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Published ahead of print on January 7, 2004, doi:10.1164/rccm.200310-1417OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 6, March 2004, 739-748

A more recent version of this article appeared on March 15, 2004
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Submitted on October 16, 2003
Accepted on January 4, 2004

High Tidal Volume Ventilation Causes Different Inflammatory Responses in Newborn versus Adult Lung

Martin Post1*, Ian B Copland2, Francisco Martinez3, Brian P Kavanagh4, Jaques Belik5, Doreen Engelberts6, and Colin McKerlie2

1 Lung Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Pediatrics, University of Toronto, Toronto, Ontario, Canada, 2 Lung Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, 3 Pediatrics, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil, 4 Lung Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; Critical Care Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada, 5 Lung Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; Pediatrics, University of Toronto, Toronto, Ontario, Canada, 6 Lung Biology, The Hospital for Sick Children, Toronto, Ontario, Canada

* To whom correspondence should be addressed. E-mail: martin.post{at}sickkids.ca.

We investigated the effect of high tidal volume (HV) ventilation on adult and newborn rats, by examining pulmonary injury and cytokine mRNA. Based on compliance, edema formation and histology, ventilation with 25 mL kg-1 was more injurious to adult rats than newborns. Ventilation with 40 mL kg-1 minimally affected compliance in newborns, but caused death in adults. Ventilation of adults for 30 minutes at 25 mL kg-1 up-regulated the mRNA expression of IL-1{beta}, IL-6, TNF-{alpha}, MIP-2 and IL-10, while in newborns such ventilation only increased mRNA expression of MIP-2 and IL-10. When tidal volume was raised to 40 mL kg-1 in newborns, IL-1{beta} mRNA levels were additionally increased at 30 minutes, while ventilation for 3 hours additionally increased IL-6 and TNF-{alpha} mRNA. In newborns, the addition of 100% O2 to 30 minutes ventilation blunted the HV induction of IL-1{beta}, IL-10 and MIP-2 mRNA expression, while at 3 hours, 100% O2 concentration synergistically increased the mRNAs for TNF-{alpha} and IL-6. Overall, adult rats are more susceptible to HV-induced lung injury compared to newborns. In newborns the inflammatory response is dependent on tidal volume, duration and supplemental O2. Thus, recommendations for tidal volume limitation based on adult data may be inappropriate for newborns.
Key words: tidal volume, oxygen, cytokines,lung maturity




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