Intratracheal administration of sildenafil and surfactant alleviates the pulmonary hypertension in newborn piglets.
OBJECTIVE
To study systemic and pulmonary effects of low-dose sildenafil with surfactant in newborn piglets with pulmonary hypertension (PHT) induced by thromboxane A(2) analog (U46619).


METHODS
Piglets (1-3 days, 1.7-2.5 kg) were mechanically ventilated and prepared for the continuous measurement of mean systemic and pulmonary arterial pressures (MAP and PAP, respectively), heart rate and pulmonary artery flow (as cardiac output). Following stabilization, PHT was induced by intravenous U46619 infusion (0.2-0.8 microg/kg/min) for 120 min. Piglets were randomized for intratracheal administration of surfactant (BLES, 4 ml/kg) with saline (n=6) or sildenafil (0.05 mg/kg, n=6) given after 60 min of U46619 treatment. Temporal changes of hemodynamic measurements were analyzed by two-way ANOVA.


RESULTS
There was progressive PHT induced by U46619 (161% of baseline), with increased PAP and pulmonary vascular resistance and decreased cardiac output. Surfactant and sildenafil combined improved PAP along with reduced pulmonary vascular resistance. Cardiac output was higher with surfactant and sildenafil combined than surfactant alone. No significant changes in heart rate, stroke volume, MAP and systemic vascular resistance were observed. Ratio of PAP:MAP was lowered with surfactant and sildenafil combined. Systemic oxygen consumption was not different between groups but the oxygen extraction ratio was higher than baseline in surfactant alone (P<0.05).


CONCLUSIONS
Adding low-dose sildenafil to surfactant is effective in alleviating the progressive PHT developed in newborn piglets induced by thromboxane A(2). Intratracheal sildenafil may be a useful therapeutic adjunct to critically ill neonates with PHT.
Obaid
Laila
L
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Johnson
Scott T
ST
Bigam
David L
DL
Cheung
Po-Yin
PY
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects*; D004359:Drug Therapy, Combination; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D007442:Intubation, Intratracheal; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000009:adverse effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D013501:Surface-Active Agents; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000068677:Sildenafil Citrate