Effect of mechanical ventilation on the pulmonary expression and production of elastin in nitrofen-induced diaphragmatic hernia in rats.
OBJECTIVE
Hypolastic lung in congenital diaphragmatic hernia (CDH) shows markedly thickened alveolar walls, increased interstitial tissue, and markedly diminished alveolar air space, showing morphologic immaturity. Decrease in lung compliance and distensibility often is seen in human CDH as well as experimentally produced CDH. Collagen and elastin, critical components of the lung connective tissue, have been suggested to have important influence on lung compliance and maximal expansion. The barotrauma caused by mechanical ventilation is known to produce structural changes in the pulmonary architecture. The aim of this study was to investigate the expression and production of elastin in the lung in newborn rats with CDH during mechanical ventilation.


METHODS
CDH was induced in rat embryos after administration of nitrofen to pregnant dams on day 9.5 of gestation. Cesarean section was performed on day 21 of gestation. The newborn rats were intubated using a 24-gauge Teflon catheter. After ligation of the umbilical cord, the intubated animals were transferred immediately to a warm plate and connected to a modified ventilator. Ventilation was continued for a maximum of 6 hours. The relative amount of soluble elastin in the lung was assessed using an enzyme-linked immunosorbent assay (ELISA) technique. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of tropoelastin mRNA expression in the lung.


RESULTS
Elastin mRNA in the CDH lung was increased significantly (P <.01) at one hour after ventilation compared with ventilated controls. Elastin protein significantly increased in the CDH lung at one hour (P <.01) and 6 hours (P <.01) after starting ventilation compared with controls.


CONCLUSIONS
The data show that during mechanical ventilation, elastin production is increased significantly in the CDH lung, and this may further affect lung compliance.
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Nino
N
Guarino
Honami
H
Teramoto
Hideki
H
Shima
Takaharu
T
Oue
Prem
P
Puri
D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000209:etiology; D046508:Culture Techniques; D004549:Elastin / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000002:abnormalities / Q000378:metabolism*; D008170:Lung Compliance; D010647:Phenyl Ethers; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014333:Tropoelastin / Q000235:genetics
D010647:Phenyl Ethers; D014333:Tropoelastin; D004549:Elastin; C007350:nitrofen