Combination therapy that targets secondary pulmonary changes after abdominal trauma.
Shock
; 15(6): 479-84, 2001 Jun.
Article
em En
| MEDLINE
| ID: mdl-11386622
ABSTRACT
After abdominal trauma, the lung is susceptible to secondary injury caused by acute neutrophil (PMN) sequestration and alveolar capillary membrane disruption. Adenosine is an endogenous anti-inflammatory metabolite that decreases PMN activation. AICAR ([5-amino-1-[beta-D-ribofuranosyl]imidazole-4-carboxamide]riboside) is the prototype of a novel class of anti-inflammatory drugs that increase endogenous adenosine. After trauma, AICAR administration has been shown to decrease secondary lung injury in models of hemorrhagic shock with delayed lipopolysaccharide challenge and pulmonary contusion. However, early suppression of PMN activation could worsen outcomes after penetrating abdominal trauma. We hypothesized that, after penetrating abdominal trauma, the ideal resuscitation strategy would involve early, short-lived suppression of PMN activation to minimize secondary lung injury, followed by later enhancement of PMN chemotaxis and phagocytosis [using granulocyte colony-stimulating factor (G-CSF)] to lessen late septic complications. G-CSF has not been shown to potentiate PMN mediated pulmonary reperfusion injury. Swine were subjected to cecal ligation/incision and hemorrhagic shock (trauma), followed by resuscitation with shed blood, crystalloid, and either G-CSF, a combination of G-CSF and AICAR, or 0.9% normal saline. At 72 h, bronchoalveolar lavage (BAL) leukocyte counts and protein concentration were determined, and lung tissue analysed for myeloperoxidase (MPO, a measure of PMN infiltration) and microscopic pathology. Analysis of BALs revealed a significant increase protein concentrations and in white blood cell and PMN infiltration (P< 0.05) following trauma. These acute changes were not exacerbated by G-CSF, but were reversed by combined AICAR + G-CSF, which implicates a physiologic role for adenosine. This suggests that combination therapy may have beneficial effects on the lung after trauma.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleotídeos
/
Choque Hemorrágico
/
Abscesso Abdominal
/
Lesão Pulmonar
/
Aminoimidazol Carboxamida
/
Hemodinâmica
/
Traumatismos Abdominais
/
Pulmão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Shock
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos