SUSTAINED PULMONARY VASODILATION AFTER INHALED NITRIC-OXIDE FOR HYPOXIC PULMONARY-HYPERTENSION IN SWINE

It has been shown that pulmonary vasodilation is sustained after disco ntinuation of inhaled nitric oxide (INO) during moderate hypoxic pulmo nary hypertension (HPH) in swine. The present investigations demonstra ted how INO dose, hypoxia duration, and endogenous NO production influ ence this important phenomenon. Fifteen adolescent Yorkshire swine wer e randomly assigned to three groups In = 5 each) and underwent the fol lowing phasic experimental protocol: (I) Baseline ventilation (FIO2 = .3); (II) Initiating HPH (FIO2 = .16 to .18, PaO2 = 45 to 55 mm Hg); ( III) INO at 10 ppm; (IV) Posttreatment observation; (V) INO of 80 ppm; and (VI) Posttreatment observation. Phase II (pretreatment hypoxia) l asted 30 minutes in group A (short hypoxia) and 120 minutes in group B (long hypoxia). N-nitro-L-arginine methyl ester (NAME) was used to in hibit nitric oxide synthase (NOS) throughout the experiment in group C (short hypoxia + NAME). Hemodynamics and blood gases were monitored b y systemic and pulmonary artery catheters placed by femoral cutdown. A nalysis of variance with post-hoc adjustment was used to compare group s at each phase, and the paired t test was used for comparisons within a group. With respect to baseline mean pulmonary artery pressure (MPA P) and pulmonary vascular resistance (PVR), there were no significant differences among the three groups. MPAP and PVR were significantly hi gher in group C than in group A during phase II, (MPAP, 76% +/- 8% v 3 3% +/- 2%; PVR, 197% +/- 19% v 78% +/- 10%; P < .05). There were no si gnificant differences in MPAP or PVR during phases III through VI. Whe n MPAP was expressed as percent dilation, 80 ppm caused significantly more dilation than did 10 ppm in all three groups. Groups A and C had significantly higher sustained pulmonary artery dilation after 80 ppm than after 10 ppm (A, 82% +/- 31% v 17% +/- 11%; C, 68% +/- 10% v 42% +/- 12%; both P < .05), but group B did not (43% +/- 15% v 30% +/- 9%; P = .25). High dose results in stronger vasodilation than low dose du ring and after INO for moderate HPH of short duration. Long hypoxia bl unts this high-dose advantage. Endogenous NO inhibition augments HPH b ut does not decrease pulmonary vasodilation during or after INO. Copyr ight (C) 1996 by W.B. Saunders Company