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Abstract

18 hours after sepsis, when compared to baseline values before the CLP procedure (29.9 ± 1.1% and 57.3 ± 1.6%, respectively; P<0.05). In contrast, treatment with AICAR significantly improved both fractional shortening (26.6 ± 3.4%) and ejection fraction (52.4 ± 5.9%) when compared to vehicle treatment (P<0.05). At Western blotting analysis, the beneficial effects of AICAR were associated with increased AMPK phosphorylation, as well as increase of nuclear expression of peroxisome proliferator-activated receptor-ϒ co-activator α (PGC-1α), a major regulator of mitochondrial function and biogenesis. Conclusions: Our data indicate that AICAR confers cardioprotective effects during experimental sepsis through activation of AMPK-dependent metabolic repair mechanisms. These findings can potentially lead to a new therapeutic strategy for prevention of cardiac dysfunction in sepsis.Learning Objectives: Red cell distribution width (RDW), a quantitative measure of the variability in size of erythrocytes, has been associated with an increased hospital mortality in critically ill patients. The reason for this association remains unclear, especially on rheology. We hypothezised that an increased RDW might contribute to microcirculatory alterations in sepsis. Methods:Analysis of prospectively collected database. Microcirculatory measurements were obtained either during severe sepsis (n = 27), or septic shock (n = 95). When multiple measurements were obtained, only the first was considered. Patients' demographics, comorbidities, the Acute Physiologic and Chronic Health Evaluation (APACHE) II score on admission and the Sequential Organ Failure Assessment (SOFA) score on the day of microcirculatory assessment were collected. The microcirculation of the sublingual area was evaluated using the Sidestream Dark-Field (SDF) videomicroscopy. RDW (normal ranges: 10.9-13.4%) was obtained retrospectively from routine blood analysis on the day of microcirculation evaluation. A sub-group analysis was performed after exclusion of patients with diabetes, heart failure, autoimmune disease, recent blood transfusion, cancer and haematological diseases, which can all influence RDW independently from critically illness. Data are presented as median [IQRs] Results: 122 patients were included. Median RDW on the day of microcirculation evaluation was 13.8 [12.8-15.5] and was within normal ranges in 48 (39%) patients. We found no correlation between RDW and microcirculatory parameters (functional capillary density, FCD -r = -0.12; proportion of small perfused vessels, PPV -r=0.17; mean flow index, MFI -r=-0.17). Also, no differences in FCD, PPV and MFI were found between patients with normal and altered RDW. Similar results were also found when the sub-group analysis was performed. We found not correlation of RDW with APACHE and SOFA scores. RDW values were not different between survivors and non-survivors. Conclusions: RDW was not associated with microcirculatory alterations or survival in septic patients.