Contribution of pulmonary surfactant with inhaled nitric oxide for treatment of pulmonary hypertension.
BACKGROUND
Combined therapy of inhaled nitric oxide (iNO) with pulmonary surfactant replacement was reported to improve oxygenation in patients or animal models of persistent pulmonary hypertension of the newborn with pulmonary surfactant deficiency lung. To evaluate the potential of iNO for the treatment of persistent pulmonary hypertension of the newborn, pulmonary arterial pressure (PAP) was measured during iNO before and after pulmonary surfactant replacement in an animal model of pulmonary hypertension with surfactant deficiency.


METHODS
Seven newborn piglets were injected with L-nitro-arginine-methylester to produce an animal model of pulmonary hypertension. After PAP increased, iNO (30 p.p.m.) was introduced. Then iNO was stopped, and animals were subjected to lung lavage with saline. After recording the effect of iNO, all animals then received exogenous pulmonary surfactant installation. After surfactant treatment, iNO was again introduced.


RESULTS
Pulmonary arterial pressure and systemic arterial pressure were increased significantly by >30% after infusion of L-nitro-arginine-methylester. During iNO only PAP was reduced significantly. Respiratory system compliance decreased significantly after lung lavage, and increased significantly after pulmonary surfactant replacement with concomitant increase of PaO2. In contrast, significant reduction of PAP with iNO before and after pulmonary surfactant replacement were also observed. The reduction ratios of PAP under each condition were 75.2 +/- 7.4%, 81.3 +/- 3.1%, and 79.1 +/- 5.3%, respectively (not significant among conditions).


CONCLUSIONS
These results suggest that iNO is still a potent pulmonary arterial vasodilator even under pulmonary surfactant deficiency in an animal model of pulmonary hypertension.
Kusuda
Satoshi
S
Department of Neonatology, Osaka City General Hospital, Japan.
Kim
Tae-Jang
TJ
Koriyama
Takeshi
T
Matsunami
Satoko
S
Nakanishi
Hidehiko
H
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D004359:Drug Therapy, Combination; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D013552:Swine; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D011663:Pulmonary Surfactants; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester