the selective pulmonary vasodilator effect of inhaled NO.
Although inhalation of NO in the absence of CPAP caused significant pulmonary vasodilation, pulmonary gas exchange remained essentially unchanged. This contrasts with observations made during administration of intravenous vasodilators that have been reported to relieve regional hypoxic pulmonary vasoconstriction, increase pulmonary blood flow to shunt units, and reduce arterial blood oxygenation. In the absence of CPAP, pulmonary vasodilation during NO inhalation was apparently not sufficient to divert pulmonary blood flow from nonventilated to well-ventilated lung units. Apparently, the lack of well-ventilated lung areas limited the effect of NO inhalation alone on the Va/Q mismatch.