Effects of hyaluronan-fortified surfactant in ventilated premature piglets with respiratory distress.
We hypothesized that enriching surfactant with hyaluronan would restore lung function when tested in a premature animal model. Newborn piglets (85% gestation, term 112-114 days) were delivered by cesarean section, subjected to mechanical ventilation (tidal volume 6- 8 ml/kg) and randomly assigned to treatment with 50 or 100 mg/kg Curosurf (C50 and C100), 50 or 100 mg/kg Curosurf mixed with 2.5% HA (w/w, CH50 and CH100). A ventilated and not treated group (Cont) and a not treated and not ventilated group (Non) were included as controls. Six hours after treatment the lungs were removed and biochemical, biophysical, cytological and histological analyses were carried out. The CH100, CH50, C100 and C50 groups had variable but significantly improved alveolar phospholipid content, minimal surface tension, alveolar aeration and wet/dry lung weight ratios, but little histological evidence of lung injury. CH100, CH50 and C100 groups had the best effects in terms of oxygenation, lung compliance and histology and evidence of decreased inflammation (IL-8 and TNF-alpha mRNA expression). We conclude that HA added to 50 mg/kg Curosurf or use of 100 mg/kg Curosurf with or without HA provides the best effects in terms of lung function and reduction of inflammation.
Wang
Xiaoning
X
Laboratory of Pediatric Respiratory and Intensive Care Medicine, Children's Hospital of Fudan University, Shanghai, PR China.
Sun
Zhonghou
Z
Qian
Liling
L
Guo
Chunbao
C
Yu
Wenliang
W
Wang
Wei
W
Lu
Karen W
KW
Taeusch
H William
HW
Sun
Bo
B
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001688:Biological Products / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008315:Malondialdehyde / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D010743:Phospholipids / Q000008:administration & dosage*; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000473:pathology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000893:Anti-Inflammatory Agents; D001688:Biological Products; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008315:Malondialdehyde; D006820:Hyaluronic Acid; D009195:Peroxidase; C068291:poractant alfa