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Oxidant-induced injury in the mammalian myocardium

Descriptive

TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Oxidant-induced injury in the mammalian myocardium
SubTitle
functional and molecular effects of acetaminophen
Identifier
ETD_2589
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000053099
Language
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Physiology and Integrative Biology
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Acetaminophen
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Myocardium--Diseases
Subject (ID = SBJ-4); (authority = ETD-LCSH)
Topic
Arrhythmia--Treatment
Abstract (type = abstract)
For over 100 years, acetaminophen (APAP) has been exclusively used as an efficacious antipyretic and analgesic. Here we report our ongoing investigation of the cardiovascular effects of APAP. In the first part of this study, we investigated the effects of 15 mg/kg APAP on hydrogen peroxide (H2O2)-induced canine myocardial dysfunction in vivo. Respiratory, metabolic, and hemodynamic indices such as left ventricular
function (LVDP and ±dP/dtmax), and percent ectopy were measured in anesthetized, openchest
dogs during intravenous administration of increasing doses of H2O2. Following 6.6 mM H2O2, tissue from the LV was harvested for electron microscopy. APAP-treated dogs regained greater fraction of baseline function after high concentrations of H2O2.
Moreover, the incidence of H2O2 -induced ventricular arrhythmias was reduced in APAP treated dogs. Additionally, electron micrograph images of left ventricular tissue confirmed preservation of tissue ultrastructure in APAP-treated hearts. In the second part of this study, we investigated the effects of APAP on
doxorubicin (DOX)-induced murine cardiac fibrosis in vivo, with a more detailed investigation of osteopontin (OPN) involvement using the H9c2 myocyte cell line in
vitro. We hypothesized that APAP would attenuate DOX-induced reactive oxygen species (ROS) and subsequent fibrosis via attenuation of increased cardiomyocyte OPN synthesis. In H9c2 cells, we found a dose-dependent decrease in cell viability at all
concentrations of DOX, which was attenuated by 50 μM APAP. Increased ROS was observed at all concentrations of DOX, which also was attenuated by APAP. A trend of DOX-induced increased OPN RNA synthesis was observed, and was significantly
decreased in the presence of APAP. Additionally, in WT and OPN-/- mice receiving four weekly injections of 4 mg/kg DOX ± APAP (30 mg/kg), we found increased fibrosis in groups receiving DOX as compared to those receiving DOX + APAP. Furthermore,
fibrosis in WT mice was higher than OPN-/- mice after DOX. Our results support the following conclusions: APAP is protective against (1) H2O2 –induced canine myocardial dysfunction, (2) H2O2 –induced arrhythmias, and (3) DOX injury by decreasing ROS, and
(4) lowering OPN RNA synthesis. (5) The absence OPN and presence of APAP decrease the severity of myocardial fibrosis due to DOX injury.
PhysicalDescription
Form (authority = gmd)
electronic resource
Extent
xi, 92 p. : ill.
InternetMediaType
application/pdf
InternetMediaType
text/xml
Note (type = degree)
Ph.D.
Note
Includes abstract
Note
Vita
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Kathryn Michelle Jaques
Name (ID = NAME-1); (type = personal)
NamePart (type = family)
Jaques
NamePart (type = given)
Kathryn Michelle
Role
RoleTerm (authority = RULIB)
author
DisplayForm
Kathryn Jaques
Name (ID = NAME-2); (type = personal)
NamePart (type = family)
Weiss
NamePart (type = given)
Harvey
Role
RoleTerm (authority = RULIB)
chair
Affiliation
Advisory Committee
DisplayForm
Harvey Weiss
Name (ID = NAME-3); (type = personal)
NamePart (type = family)
Denhardt
NamePart (type = given)
David
Role
RoleTerm (authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
David Denhardt
Name (ID = NAME-4); (type = personal)
NamePart (type = family)
Ma
NamePart (type = given)
Jianjie
Role
RoleTerm (authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Jianjie Ma
Name (ID = NAME-5); (type = personal)
NamePart (type = family)
Merrill
NamePart (type = given)
Gary
Role
RoleTerm (authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Gary Merrill
Name (ID = NAME-6); (type = personal)
NamePart (type = family)
Leone
NamePart (type = given)
Richard
Role
RoleTerm (authority = RULIB)
outside member
Affiliation
Advisory Committee
DisplayForm
Richard Leone
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (qualifier = exact)
2010
DateOther (qualifier = exact); (type = degree)
2010
Place
PlaceTerm (type = code)
xx
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3ZP466C
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (AUTHORITY = GS); (ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder (ID = PRH-1); (type = personal)
Name
FamilyName
Jaques
GivenName
Kathryn
Role
Copyright Holder
RightsEvent (ID = RE-1); (AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-04-13 19:19:48
AssociatedEntity (ID = AE-1); (AUTHORITY = rulib)
Role
Copyright holder
Name
Kathryn Jaques
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (ID = AO-1); (AUTHORITY = rulib)
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Technical

ContentModel
ETD
MimeType (TYPE = file)
application/pdf
MimeType (TYPE = container)
application/x-tar
FileSize (UNIT = bytes)
1515520
Checksum (METHOD = SHA1)
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