S. Emil et al., SEVERITY OF HYPOXIA PREDICTS RESPONSE TO NITRIC-OXIDE IN A PORCINE PULMONARY-HYPERTENSION MODEL, Journal of pediatric surgery, 30(7), 1995, pp. 930-936
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.