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Physiologic effects of low-level nutritional support in a mouse model of Klebsiella pneumoniae sepsis

Chuan, Byron (2020) Physiologic effects of low-level nutritional support in a mouse model of Klebsiella pneumoniae sepsis. Master's Thesis, University of Pittsburgh. (Unpublished)

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Sepsis is an illness characterized by high morbidity and mortality, accounting for 1 in 3 hospital deaths, affecting 1 - 3 million adults in the US every year. Among sepsis cases, approximately 12% are complicated by the incidence of hyperglycemia, a condition that is associated with worsened outcomes including higher mortality. Prior work in our lab has shown the association between the provision of early enteral nutritional support with attenuated inflammatory responses, preservation of euglycemia through heightened insulin sensitivity, and improved mean arterial blood pressure in a mouse model of LPS-induced endotoxemia. As this is a sterile and some would argue, unrealistic model of sepsis, the aim of this study was to see if these results could be observed in a bacteremic model of sepsis, with a focus on mortality as one of the primary outcomes.
Ten week old male B6 mice were infected with K. pneumoniae (strain ATCC 43816 2x104 CFUs) via oropharyngeal aspiration after implantation of catheters in the femoral artery and femoral vein or stomach. 24hr. post infection, mice were started on low-level infusions of either intravenous dextrose, enteral dextrose, or enteral saline. Blood was sampled at 24hr. intervals. Mice were sacrificed when blood pressure fell below 61mmHg for at least an hour, or at 72hr. post infection. BAL and tissue samples were then collected.
At 72hr., mice receiving enteral dextrose had a mortality rate of 27%, compared to 78% in the enteral saline group and 100% in the IV dextrose group. Mice receiving enteral dextrose also maintained euglycemia and cardiovascular homeostasis for the duration of the experiment, compared to IV dextrose mice who became hyperglycemic and hypotensive and enteral saline mice who trended towards hypoglycemia and hypotension. Metrics of inflammation and lung injury were also significantly different between groups in some outcomes.
The results of this study suggest the possible therapeutic benefits of early low-level nutritional support in cases of sepsis. Of public health significance, enteral dextrose therapy could be used to decrease the incidence and severity of post-sepsis complication development, specifically loss of muscular and neurological function. It is possible that this is clinically relevant and could have implications for treatment strategies in the future for sepsis.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Chuan, Byronbyc4@pitt.edubyc4
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMailliard, Robbierbm19@pitt.edurbm19
Committee MemberMartinson, Jeremyjmartins@pitt.edujmartins
Committee CoChairO'Donnell, Christopherodonnellcp@upmc.educpo2
Date: 29 January 2020
Date Type: Publication
Defense Date: 5 December 2019
Approval Date: 29 January 2020
Submission Date: 25 November 2019
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 66
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: physiology nutrition critical illness
Date Deposited: 29 Jan 2020 19:20
Last Modified: 29 Jan 2020 19:20


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