EFFECT OF INHALED NITRIC-OXIDE ON PULMONARY HEMODYNAMICS AFTER ACUTE LUNG INJURY IN DOGS

Increased pulmonary vascular resistance (PVR) and mismatch in ventilat ion-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled d uring hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. We studied the hemodynami c and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atr ial pressure, Ppa, and left ventricular and arterial pressures were me asured, and cardiac output was estimated by an aortic flow probe. Shun t and dead space were also estimated. The effect of 5-min exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hy poxia, and oleic acid-induced ALI. During ALI, partial beta-adrenergic blockade (propranolol, 0.15 mg/kg iv) was induced and 74 ppm NO was i nhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels we re measured. During hyperoxia, NO inhalation had no measurable effects . Hypoxia increased Ppa (from 19.8 +/- 6.1 to 28.3 +/- 8.7 mmHg, P < 0 .01) and calculated PVR (from 437 +/- 139 to 720 +/- 264 dyn.s.cm(-5), P < 0.01), both of which decreased with 17 ppm NO. ALI decreased arte rial PO2 and increased airway pressure, shunt, and dead space ventilat ion. Ppa (19.8 +/- 6.1 vs. 23.4 +/- 7.7 mmHg) and PVR (437 +/- 139 vs. 695 +/- 359 dyn.s.cm(-5), P < 0.05) were greater during ALI than duri ng hyperoxia. NO inhalation had no measurable effect during ALI before or after beta-adrenergic blockade. MetHb of nitroglycerin (15 mu g) i nduced an immediate decrease in Ppa and PVR during ALI. Short-term NO inhalation does not affect PVR or gas exchange in dogs with oleic acid -induced ALI, nor does it increase NO-Hb or MetHb. In contrast, NO can diminish hypoxia-induced elevations in pulmonary vascular tone. These data suggest that NO inhalation selectively dilates the pulmonary cir culation and specifically reduces HPV but not oleic acid-induced incre ases in pulmonary vasomotor tone.