Inhaled nitric oxide versus prostacyclin in chronic shunt-induced pulmonary hypertension.
OBJECTIVE
Cardiac surgery for congenital heart defects is commonly complicated by shunt-induced chronic pulmonary hypertension and associated acute hypertensive crises. To investigate the effects of vasodilators in chronic and acute pulmonary hypertension, we used the innominate artery to create a growing aortopulmonary shunt in young piglets.


METHODS
Pulmonary hemodynamics and right ventricular function and their responses to hypoxia, intravenous prostacyclin, and inhaled nitric oxide were investigated after closure of the shunt by using pulmonary flow-pressure relationships, pulmonary vascular resistance partitioning, pulmonary vascular impedance, and ventriculoarterial coupling expressed as the ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance.


RESULTS
Shunt-induced pulmonary hypertension was associated with medial hypertrophy of pulmonary arteries, increased resistance, increased elastance, increased wave reflection, and preserved ventriculoarterial coupling. Hypoxic pulmonary vasoconstriction was blunted in the shunt group. Compared with prostacyclin, inhaled nitric oxide was a more effective vasodilator in the shunt group and in hypoxia. Effective pulmonary arterial elastance and right ventricular end-systolic elastance increased in chronic (shunt) and acute (hypoxic) hypertension and decreased with vasodilators, preserving a normal coupling.


CONCLUSIONS
A growing aortopulmonary shunt in the young pig is a reliable model of chronic pulmonary hypertension, with medial hypertrophy, increased resistance, and increased elastance. In this model inhaled nitric oxide is a better pulmonary vasodilator than intravenous prostacyclin, with neither drug having a specific inotropic effect, and normal coupling is preserved in chronic and acute pulmonary hypertension.
Wauthy
Pierre
P
Laboratory of Physiology, Free University of Brussels, Belgium. pierre.wauthy@wanadoo.be
Abdel Kafi
Sophia
S
Mooi
Wolter J
WJ
Naeije
Robert
R
Brimioulle
Serge
S
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D011464:Epoprostenol / Q000008:administration & dosage*; D005260:Female; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000860:Hypoxia / Q000188:drug therapy; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D011336:Probability; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D012680:Sensitivity and Specificity; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D011464:Epoprostenol