EFFECTS OF INHALED NITRIC-OXIDE AND NEBULIZED PROSTACYCLIN ON HYPOXICPULMONARY VASOCONSTRICTION IN ANESTHETIZED SHEEP

Objectives: Inhaled nitric oxide has been shown to be a selective pulm onary vasodilator, leading to reduced pulmonary arterial pressure and improved ventilation/perfusion ratio in the acute respiratory distress syndrome, This local pulmonary vasodilation theoretically can be achi eved by the airway application of a short-acting vasodilator, such as prostacyclin. We hypothesized that nebulized prostacyclin has the same properties for selective pulmonary vasodilation as inhaled nitric oxi de, Design: Prospective, experimental study in sheep, Setting: Investi gational intensive care unit in a university hospital, Subjects: Six a dult ewes of the Merino breed, Interventions: Sheep (n = 6) were surgi cally prepared for chronic study, After 5 days of recovery, the sheep had tracheostomies performed under anesthesia. Intubation with a modif ied Robert-Shaw tube allowed side-separated ventilation. The entire le ft lung was ventilated with pure nitrogen, whereas the right lung was ventilated with pure oxygen, Nitric oxide and prostacyclin were added in different concentrations to the nitrogen, with which the left lung was ventilated, Measurements and Main Results: The blood flows to the left and right lungs were measured with ultrasonic flow probes on the common and left pulmonary artery, Measurements were taken after each c ompound had been administered for 10 mins at a predefined dose. Both i nhaled nitric oxide and nebulized prostacyclin caused effective, selec tive, dose-dependent pulmonary vasodilation, Inhaled nitric oxide was able to abolish hypoxic pulmonary vasoconstriction when insufflated in to the animals at a concentration of 50 ppm of nitrogen, but 100 ppm o f nitric oxide had no further effect, Prostacyclin, at a dosage of 10 mu g/min, showed maximum pulmonary vasodilation, which could not be fu rther increased by doubling the dosage, However, prostacyclin produced less dilation than high doses of nitric oxide, and its maximum pulmon ary vasodilation was comparable with that effect obtained under ventil ation with 20 ppm of nitric oxide, Conclusions: Both drugs selectively dilated the pulmonary vasculature in ventilated alveoli, Prostacyclin nebulization is an excellent tool to reduce pulmonary hypertension an d to improve the ventilation/perfusion ratio. Prostacyclin nebulizatio n can be used without the highly sophisticated technical equipment tha t is needed for controlled nitric oxide inhalation, and may therefore become a new, noninvasive therapeutic approach for treatment of adult respiratory distress syndrome in hospitals that cannot provide nitric oxide inhalation.