Exogenous surfactant attenuation of ischemia-reperfusion injury in the lung through alteration of inflammatory and apoptotic factors.
OBJECTIVE
Lung ischemia-reperfusion injury is associated with impaired gas exchange from increased edema formation and surfactant inactivation. Surfactant replacement therapy is believed to improve gas exchange and lung function, but its effect on inflammation is less well understood. We therefore examined the effects of exogenous surfactant on inflammatory and apoptotic factors in the lung in a rat model of lung ischemia-reperfusion injury.


METHODS
The left lung in rats was subjected to ischemia for 120 minutes and reperfusion for as long as 240 minutes. Sham-treated animals underwent sham surgery and mechanical ventilation for equivalent times. Rats received porcine surfactant or saline solution intratracheally either before or just after ischemia. Lungs were analyzed histopathologically and for expressions of inducible nitric oxide, cytokines, and caspase-3.


RESULTS
Lung ischemia-reperfusion injury resulted in worse lung histopathologic characteristics than in sham-operation animals. At 2 hours of reperfusion, lung ischemia-reperfusion injury animals showed increased pulmonary caspase-3 expression. Moreover, lung ischemia-reperfusion injury resulted in inducible nitric oxide expression at all time points. Exogenous surfactant resulted in less inflammatory cell infiltration and edema in the lungs relative to saline-treated animals. Surfactant decreased activated caspase-3 expression and increased inducible nitric oxide expression relative to saline-treated animals. At 4 hours of reperfusion, surfactant increased interleukin 6 and 10 expressions in the lung.


CONCLUSIONS
This study showed a significant improvement in lung histologic characteristics after surfactant therapy, accompanied by reduced apoptosis and increased anti-inflammatory cytokine levels. Interestingly, surfactant therapy also increased pulmonary inducible nitric oxide expression.
van Putte
Bart P
BP
Department of Intensive Care Medicine, University Medical Center, Utrecht, The Netherlands. bvanputte@yahoo.com
Cobelens
Pieter M
PM
van der Kaaij
Niels
N
Lachmann
Burkhard
B
Kavelaars
Annemieke
A
Heijnen
Cobi J
CJ
Kesecioglu
Jozef
J