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Twenty-five percent albumin prevents lung injury following shock/resuscitation. |
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Twenty-five
percent albumin prevents lung injury following
shock/resuscitation.
Powers KA, Kapus A, Khadaroo RG, He R, Marshall JC, Lindsay TF, Rotstein OD.
Crit
Care Med 2003 Sep;31(9):2355-63.
SUMMARY: 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.DESIGN 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.SETTING University-affiliated hospital.SUBJECTS Sprague Dawley
rats weighing 300-350 g.INTERVENTIONS 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.MEASUREMENTS AND MAIN 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.
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