Endogenous adenosine and secondary injury after chest trauma

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: No previous studies have examined actions of adenosine or related compounds after blunt chest trauma, but we have shown that the prototype adenosine-regulating agent, acadesine (aminoimidazole carboxamide ribonucleotide [AICAR]), has multiple favorable anti-inflammatory actions after other forms of trauma, ischemia, hemorrhage, and sepsis; and that a progressive inflammatory response in the contralateral (uninjured) lung after unilateral blunt chest trauma is caused (in part) by activation and sequestration of circulating leukocytes (white blood cells [WBCs]). Thus, we hypothesized that AICAR would ameliorate WBC-dependent, secondary pathophysiologic changes after blunt chest trauma. Methods: Mongrel pigs (28 ± 1 kg, n = 21) were anesthetized, mechanically ventilated, and injured on the right chest (pulmonary contusion) with a captive bolt gun. Either AICAR (1 mg/kg + 0.2 mg/kg/min) or its saline vehicle were administered for a 12-hour period, beginning 15 minutes before injury. Results: Injury caused a three- to fourfold increase in bronchoalveolar lavage (BAL) WBC counts, 10- to 20-fold increases in BAL protein, and 200% increases in lung edema as measured by wet-dry ratio (all p < 0.05), in both the injured (right) and the noninjured (left) lungs. With AICAR versus saline, BAL WBC counts, lung myeloperoxidase levels, and systemic hemodynamics were similar. However, the increases in BAL protein were attenuated by 30% to 50% (p < 0.14, NS) and edema was reduced (p < 0.05) in both lungs. Furthermore, oxygenation, hypercapnia, acidosis (all p < 0.05), and survival were improved (9 of 10 vs. 4 of 11, p < 0.04). Conclusion: Pretreatment with AICAR before experimental pulmonary contusion ameliorates the trauma-induced destruction of the alveolar capillary membrane, and attenuates the delayed secondary injury in the contralateral uninjured lung, by a mechanism that may be independent of leukocytes. Endogenous adenosine could have a role in the pathophysiologic response after blunt chest injury, with potential sites of action including the endothelium and alveolar macrophage. Adenosine-regulating agents may have therapeutic potential after blunt chest injury, but further studies are needed in clinically relevant models, with administration begun at the time of resuscitation.

Original languageEnglish
Pages (from-to)892-898
Number of pages7
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume49
Issue number5
StatePublished - Dec 27 2000
Externally publishedYes

Fingerprint

Thoracic Injuries
Adenosine
Lung
Wounds and Injuries
Bronchoalveolar Lavage
Leukocytes
Thorax
Nonpenetrating Wounds
Contusions
Leukocyte Count
Edema
Hypercapnia
Alveolar Macrophages
Firearms
Acidosis
Resuscitation
Peroxidase
Action Potentials
Endothelium
Sepsis

Keywords

  • Acute lung injury
  • Adenosine
  • Leukocyte
  • Swine
  • Trauma

ASJC Scopus subject areas

  • Surgery

Cite this

Davis, K. A., Fabian, T. C., Ragsdale, D. N., Trenthem, L. L., & Proctor, K. G. (2000). Endogenous adenosine and secondary injury after chest trauma. Journal of Trauma - Injury, Infection and Critical Care, 49(5), 892-898.

Endogenous adenosine and secondary injury after chest trauma. / Davis, Kimberly A.; Fabian, Timothy C.; Ragsdale, D. Nicholas; Trenthem, Lisa L.; Proctor, Kenneth G.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 49, No. 5, 27.12.2000, p. 892-898.

Research output: Contribution to journalArticle

Davis, KA, Fabian, TC, Ragsdale, DN, Trenthem, LL & Proctor, KG 2000, 'Endogenous adenosine and secondary injury after chest trauma', Journal of Trauma - Injury, Infection and Critical Care, vol. 49, no. 5, pp. 892-898.
Davis, Kimberly A. ; Fabian, Timothy C. ; Ragsdale, D. Nicholas ; Trenthem, Lisa L. ; Proctor, Kenneth G. / Endogenous adenosine and secondary injury after chest trauma. In: Journal of Trauma - Injury, Infection and Critical Care. 2000 ; Vol. 49, No. 5. pp. 892-898.
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