KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Effects of Ubiquinol with Fluid Resuscitation following Hemorrhagic Shock

    Thumbnail
    View/Open
    Bennetts_ku_0099D_12851_DATA_1.pdf (2.075Mb)
    Issue Date
    2013-08-31
    Author
    Bennetts, Paul S.
    Publisher
    University of Kansas
    Format
    164 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Nursing
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
    Metadata
    Show full item record
    Abstract
    Abstract Hemorrhagic shock (HS) and fluid resuscitation triggers ischemia-reperfusion injury in cells and increases the production of reactive oxygen species (ROS) which are known to activate the intrinsic pathway of apoptosis and contribute to organ dysfunction.1 Ubiquinol is a potent free radical scavenger which is produced endogenously and functions as part of the mitochondrial respiratory chain.2 No study has been conducted to investigate the effects of ubiquinol related to HS. The overall aim of this study was to examine the effects of ubiquinol on leukocyte mitochondria and in the lungs, diaphragm, heart and kidneys as a supplemental treatment for HS. A randomized experimental design was used for this study. Adult male Sprague-Dawley rats (n = 20) were anesthetized and HS was induced by withdrawing 40% of the rat's blood volume to maintain a mean arterial pressure of 45-55 mmHg for 60 minutes. Following HS the rats were resuscitated with blood and lactated Ringer's (LR) with or without ubiquinol (1 mg per 100 g of body weight). The rats were monitored for 120 minutes, the animals were euthanized and the organs harvested. Leukocyte mitochondria superoxide (O2*⁻) was measured by flow cytometry using MitoSOX Red, a mitochondrial-targeted variant of the fluorescent probe hydroethidine. Superoxide levels were measured at baseline, end of HS and 120 minutes following fluid resuscitation. Arterial blood values were also recorded at these times. At the end of experiment, diaphragms were evaluated for hydrogen peroxide (H2O2) using the fluorescent probe dihydrofluorescein-diacetate (Hfluor). The lungs, diaphragm, heart, and kidneys were examined for percent of apoptotic nuclear membrane damage using a differential dye uptake method with acridine orange and ethidium bromide. No significant differences were found between groups with regard to the volume of blood removed, hemodynamic status or arterial blood values (p 0.05). Ubiquinol decreased leukocyte mitochondrial production of O2*⁻ at the end of the experiment by 35% compared to the control group (4687.2 ± 265.4 versus 7227.9 ± 534.5, p ˂ 0.001). Similarly, the mean fluorescence intensity (MFI) of diaphragm H2O2 was significantly lower in the ubiquinol group compared to control (4193 ± 333 versus 23513 ± 5098, p ˂ 0.001). The percent of apoptosis in the lungs, diaphragm, heart, and kidneys was significantly reduced in the animals treated with ubiquinol compared to the control group (6.0 ± 0.7% versus 39.2 ± 1.1%, 4.7 ± 0.5% versus 30.6 ± 2.4%, 2.9 ± 0.6% versus 23.6 ± 1.2%, 2.4 ± 0.3% versus 42.1± 1.9%, respectively, p ˂ 0.001). Ubiquinol was effective in decreasing leukocyte mitochondrial O2*⁻ formation, which suggests that ubiquinol scavenged O2*⁻ within the mitochondria. Since ubiquinol is a potent antioxidant, it also probably scavenged other free radicals outside the mitochondria. The increased concentration of ubiquinol within the mitochondria would assist in maintaining the activities within the electron transport chain during HS. In addition, the decreased mitochondrial O2*⁻ would result in lower H2O2 production. The significant reduction in the percent of apoptosis in lungs, diaphragm, heart and kidneys between the control and treatment rats, suggests that decreased ROS production attenuated the activation of the intrinsic (mitochondrial) apoptosis pathway.3 The findings could also be attributed to the stabilization of the mitochondrial membrane by ubiquinol, which has been demonstrated in a previous study.4 In conclusion, ubiquinol may have application as a supplemental treatment to reduce free radical damage and apoptosis- related injury following HS and fluid resuscitation.
    URI
    http://hdl.handle.net/1808/14848
    Collections
    • KU Med Center Dissertations and Theses [464]
    • Dissertations [4472]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps