EFFECTS OF INHALED NITRIC-OXIDE AND EXTRACORPOREAL MEMBRANE-OXYGENATION ON PULMONARY HEMODYNAMICS AND LYMPH-FLOW IN OLEIC-ACID LUNG INJURY IN SHEEP

Objective: To compare the effects of inhaled nitric oxide (NO) and ext racorporeal membrane oxygenation (ECMO) on oxygenation, hemodynamics, and lymphatic drainage in an oleic acid lung injury model in sheep. De sign: Prospective, randomized study. Setting: Animal research laborato ry. Animals: Thirty female sheep, weighing 35 to 40 kg. Interventions: Acute lung injury was induced by central venous injection of oleic ac id (0.5 mL/kg body weight). A chronic lymph fistula had been prepared through a right thoracotomy 3 days before the experiment. Animals were assigned randomly to the NO group (n = 14) or the ECMO group (n = 16) . When a lung injury score of >2.5 was achieved, the animals were give n NO in dosage increments of 2, 5, 10, 20, and 40 parts per million (p pm), or placed on ECMO with an Fio(2) of 0.21 (ECMO-21) and then 1.0 ( ECMO-100) at the oxygenator. Mechanical ventilator parameters were kep t constant to isolate the effects of NO and ECMO on systemic and pulmo nary hemodynamics, cardiac output, oxygenation parameters, lymph/plasm a protein ratio, and lymph flow. Measurements and calculations were pe rformed after 1 hr at each individual step of NO concentration or Fio( 2). Measurements and Main Results: In the ECMO group, PVRI and MPAP di d not change and were significantly different from the NO group. In th e NO group, there was a dose-dependent decrease in venous admixture, m aximal at 10 ppm NO and decreasing from 40 +/- 6% to 23 +/- 10% (p<.05 ). This decrease was significantly different from the ECMO group, wher e there was no change. There was a significant increase in Pao(2)/Fio( 2) in the NO group, maximal at 10 ppm NO (84 +/- 11 to 210 +/- 90, p<. 05), but a greater increase in Pao(2)/ Fio(2) on ECMO-21 (81 +/- 14 to 265 +/- 63) and a further increase on ECMO-100 (398 +/- 100) (p <.05) . The lymph/plasma protein ratio remained unchanged in both groups aft er induction of lung injury by oleic acid. However, lymph flow decreas ed by 11 +/- 6% in the NO group, whereas it increased by 14 +/- 17% in the ECMO group (p < .05). Conclusions: In an oleic acid-induced sheep model of acute lung injury, there were significant differences betwee n the effects of NO and ECMO on acute pulmonary hypertension, hypoxemi a, hypercarbia, and lymph flow. NO significantly decreases pulmonary h ypertension, whereas pulmonary hemodynamics were not substantially aff ected by ECMO. Both interventions reversed hypoxemia, but ECMO did so to a greater degree, and only ECMO improved hypercarbia. Only NO decre ased lymph flow, possibly as an effect of decreased microvascular filt ration pressure. This study did not attempt to evaluate the impact of these interventions on ventilatory requirements, barotrauma, or outcom e. However, this model suggests that NO therapy may moderate pulmonary hypertension and improve lymph flow in acute lung injury. Clinical st udies are needed to assess whether NO therapy might be beneficial in t reatment of severe acute lung injury in older children and adults.