Severity of hypoxia predicts response to nitric oxide in a porcine pulmonary hypertension model.
Although inhaled nitric oxide (NO) has been variably successful in resolving pulmonary hypertension in neonates, children, and adults, no parameters predictive of response to this therapy have been elucidated. We conducted an animal study to determine if severity of hypoxia can predict magnitude and sustenance of response to inhaled NO therapy. Seven Yorkshire swine weighing 11 to 20 kg underwent 16 experiments, each consisting of four phases: Phase 1: Control period of ventilation on FIO2 .3; phase 2: Hypoxic period on FIO2 .10 to .15, establishing pulmonary hypertension; phase 3: Treatment period with NO starting at five 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 pulmonary hypertension of pre-NO magnitude developed. Each animal underwent a maximum of three experiments in random order of hypoxia severity before sacrifice with pentobarbital overdose. Continuous hemodynamic parameters, intermittent cardiac output and pulmonary capillary wedge pressure, and intermittent arterial blood gas analyses were obtained through pulmonary and systemic artery catheters placed by femoral cutdown. Pulmonary and systemic vascular resistances (PVR and SVR) were calculated by standard formulas. Experiments were divided into two groups (n = 8 in each): group 1 with severe hypoxia (PaO2, 25 to 35) and group 2 with moderate hypoxia (PaO2, 36 to 65). Data for all hemodynamic parameters were expressed as mean percentage change from baseline (phase 1) +/- SEM under each set of conditions, and the two groups were compared by two-way analysis of variance and covariance adjusted for order of experimentation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output; D004195:Disease Models, Animal; D005544:Forecasting; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D011651:Pulmonary Artery; D011660:Pulmonary Heart Disease / Q000517:prevention & control; D011669:Pulmonary Wedge Pressure; D012008:Recurrence; D012121:Respiration, Artificial; D012769:Shock / Q000503:physiopathology; D013552:Swine; D014655:Vascular Resistance
D002245:Carbon Dioxide; D009569:Nitric Oxide; D010100:Oxygen