Increased poly(ADP-ribose) polymerase activity during porcine hemorrhagic shock is transient and predictive of mortality

David E. Skarda, Karson S. Putt, Paul J. Hergenrother, Kristine E. Mulier, Greg J. Beilman

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Aim of the study: The aim of our study was to compare poly(ADP-ribose) polymerase (PARP) activity levels in a porcine model of hemorrhagic shock and resuscitation. Materials and methods: We designed a prospective, comparative randomized survival study of hemorrhagic shock using 20 male Yorkshire-Landrace pigs (15-25 kg). In 16 pigs after splenectomy, we induced hemorrhagic shock to a mean arterial pressure of 50 mm Hg (∼35% bleed). Pigs were randomized to receive normotensive resuscitation (SBP 90 mm Hg), mild hypotensive resuscitation (SBP 80 mm Hg), moderate hypotensive resuscitation (SBP 65 mm Hg), or no resuscitation (n = 4 in each group). We also included a group of sham animals that were instrumented and had a splenectomy but not bled (n = 4). Muscle and liver biopsies were taken prior to hemorrhage, after 45 min of shock, and 8, 24, and 48 h after resuscitation. PARP activity levels in biopsies were measured using chemical quantitation of NAD+. Results: Irrespective of our resuscitation strategy or outcome, both muscle and liver PARP activity levels rose after 45 min of shock and then returned to baseline. Excluding our control animals, PARP activity levels were significantly higher during shock in non-survivors compared to survivors. Conclusions: In our model of porcine hemorrhagic shock, PARP activity levels increased during hemorrhagic shock. However, this increase in PARP activity levels was transient as they returned to baseline regardless of resuscitation strategy. Interestingly, PARP activity levels were significantly higher during hemorrhagic shock in non-survivors compared to survivors. These findings suggest that PARP activity may be a part of initial pathways leading from hemorrhagic shock to death.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalResuscitation
Volume75
Issue number1
DOIs
StatePublished - Oct 2007

Keywords

  • Hemorrhage
  • Outcome
  • Shock
  • Trauma

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