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Metabolomic profiling to characterize acute intestinal ischemia/reperfusion injury

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  • Rachel G Khadaroo
  • Thomas A Churchill
  • Victor Tso
  • Karen L Madsen
  • Chris Lukowski
  • Saad Y Salim

Abstract

Sepsis and septic shock are the leading causes of death in critically ill patients. Acute intestinal ischemia/reperfusion (AII/R) is an adaptive response to shock. The high mortality rate from AII/R is due to the severity of the disease and, more importantly, the failure of timely diagnosis. The objective of this investigation is to use nuclear magnetic resonance (NMR) analysis to characterize urine metabolomic profile of AII/R injury in a mouse model. Animals were exposed to sham, early (30 min) or late (60 min) acute intestinal ischemia by complete occlusion of the superior mesenteric artery, followed by 2 hrs of reperfusion. Urine was collected and analyzed by NMR spectroscopy. Urinary metabolite concentrations demonstrated that different profiles could be delineated based on the duration of the intestinal ischemia. Metabolites such as allantoin, creatinine, proline, and methylamine could be predictive of AII/R injury. Lactate, currently used for clinical diagnosis, was found not to significantly contribute to the classification model for either early or late ischemia. This study demonstrates that patterns of changes in urinary metabolites are effective at distinguishing AII/R progression in an animal model. This is a proof-of-concept study to further support examination of metabolites in the clinical diagnosis of intestinal ischemia reperfusion injury in patients. The discovery of a fingerprint metabolite profile of AII/R will be a major advancement in the diagnosis, treatment, and prevention of systemic injury in critically ill patients.

Suggested Citation

  • Rachel G Khadaroo & Thomas A Churchill & Victor Tso & Karen L Madsen & Chris Lukowski & Saad Y Salim, 2017. "Metabolomic profiling to characterize acute intestinal ischemia/reperfusion injury," PLOS ONE, Public Library of Science, vol. 12(6), pages 1-15, June.
    • Handle: RePEc:plo:pone00:0179326
    DOI: 10.1371/journal.pone.0179326
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    References listed on IDEAS

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    1. Arun Sreekumar & Laila M. Poisson & Thekkelnaycke M. Rajendiran & Amjad P. Khan & Qi Cao & Jindan Yu & Bharathi Laxman & Rohit Mehra & Robert J. Lonigro & Yong Li & Mukesh K. Nyati & Aarif Ahsan & Sha, 2009. "Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression," Nature, Nature, vol. 457(7231), pages 910-914, February.
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