Locations and mechanisms of leukocyte accumulation in the coronary microcirculation during reperfusion following ischemia

Persistent Link:
http://hdl.handle.net/10150/282173
Title:
Locations and mechanisms of leukocyte accumulation in the coronary microcirculation during reperfusion following ischemia
Author:
Ritter, Leslie Sue, 1952-
Issue Date:
1996
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:
Restoration of blood flow to the ischemic myocardium is the most effective approach to limit necrosis. However, it appears that the act of reperfusion causes additional tissue damage, and this condition is known as myocardial reperfusion injury. It is well established that leukocytes contribute to additional myocyte and vascular injury during reperfusion, and that this injury occurs within the first minutes of flow restoration. A great deal is known about the leukocyte contribution to myocardial reperfusion injury. However, the mechanisms under which leukocytes accumulate in the coronary microcirculation during early reperfusion are unclear. The purpose of these studies was to identify the mechanisms of leukocyte accumulation in the coronary microcirculation during early reperfusion following ischemia. Using direct visualization techniques, it was observed that leukocyte accumulation in coronary capillaries and venules during the first minutes of reperfusion differs with respect to the magnitude and persistence of accumulation. During reperfusion, significant leukostasis in coronary capillaries occurs in the absence of blood activation, and is significantly enhanced when the blood is activated and when the reperfusion blood flow is moderately reduced. Also, the results indicate that postischemic capillary leukostasis can be attenuated by increasing leukocyte deformability and by inhibition of P- and L-selectin adhesion molecules. In contrast, leukocyte adhesion to the coronary venules during reperfusion is not significantly increased when the blood is not activated and returned at full flow. However, leukocyte adhesion to the venules is enhanced when the blood is activated or when reperfusion blood flow is severely reduced. In addition, under conditions of low reperfusion blood flow, leukocyte adhesion to the venules is attenuated by P- and L-selectin adhesion molecule inhibition. In these experiments, leukocytes remained in the capillaries longer than they remained in the venules during reperfusion. These results indicate that the degree to which leukocyte accumulation occurs in postischemic capillaries and venules is dependent upon the conditions of reperfusion. The results of this study also suggest that attempts to limit early myocardial leukocyte-mediated reperfusion injury should consider leukocyte deformability, the state of activation of the leukocyte, reperfusion blood flow, and selectin-mediated adhesion events.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Animal Physiology.; Health Sciences, Medicine and Surgery.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
McDonagh, Paul F.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleLocations and mechanisms of leukocyte accumulation in the coronary microcirculation during reperfusion following ischemiaen_US
dc.creatorRitter, Leslie Sue, 1952-en_US
dc.contributor.authorRitter, Leslie Sue, 1952-en_US
dc.date.issued1996en_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.abstractRestoration of blood flow to the ischemic myocardium is the most effective approach to limit necrosis. However, it appears that the act of reperfusion causes additional tissue damage, and this condition is known as myocardial reperfusion injury. It is well established that leukocytes contribute to additional myocyte and vascular injury during reperfusion, and that this injury occurs within the first minutes of flow restoration. A great deal is known about the leukocyte contribution to myocardial reperfusion injury. However, the mechanisms under which leukocytes accumulate in the coronary microcirculation during early reperfusion are unclear. The purpose of these studies was to identify the mechanisms of leukocyte accumulation in the coronary microcirculation during early reperfusion following ischemia. Using direct visualization techniques, it was observed that leukocyte accumulation in coronary capillaries and venules during the first minutes of reperfusion differs with respect to the magnitude and persistence of accumulation. During reperfusion, significant leukostasis in coronary capillaries occurs in the absence of blood activation, and is significantly enhanced when the blood is activated and when the reperfusion blood flow is moderately reduced. Also, the results indicate that postischemic capillary leukostasis can be attenuated by increasing leukocyte deformability and by inhibition of P- and L-selectin adhesion molecules. In contrast, leukocyte adhesion to the coronary venules during reperfusion is not significantly increased when the blood is not activated and returned at full flow. However, leukocyte adhesion to the venules is enhanced when the blood is activated or when reperfusion blood flow is severely reduced. In addition, under conditions of low reperfusion blood flow, leukocyte adhesion to the venules is attenuated by P- and L-selectin adhesion molecule inhibition. In these experiments, leukocytes remained in the capillaries longer than they remained in the venules during reperfusion. These results indicate that the degree to which leukocyte accumulation occurs in postischemic capillaries and venules is dependent upon the conditions of reperfusion. The results of this study also suggest that attempts to limit early myocardial leukocyte-mediated reperfusion injury should consider leukocyte deformability, the state of activation of the leukocyte, reperfusion blood flow, and selectin-mediated adhesion events.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Animal Physiology.en_US
dc.subjectHealth Sciences, Medicine and Surgery.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMcDonagh, Paul F.en_US
dc.identifier.proquest9713411en_US
dc.identifier.bibrecord.b34403978en_US
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