Effects of inhaled nitric oxide and surfactant with extracorporeal life support in recovery phase of septic acute lung injury in piglets.
BACKGROUND
To improve survival from septic acute lung injury (ALI), extracorporeal life support (ECLS) is one of the ultimate solutions. We evaluated biochemical and pathological characteristics of recovery phase of septic ALI treated in acute phase by inhaled nitric oxide (NO) and surfactant with ECLS and hypothesized that this combination should exert better lung protective effects than that with conventional mechanical ventilation (CMV).


METHODS
ALI was induced by i.v. endotoxin and 4-6h CMV in young piglets (9-14kg) followed by treatment protocol for 24h in 4 modalities (n=5): VENT, CMV only; VNOS, VENT plus inhaled NO (10ppm) and surfactant (50mg/kg); ECMO, a veno-venous by-pass as extracorporeal membrane oxygenation; ENOS, ECMO plus inhaled NO and surfactant. After treatment they were weaned and maintained for recovery until day 7, and their lungs were processed for assessment of injury and reparation.


RESULTS
Plasma interleukin-8 levels in ENOS were lower than ECMO. On day 7 mRNA expression of inducible NO synthase and nitrite/nitrate levels in BALF were higher in VENT than in ECMO, interleukin-8 mRNA expression and lung apoptosis were lower in ENOS than in ECMO; disaturated phosphatidylcholine and mRNA expression of hepatocyte growth factor were higher, interleukin-8 content, NO synthase mRNA expression and malondialdehyde in lung tissue were lower, and morphologically lung injury and apoptosis were milder, in ENOS than in VENT.


CONCLUSIONS
ECLS combined with inhaled NO and surfactant alleviated septic injury and facilitated reparation in the lung recovery in contrast to CMV or ECMO alone.
Song
Junfeng
J
Laboratory of Pediatric Respiratory and Intensive Care Medicine, Children's Hospital, Fudan University, 399 Wanyuan Road, Shanghai 201102, China.
Palmer
Kenneth
K
Sun
Bo
B
D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods*; D005786:Gene Expression Regulation; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012121:Respiration, Artificial / Q000379:methods; D018805:Sepsis / Q000150:complications; D013552:Swine
D016209:Interleukin-8; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D009569:Nitric Oxide; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II