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.
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.
Early myocardial dysfunction in sepsis is associated with myocardial inflammation but not with mitochondrial injury, impaired mitochondrial function, or activated mitochondrial biogenesis.