Why do they die? Comparison of selected aspects of organ injury and dysfunction in mice surviving and dying in acute abdominal sepsis

被引：22
作者：
Drechsler S. [1 ]
Weixelbaumer K.M. [1 ,4 ]
Weidinger A. [1 ]
Raeven P. [1 ,2 ]
Khadem A. [1 ]
Redl H. [1 ]
van Griensven M. [1 ,5 ]
Bahrami S. [1 ]
Remick D. [3 ]
Kozlov A. [1 ]
Osuchowski M.F. [1 ]
机构：
[1] Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Trauma Research Center of AUVA, Donaueschingenstrasse 13, Vienna
[2] Department of Anaesthesia, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg
[3] Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, 02118, MA
[4] Current address: ViruSure GmbH, University of Veterinary Medicine Vienna, Veterinärplatz 1, Vienna
[5] Current address: Experimental Trauma Surgery, Clinic for Trauma Surgery, Klinikum Rechts der Isar, Technical University Munich, Ismaninger Straße 22, Munich
来源：
Intensive Care Medicine Experimental | / 3卷 / 1期
关键词：
Body temperature; Inflammation; Organ failure; Outcome prediction; Survival;
D O I：
10.1186/s40635-015-0048-z
中图分类号：
学科分类号：
摘要：
Background: The mechanisms of sepsis mortality remain undefined. While there is some evidence of organ damage, it is not clear whether this damage alone is sufficient to cause death. Therefore, we aimed to examine contribution of organ injury/dysfunction to early deaths in the mouse abdominal sepsis. Methods: Female OF-1 mice underwent either medium-severity cecal ligation and puncture (CLP-Only) or non-lethal CLP-ODam (CLP with cisplatin/carbontetrachloride to induce survivable hepatotoxicity and nephrotoxicity). In the first experiment, blood was collected daily from survivors (SUR; CLP-Only and CLP-ODam groups) or until early death (DIED; CLP-Only). In the second experiment (CLP-Only), early outcome was prospectively predicted based on body temperature (BT) and pairs of mice predicted to survive (P-SUR) and die (P-DIE) were sacrificed post-CLP. The overall magnitude of organ injury/dysfunction was compared in retrospectively and prospectively stratified mice. Results: At day 7 post-CLP, survival in CLP-Only was 48%, while CLP-ODam was non-lethal. In CLP-Only mice within 24 h of death, urea increased to 78 (versus 40 mg/dl in SUR), ALT to 166 (vs. 108 U/l), LDH to 739 (vs. 438 U/l) and glucose declined to 43 (vs. 62 mg/dl). In CLP-ODam, hypoglycemia was exacerbated (by 1.5-fold) and ALT and LDH were 20- and 8-fold higher versus DIED (CLP-Only) mice. In CLP-Only, predicted deaths (P-DIE) were preceded by a significant rise only in cystatin C (268 vs. 170 ng/ml in P-SUR) but not in creatinine and troponin I. Respiratory function of mitochondria in the liver and kidney of P-SUR and P-DIE CLP-Only mice was not impaired (vs. controls) and ATP level in organs remained similar among all groups. Histologic injury scores in the liver, kidney, heart and lung showed no major disparities among dying, surviving and control mice. Conclusions: In CLP-Only mice, although the deregulation of parameters indicative of organ injury/dysfunction was greater in dying versus surviving mice, it never exceeded the changes in surviving CLP-ODam animals, and it was not followed by histopathological damage and/or mitochondrial dysfunction. This shows that interpretation of the contribution of the organ injury/dysfunction to early deaths in the CLP model is not straightforward and depends on the pathophysiological origin of the profiled disturbances. © 2015, Drechsler et al.; licensee Springer.
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页码：1 / 21
页数：20
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