SEVERITY OF HYPOXIA PREDICTS RESPONSE TO NITRIC-OXIDE IN A PORCINE PULMONARY-HYPERTENSION MODEL

Although inhaled nitric oxide (NO) has been variably successful in res olving pulmonary hypertension in neonates, children, and adults, no pa rameters predictive of response to this therapy have been elucidated. We conducted an animal study to determine if severity of hypoxia can p redict magnitude and sustenance of response to inhaled NO therapy. Sev en Yorkshire swine weighing 11 to 20 kg underwent 16 experiments, each consisting of four phases: Phase 1: Control period of ventilation on FlO(2).3; phase 2: Hypoxic period on FlO(2).10 to.15, establishing pul monary hypertension; phase 3: Treatment period with NO starting at fiv e parts per million (ppm), doubling dose every 10 min to 80 ppm; phase 4: Posttreatment observation period after discontinuation of NO while maintaining hypoxia for 1 hour or until circulatory failure or pulmon ary hypertension of pre-NO magnitude developed. Each animal underwent a maximum of three experiments in random order of hypoxia severity bef ore sacrifice with pentobarbital overdose. Continuous hemodynamic para meters, intermittent cardiac output and pulmonary capillary wedge pres sure, and intermittent arterial blood gas analyses were obtained throu gh pulmonary and systemic artery catheters placed by femoral cutdown. Pulmonary and systemic vascular resistances (PVR and SVR) were calcula ted by standard formulas. Experiments were divided into two groups (n = 8 in each): group 1 with severe hypoxia (Pao(2), 25 to 35) and group 2 with moderate hypoxia (Pao(2), 36 to 65). Data for all hemodynamic parameters were expressed as mean percentage change from baseline (pha se 1) +/- SEM under each set of conditions, and the two groups were co mpared by two-way analysis of variance and covariance adjusted for ord er of experimentation. The severely hypoxic group showed significantly less improvement than the moderately hypoxic group in mean pulmonary artery pressure during treatment with NO (17 +/- 3% versus -2 +/- 3%, P = .005) and after discontinuing the drug (55 +/- 11% versus 21 +/- 7 %, P = .03). The severely hypoxic group also experienced a significant elevation in cardiac output during NO therapy when compared with the moderately hypoxic group (26 +/- 6% versus 3 +/- 4%, P = .02). Further more, there were no incidents of circulatory failure after discontinui ng NO during moderate hypoxia versus three incidents (38%) during seve re hypoxia, all of which were immediately reversed by restarting NO. I n a porcine hypoxic pulmonary hypertension model, severe hypoxia predi cts weaker improvement in the pulmonary hypertension during NO therapy and stronger recurrence after discontinuing the drug. Nitric oxide ma y also have a hemodynamic supportive role during severe hypoxia by enh ancing cardiac output and preventing acute cor pulmonale. Copyright (C ) 1995 by W.S. Saunders Company.