Combination therapy that targets secondary pulmonary changes after abdominal trauma

Kimberly A. Davis, Timothy C. Fabian, D. Nicholas Ragsdale, Lisa L. Trenthem, Martin Croce, Kenneth G. Proctor

Research output: Contribution to journalArticle

8 Citations (Scopus)

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-{β-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.

Original languageEnglish (US)
Pages (from-to)479-484
Number of pages6
JournalShock
Volume15
Issue number6
DOIs
StatePublished - Jan 1 2001

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Granulocyte Colony-Stimulating Factor
Lung
Wounds and Injuries
Lung Injury
Adenosine
Dimercaprol
Hemorrhagic Shock
Therapeutics
Resuscitation
Anti-Inflammatory Agents
Contusions
Bronchoalveolar Lavage
Chemotaxis
Reperfusion Injury
Leukocyte Count
Phagocytosis
Peroxidase
Ligation
Lipopolysaccharides
Proteins

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Davis, K. A., Fabian, T. C., Ragsdale, D. N., Trenthem, L. L., Croce, M., & Proctor, K. G. (2001). Combination therapy that targets secondary pulmonary changes after abdominal trauma. Shock, 15(6), 479-484. https://doi.org/10.1097/00024382-200115060-00012

Combination therapy that targets secondary pulmonary changes after abdominal trauma. / Davis, Kimberly A.; Fabian, Timothy C.; Ragsdale, D. Nicholas; Trenthem, Lisa L.; Croce, Martin; Proctor, Kenneth G.

In: Shock, Vol. 15, No. 6, 01.01.2001, p. 479-484.

Research output: Contribution to journalArticle

Davis, KA, Fabian, TC, Ragsdale, DN, Trenthem, LL, Croce, M & Proctor, KG 2001, 'Combination therapy that targets secondary pulmonary changes after abdominal trauma', Shock, vol. 15, no. 6, pp. 479-484. https://doi.org/10.1097/00024382-200115060-00012
Davis, Kimberly A. ; Fabian, Timothy C. ; Ragsdale, D. Nicholas ; Trenthem, Lisa L. ; Croce, Martin ; Proctor, Kenneth G. / Combination therapy that targets secondary pulmonary changes after abdominal trauma. In: Shock. 2001 ; Vol. 15, No. 6. pp. 479-484.
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