Oxygen radicals and liver injury in hemorrhagic shock and resuscitation.

Persistent Link:
http://hdl.handle.net/10150/185420
Title:
Oxygen radicals and liver injury in hemorrhagic shock and resuscitation.
Author:
Dart, Richard Charles
Issue Date:
1991
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Hemorrhagic shock is a clinical syndrome involving widespread cellular dysfunction and resulting in injury to many organs. Resuscitation from hemorrhagic shock is similar to reperfusion after ischemia, but differs in that some blood flow persists during shock. Ischemia-reperfusion produces oxygen radicals in many organs, including the liver of the rat and the human. The hypothesis of this project was that oxygen radicals are produced and cause hepatic injury during resuscitation from hemorrhagic shock. The production of oxygen radicals within the liver should cause lipid peroxidation and tissue injury. Manipulation of defenses against oxygen radicals should decrease the hepatic injury caused by hemorrhagic shock and resuscitation. The blood pressure of Sprague-Dawley rats was reduced to 35-40 mm Hg by blood withdrawal for two hours, followed by reinfusion of withdrawn blood. Plasma alanine aminotransferase (ALT) levels rose and injury to hepatocytes and non-parenchymal cells was found on transmission electron microscopy. The presence of lipid peroxidation was determined by quantitation of ethane exhalation and hepatic content of thiobarbituric acid reactive substances (TBARS). Ethane exhalation was elevated during the hypotensive phase and after resuscitation. Hepatic TBARS levels were elevated after resuscitation only. The same hemorrhagic shock protocol was used to determine the effect of antioxidant manipulation on hepatic injury. The antioxidants superoxide dismutase, catalase, or deferoxamine produced no reduction in hepatic injury. The administration of phorone reduced hepatic non-protein sulfhydryl content and increased plasma ALT levels nine fold at 24 hours after resuscitation. The development of lipid peroxidation and the exacerbation of liver injury by the administration of phorone suggest that oxygen radicals are produced in the liver during hemorrhagic shock and resuscitation. However, the administration of antioxidants provided no protection. Therefore, it seems unlikely the oxygen radicals are involved in the pathogenesis of liver injury in this model. It is possible that the lipid peroxidation occurs after the cell is irreversible injured.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Dissertations, Academic; Hemorrhagic shock; Molecular biology -- Research
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Liebler, Daniel

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleOxygen radicals and liver injury in hemorrhagic shock and resuscitation.en_US
dc.creatorDart, Richard Charlesen_US
dc.contributor.authorDart, Richard Charlesen_US
dc.date.issued1991en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractHemorrhagic shock is a clinical syndrome involving widespread cellular dysfunction and resulting in injury to many organs. Resuscitation from hemorrhagic shock is similar to reperfusion after ischemia, but differs in that some blood flow persists during shock. Ischemia-reperfusion produces oxygen radicals in many organs, including the liver of the rat and the human. The hypothesis of this project was that oxygen radicals are produced and cause hepatic injury during resuscitation from hemorrhagic shock. The production of oxygen radicals within the liver should cause lipid peroxidation and tissue injury. Manipulation of defenses against oxygen radicals should decrease the hepatic injury caused by hemorrhagic shock and resuscitation. The blood pressure of Sprague-Dawley rats was reduced to 35-40 mm Hg by blood withdrawal for two hours, followed by reinfusion of withdrawn blood. Plasma alanine aminotransferase (ALT) levels rose and injury to hepatocytes and non-parenchymal cells was found on transmission electron microscopy. The presence of lipid peroxidation was determined by quantitation of ethane exhalation and hepatic content of thiobarbituric acid reactive substances (TBARS). Ethane exhalation was elevated during the hypotensive phase and after resuscitation. Hepatic TBARS levels were elevated after resuscitation only. The same hemorrhagic shock protocol was used to determine the effect of antioxidant manipulation on hepatic injury. The antioxidants superoxide dismutase, catalase, or deferoxamine produced no reduction in hepatic injury. The administration of phorone reduced hepatic non-protein sulfhydryl content and increased plasma ALT levels nine fold at 24 hours after resuscitation. The development of lipid peroxidation and the exacerbation of liver injury by the administration of phorone suggest that oxygen radicals are produced in the liver during hemorrhagic shock and resuscitation. However, the administration of antioxidants provided no protection. Therefore, it seems unlikely the oxygen radicals are involved in the pathogenesis of liver injury in this model. It is possible that the lipid peroxidation occurs after the cell is irreversible injured.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectDissertations, Academicen_US
dc.subjectHemorrhagic shocken_US
dc.subjectMolecular biology -- Researchen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorLiebler, Danielen_US
dc.contributor.committeememberSipes, I. Glennen_US
dc.contributor.committeememberBrendel, Klausen_US
dc.contributor.committeememberMayersohn, Michaelen_US
dc.contributor.committeememberAposhian, H. Vaskenen_US
dc.identifier.proquest9123472en_US
dc.identifier.oclc709778100en_US
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