Lung injury after hemorrhage is age dependent: role of peroxisome proliferator-activated receptor gamma.
OBJECTIVE
The incidence of multiple organ failure in pediatric trauma victims is lower than in the adult population. However, the molecular mechanisms are not yet defined. We investigated whether the pathophysiologic characteristics of hemorrhage-induced lung injury may be age dependent and may be regulated by the peroxisome proliferator-activated receptor gamma (PPARgamma).


METHODS
Prospective, laboratory investigation that used an established rodent model of hemorrhagic shock.


METHODS
University hospital laboratory.


METHODS
Young (n = 67; 3-5 months old) and mature (n = 66; 11-13 months old) male rats.


METHODS
Hemorrhagic shock was induced in young and mature rats by withdrawing blood to a mean arterial blood pressure of 50 mm Hg. After 3 hours, rats were rapidly resuscitated by infusing the shed blood and killed 3 hours thereafter.


RESULTS
In young rats, lung injury was characterized by accumulation of red cells and neutrophils at the end of the resuscitation period; on Western blot analysis, lung expression of intercellular adhesion molecule-1 was increased. In contrast, the severity of lung injury was more pronounced in mature rats. Lung myeloperoxidase activity and expression of constitutive and inducible intercellular adhesion molecule-1 was significantly higher in mature rats compared with young rats. Mature rats also had higher plasma levels of cytokines and chemokines compared with young rats. This heightened inflammation was associated with higher degree of activation of nuclear factor-kappaB and down-regulation of PPARgamma and heat shock factor-1 in the lung of mature rats compared with young rats. Treatment with the PPARgamma ligand, the cyclopentenone prostaglandin 15-deoxy-Delta-prostaglandin J2, ameliorated lung injury in young, but not in mature animals.


CONCLUSIONS
Lung injury after severe hemorrhage is age dependent and may be secondary to a diverse regulation of PPARgamma.
Zingarelli
Basilia
B
Department of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. basilia.zingarelli@cchmc.org
Hake
Paul W
PW
O'Connor
Michael
M
Burroughs
Timothy J
TJ
Wong
Hector R
HR
Solomkin
Joseph S
JS
Lentsch
Alex B
AB
D055371:Acute Lung Injury / Q000209:etiology*; D000367:Age Factors; D000818:Animals; D008297:Male; D047495:PPAR gamma / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000503:physiopathology
D047495:PPAR gamma