Twenty-five percent albumin prevents lung injury following shock/resuscitation.
OBJECTIVE
To evaluate novel indications for the use of human albumin solutions in the prevention and treatment of acute lung injury following shock/resuscitation and to test the hypothesis that 25% human albumin is an effective resuscitation fluid as well as an immunomodulatory agent protective against lung injury in our model.


METHODS
A previously developed rodent model of acute lung injury in which resuscitated shock primes for increased lung injury in response to a small dose of intratracheal lipopolysaccharide.


METHODS
University-affiliated hospital.


METHODS
Sprague Dawley rats weighing 300-350 g.


METHODS
Animals were bled to a mean arterial pressure of 40 mm Hg and maintained in a shock phase for 1 hr. Animals then were resuscitated by transfusion of the shed blood plus an equal volume of Ringer's lactate or their shed blood plus 3 mL/kg volume of 25% albumin or their shed blood plus 15 mL/kg of 5% human albumin over a period of 2 hrs. To test for the possible role of 25% albumin as an antioxidant, we also performed resuscitation with Ringer's lactate supplemented with N-acetylcysteine or 25% albumin depleted of its antioxidant properties by N-ethylmaleimide. Mean arterial pressure was monitored continuously. One hour after resuscitation, 100 microg of lipopolysaccharide in 200 microL of saline was administered intratracheally.


RESULTS
Resuscitation with 25% albumin significantly reduced transpulmonary protein flux, bronchoalveolar lavage fluid neutrophil counts, and the degree of histopathological injury compared with resuscitation with Ringer's lactate or 5% albumin. To delineate the underlying mechanism of this beneficial effect, the production of cytokine-induced neutrophil chemoattractant as well as nuclear translocation of its critical transcription factor nuclear factor-kappaB was measured. Both cytokine-induced neutrophil chemoattractant messenger RNA concentrations and nuclear factor-kappaB translocation were diminished following 25% albumin resuscitation. Furthermore, 25% albumin significantly decreased lipid peroxidation in plasma as measured by 8-isoprostane concentrations. N-ethylmaleimide modified 25% albumin, possessing lesser antioxidant activity, exhibited an attenuated protection from lung injury.


CONCLUSIONS
Resuscitation with 25% albumin attenuates lung injury in this rat model. The beneficial effect was due to reduced neutrophil sequestration. The antioxidant properties of the 25% albumin preparation appeared to be partially responsible for the effects observed. These studies suggest a novel role for 25% albumin as an anti-inflammatory agent in neutrophil-mediated diseases, such as acute respiratory distress syndrome.
D000418:Albumins / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000401:mortality / Q000517:prevention & control*; D012151:Resuscitation / Q000379:methods*; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000401:mortality / Q000628:therapy*
D000418:Albumins