Administration of Exogenous NO

Hypoxic pulmonary vasoconstruction (HPV) can be reversed by adding NO to hypoxic gas, as demonstrated by administering 40 to 80 ppm NO during acute hypoxia with an inspired O2 fraction (FIqj) of 0.06 (6%) in an awake sheep with a tracheostomy (Frostell et al., 1991). Pison et al. 

During endogenous release of thromboxane hi, after provoking the heparin-protamine reaction in awake sheep, Fratacci et a/. (1991) confirmed that inhaled NO can act as a selective pulmonary vasodilator. Significant reduction of the peak pulmonary artery pressure (PAP) required an inhaled NO dose of 180 ppm in this study. Furthermore, after indomethacin blockade of arachidonic acid metabolite production, it was shown that inhaled NO still dilated the lung vasculature (Fratacci etal., 1991). Thus, the vasodilatory effect of NO in sheep is independent of prostacyclin release. 

Malmros et al. (1995) studied anesthetized sheep during sham dialysis, which is known to activate circulating leukocytes and platelets, making them sticky and sequester them in the pulmonary vasculature. Comparing controls with animals breathing 50 ppm NO for 1 hr, they showed that inhaled NO reduced the reversible pulmonary sequestration of leukocytes and platelets. 

Very few animal studies have addressed the question of whether addition of NO to inhaled gas has benefits in addition to improved gas exchange and/or central hemodynamics. Zayek et al. (1993) randomized newborn near-term lambs with experimentally induced persistent pulmonary hypertension by ductus ligation. They compared the effect of prolonged inhalation of 80 ppm NO to that of a control group, with both groups mechanically ventilated postnatally for 23 hr. A significant increase in the survival of lambs by inhaling NO was reported. 

It was hypothesized that airway tone may be affected by inhalation of NO. Dupuy et al. (1992) reported a reduction in bronchoconstriction with NO, studying open chest guinea pigs in a body plethysmograph during provocation with intravenous methacholine. A dose-dependent relaxation between 5 and 300 ppm NO was noted, with normalization of the reduced compliance at inhaled doses above 100 ppm NO. In the same model provocation with histamine, leukotriene D4, and neurokinin A was studied. Inhaled NO reverses bronchoconstriction induced by all of these inflammatory mediators (Dupuy et al., 1993a). Work with methylene blue and NO inhalation 

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