- 作者：Lonneke Smeding ; M.Sc.&lowast ; ; || ; l.smeding@vumc.nl ; Willem J. van der Laarse ; Ph.D.&dagger ; ; || ; Toke A. van Veelen ; M.Sc.&dagger ; ; Regis R. Lamberts ; Ph.D.¶ ; ; Hans W.M. Niessen ; M.D. ; Ph.D.&Dagger ; ; || ; Martin C.J. Kneyber ; M.D. ; Ph.D.|| ; # ; A.B. Johan Groeneveld ; M.D. ; Ph.D. ; F.C.C.P. ; F.C.C.M.§ ; ; || ; Frans B. Plö ; tz ; M.D. ; Ph.D.|| ; &lowast ; &lowast ;
- 关键词：sepsis ; myocardial inflammation ; mitochondrial function ; mitochondrial integrity ; mitochondrial biogenesis
- 刊名：Journal of Surgical Research
- 出版年：2012
- 期刊代码：299_00224804
- 类别：med
- 出版时间：July, 2012
- 卷：176
- 期：1
- 页码：178-184
- 文件大小：573 K
Background
Patients with complicated intra-abdominal infections are prone to develop multiple organ failure, including myocardial dysfunction. We hypothesized that early dysfunction during sepsis is associated with inflammation, mitochondrial injury, impaired mitochondrial function, and activation of mitochondrial biogenesis.Materials and Methods
Rats received lipopolysaccharide (LPS, n = 11) intraperitoneally. Healthy rats (n = 6) served as controls. Myocardial function was measured ex聽vivo in an isolated Langendorff-perfused heart set-up. Myocardial vascular cell adhesion molecule-1 (VCAM-1) expression was determined by immunofluorescence microscopy. Cytochrome c release and cytochrome c oxidase (COX IV) activity were measured by immunohistochemistry and enzyme histochemistry, respectively. Protein expression of tumor necrosis factor-伪 (TNF-伪), B-cell lymphoma (Bcl)-2, peroxisome proliferator activated receptor 纬 cofactor 1伪 (PGC-1伪), and mitochondrial transcription factor A (TFAM) were analyzed by Western blot technique. Mitochondria were studied by electron microscopy.
Results
Two hours after LPS injection, developed pressure had decreased and after 4 h myocardial contractility (+dP/dt) and relaxation (-dP/dt) also had decreased. TNF-伪 protein expression was increased after 2 h and returned to normal at 4 h, whereas after 4 h VCAM-1 expression was higher in LPS-treated animals. At 2 h a substrate-dependent increase in COXIV-activity was seen, but no mitochondrial damage occurred as cytochrome c release, COX IV activity and Bcl-2, PGC-1伪 or TFAM expression were not changed. Electron microscopy did not reveal differences in myocardial mitochondrial characteristics between LPS-treated and control rats.
Conclusions
Early myocardial dysfunction in sepsis is associated with myocardial inflammation but not with mitochondrial injury, impaired mitochondrial function, or activated mitochondrial biogenesis.