Summary of study ST001390

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000953. The data can be accessed directly via it's Project DOI: 10.21228/M8HD6Z This work is supported by NIH grant, U2C- DK119886.

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Study IDST001390
Study TitleNatural history of the systemic responses to a renal inoculation of uropathogenic E. coli in swine
Study SummaryBackground: The pathogenesis of systemic infection and its progression to sepsis remains poorly understood. Progress in the field has been stifled by the shortcomings of experimental models which include poor replication of the human condition. To address these challenges, we developed a novel large animal model of systemic infection that is capable of generating high-dimensional clinically relevant data. Methods: Male swine (n=5) were anesthetized, mechanically ventilated, and surgically instrumented for continuous hemodynamic monitoring and serial blood sampling. Animals were inoculated with uropathogenic E. coli by direct injection into the renal parenchyma and were maintained under anesthesia for up to 24 hours. The natural history of the infection was studied, animals were not resuscitated. Multi-dimensional data were collected hourly to every 6 hours; all animals were euthanized when at predetermined physiologic endpoints. Results: Core body temperature progressively increased from mean (SD) 37.9(0.8) ̊C at baseline to 43.0(1.2) ̊C at experiment termination (p=0.006). While mean arterial pressure did not begin to decline until 6h post inoculation, dropping from 86(9) mmHg at baseline to 28(5) mmHg (p=0.005) at termination. Blood glucose progressively declined but lactate levels did not elevate until the last hours of the experiment. There were also temporal changes in whole blood concentrations of a number of metabolites including increases in the catecholamine precursors, tyrosine (p=0.005) and phenylalanine (p=0.005). Lung, liver, and kidney function parameters worsened as infection progressed and at study termination there was histopathological evidence of injury in these end-organs. Conclusion: We demonstrate a versatile, multi-dimensional, longitudinal, swine model of systemic infection that could be used to further our understanding of the mechanisms that underlie infection-induced multi-organ dysfunction and failure, optimize resuscitation protocols and test therapeutic interventions. Such a model could improve translation of findings from the bench to the bedside, circumventing a significant obstacle in sepsis research.
Institute
University of Michigan
Last NameFlott
First NameThomas
Address428 Church St., Ann Arbor, MI, 48109
EmailNMRmetabolomics@umich.edu
Phone7346604241
Submit Date2020-06-02
Raw Data AvailableYes
Raw Data File Type(s).fid
Analysis Type DetailNMR
Release Date2020-11-30
Release Version1
Thomas Flott Thomas Flott
https://dx.doi.org/10.21228/M8HD6Z
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000953
Project DOI:doi: 10.21228/M8HD6Z
Project Title:Natural History of the Systemic Responses to a Renal Inoculation of Uropathogenic E. coli in Swine
Project Summary:Metabolomics of whole blood samples from a novel large animal model of systemic infection.
Institute:University of Michigan
Last Name:Flott
First Name:Thomas
Address:428 Church St., Ann Arbor, MI, 48109
Email:NMRmetabolomics@umich.edu
Phone:7346604241
Contributors:Mohamad Hakam Tiba, Brendan M. McCracken, Robert P.Dickson, Jean A. Nemzek, Carmen I. Colmenero, Danielle C. Leander, Thomas L. Flott, Rodney C. Daniels, Kristine Konopka, J. Scott VanEpps, Kathleen A. Stringer, and Kevin R. Ward

Subject:

Subject ID:SU001464
Subject Type:Mammal
Subject Species:Sus Scrofa
Taxonomy ID:9823
Gender:Male

Factors:

Subject type: Mammal; Subject species: Sus Scrofa (Factor headings shown in green)

mb_sample_id local_sample_id Timepoint
SA113193224_024-
SA113194224_013-
SA113195224_009-
SA113196224_035-
SA113201224_09712
SA113202224_00112
SA113203224_02512
SA113204224_01012
SA113197224_0906
SA113198224_0206
SA113199224_0036
SA113200224_0796
Showing results 1 to 12 of 12

Collection:

Collection ID:CO001459
Collection Summary:Whole blood (WB) samples were collected from the indwelling line in the internal jugular vein. Blood was collected into 4ml Vacutainer tubes containing sodium heparin. Following collection, tubes were inverted several times to ensure adequate mixing and were immediately placed on ice. Each of two 600uL aliquots were added to screw-top cryogenic storage tubes and flash frozen in liquid nitrogen. Frozen samples were placed on dry ice until the completion of the experiment at which time they were transferred to storage in liquid nitrogen and stored until the time of assay. The remaining whole blood volume in the collection tube was centrifuged (1300g for 10 min at 4C). Aliquots of plasma(~600uL) were transferred into screw-top cryogenic storage tubes, flash frozen in liquid nitrogen, placed on dry ice, and stored in liquid nitrogen for future assays.
Sample Type:Blood (whole)
Storage Conditions:Described in summary

Treatment:

Treatment ID:TR001479
Treatment Summary:Male swine (n=5) were anesthetized, mechanically ventilated, and surgically instrumented for continuous hemodynamic monitoring and serial blood sampling. Animals were inoculated with uropathogenic E. coli by direct injection into the renal parenchyma and were maintained under anesthesia for up to 24 hours. The natural history of the infection was studied, animals were not resuscitated. Multi-dimensional data were collected hourly to every 6 hours; all animals were euthanized when at predetermined physiologic endpoints.

Sample Preparation:

Sampleprep ID:SP001472
Sampleprep Summary:Whole blood samples were thawed on ice and subjected to a methanol-chloroform precipitation. Briefly, samples were thawed in an ice-water bath after which 500 μL of blood was transferred to a microcentrifuge tube and 1ml of a 1:1 methanol-chloroform solution was added. Samples were sonicated for 2 minutes at 4°C, then incubated at -20°C for 20 minutes, and then centrifuged (13,400g at 4°C for 30 minutes). The aqueous supernatant was transferred to a new microcentrifuge tube and dried by lyophilization. Samples were then resuspended in 600 μL of 50mM sodium phosphate buffer in D2O for NMR analysis.
Processing Storage Conditions:On ice

Analysis:

Analysis ID:AN002319
Analysis Type:NMR
Num Factors:3
Num Metabolites:39
Units:uM

NMR:

NMR ID:NM000165
Analysis ID:AN002319
Instrument Name:Varian
Instrument Type:FT-NMR
NMR Experiment Type:1D-1H
Spectrometer Frequency:500 MHz
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