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Tissue Inflammatory Responses in an Anesthetized Rat Hemorrhage Model Associated with Endothelial Dysfunction
Author(s) -
Dubick Michael A,
Torres Lucia,
Barr Johnny L,
Torres Filho Ivo P
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.837.20
Subject(s) - cremaster muscle , medicine , endocrinology , xanthine oxidase , skeletal muscle , oxidative stress , microcirculation , nitric oxide , albumin , inflammation , glutathione , lung , chemistry , endothelial dysfunction , resuscitation , anesthesia , biochemistry , enzyme
We have demonstrated endothelial dysfunction such as reduction in glycocalyx thickness and increased permeability in venules in cremaster muscle following hemorrhage and fluid resuscitation with a crystalloid or a colloid in a rat model. The present study further characterizes the model by measuring indices of inflammation and oxidative and nitrosative stress in tissues from these animals. Anesthetized Sprague‐Dawley rats (n=4–5/group) were bled 40% of their blood volume, subjected to a 30 min shock period and resuscitated with limited volumes of normal saline (NS) or 5% albumin (A), or no treatment (Hem). At 1hr after resuscitation, rats were euthanized and liver, kidney, lung and skeletal muscle were collected and assayed for cytokines and select indices of nitrosative and oxidative stress. In liver and kidney, IL‐1β, IL‐6 and TNF‐α levels were 2–3‐fold higher in the NS than the A group and about 2‐fold higher than the Hem group. IL‐10 levels were also significantly higher in the NS group than the other groups. Similar responses were observed in lung from these groups, while in muscle, only IL‐1β and IL‐6 levels were significantly higher. In contrast, no significant differences were observed in all tissues in nitric oxide, total antioxidant or reduced glutathione concentrations nor xanthine oxidase activity among the groups. In this model of hemorrhagic shock, NS induced the highest inflammatory response, while 5% albumin was associated with the least response. Interestingly, these current observations were related to the degree of endothelial dysfunction observed previously. Taken together these data suggest that the endothelial dysfunction observed in hemorrhagic shock and fluid resuscitation is associated with an inflammatory response without a major nitrosative or oxidative stress component. Support or Funding Information Funded by the US Army Medical Research Materiel Command