Inhaled nitric oxide affects endogenous surfactant in experimental lung transplantation.
BACKGROUND
Inhalation of nitric oxide (NO) has been proposed as a therapy to improve lung transplantation outcome. We investigated the effect that inhaled NO has on the surfactant system in the context of ischemia-reperfusion injury.


METHODS
Single left-lung transplantation was performed in weight-matched pairs of Landrace pigs. A double-lung block from the donor animal was flushed with University of Wisconsin solution at 4 degrees C followed by immersion in cold University of Wisconsin solution for 22 hr. The left donor lung was transplanted into the recipient. Recipients were divided into two groups: (1) treated with inhaled NO (40 ppm) (n=6) immediately after initiating lung reperfusion and (2) without treatment (n=6). Lung function was measured during 2 hr of reperfusion. Surfactant components in small and large aggregates, isolated from cell-free bronchoalveolar lavages, and surfactant function were measured.


RESULTS
NO inhalation significantly decreased arterial oxygenation. With respect to the surfactant system, NO inhalation worsened the surfactant adsorption rate to an air-liquid interface and affected levels of hydrophobic surfactant proteins (SPs), SP-B and SP-C, and phospholipids, which decreased in large surfactant aggregates but not in small surfactant aggregates. SP-A was reduced in large surfactant aggregates of transplanted lungs from both untreated and NO-treated groups.


CONCLUSIONS
A decreased level of SP-A, SP-B, and SP-C in large surfactant aggregates of transplanted lungs treated with NO is a marker of lung injury. We conclude that treatment with inhaled NO after lung transplantation is deleterious for the surfactant system and causes a parallel worsening of arterial oxygenation.
Valiño
Fernando
F
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
Casals
Cristina
C
Guerrero
Rosa
R
Alvarez
Lourdes
L
Santos
Martín
M
Sáenz
Alejandra
A
Varela
Andrés
A
Claro
Miguel A
MA
Tendillo
Francisco
F
Castillo-Olivares
José L
JL
D000241:Adenosine; D000280:Administration, Inhalation; D000493:Allopurinol; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005978:Glutathione; D007328:Insulin; D008168:Lung; D016040:Lung Transplantation / Q000502:physiology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D010100:Oxygen / Q000097:blood; D011663:Pulmonary Surfactants / Q000302:isolation & purification*; D011887:Raffinose; D012129:Respiratory Function Tests; D013552:Swine; D014184:Transplantation, Homologous
D007328:Insulin; D019188:Organ Preservation Solutions; D011663:Pulmonary Surfactants; C055206:University of Wisconsin-lactobionate solution; D009569:Nitric Oxide; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D010100:Oxygen