Macroscopic Postmortem Findings in 235 Surgical Intensive Care Patients with Sepsis

Torgersen, Christian; Moser, Patrizia; Luckner, Günter; Mayr, Viktoria D.; Jochberger, Stefan; Hasibeder, Walter; Dünser, Martin W.

doi:10.1213/ane.0b013e318195e11d

Cited by 208 publications

(161 citation statements)

References 21 publications

Supporting

Mentioning

148

Contrasting

Unclassified

Order By: Relevance

“…As known, lung tissue damage is observed in 90% of patients dying from sepsis and its associated complication (40). The histopathological features of lung injury in septic mice demonstrated here are resembled in the clinical condition of patients with sepsis (41).…”

Section: R E S E a R C H A R T I C L Esupporting

confidence: 67%

Stimulation of Brain AMP-Activated Protein Kinase Attenuates Inflammation and Acute Lung Injury in Sepsis

Mulchandani

Yang

Khan

et al. 2015

Mol Med

View full text Add to dashboard Cite

Sepsis and septic shock are enormous public health problems with astronomical financial repercussions on health systems worldwide. The central nervous system (CNS) is closely intertwined in the septic process but the underlying mechanism is still obscure. AMP-activated protein kinase (AMPK) is a ubiquitous energy sensor enzyme and plays a key role in regulation of energy homeostasis and cell survival. In this study, we hypothesized that activation of AMPK in the brain would attenuate inflammatory responses in sepsis, particularly in the lungs. Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV. The septic mice treated with AICAR exhibited elevated phosphorylation of AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle. Similarly, the expressions of TNF-α, IL-1β, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced. Moreover, histological findings in the lungs showed improvement of morphologic features and reduction of apoptosis with AICAR treatment. We further found that the beneficial effects of AICAR on septic mice were diminished in AMPKα2 deficient mice, showing that AMPK mediates these effects. In conclusion, our findings reveal a new functional role of activating AMPK in the CNS to attenuate inflammatory responses and acute lung injury in sepsis.

show abstract

Section: R E S E a R C H A R T I C L Esupporting

confidence: 67%

Stimulation of Brain AMP-Activated Protein Kinase Attenuates Inflammation and Acute Lung Injury in Sepsis

Mulchandani

Yang

Khan

et al. 2015

Mol Med

View full text Add to dashboard Cite

show abstract

“…Interestingly, post-mortem findings in surgical ICU patients who died from sepsis or septic shock revealed that in the majority of cases, a septic focus was still detectable even after treatment duration of 7 days (10). Histological analyses further confirmed a high rate of undetected or nonadequately addressed pulmonary or abdominal foci (10,11). Thus, the continuing presence of a pathologic trigger might contribute to the dramatic disease progress, leading to organ failure and death in these critically ill patients (12).…”

Section: Immunologic Dysfunctions Contribute To the High Mortalitymentioning

confidence: 80%

Why a second look might be worth it: immuno-modulatory therapies in the critically ill patient

et al. 2016

View full text Add to dashboard Cite

Sepsis and septic shock are associated with high mortality rates and remain a serious menace for the critically ill patient. Concurrent activation of pro-and anti-inflammatory pathways and an excessive cytokine release represent initial key features in the deregulation of the humoral and cellular antimicrobial defense. Research of the last decades addressed both the ebullient inflammation as well as the resulting longterm failure of the host immunity. While the reestablishment of an adequate immune-competence is still under investigation, many promising experimental trials to limit the inflammatory response during sepsis were challenged by missing beneficial effects in clinical studies. Nevertheless, due to advanced knowledge about the complex regulation of inflammatory mediators and their overlapping involvement in other potentially life-threatening diseases, further evaluation of these approaches in relevant subgroups could help to identify critically ill patients with potential benefit from anti-inflammatory therapies.

show abstract

“…One of the clinical manifestation of sepsis is the impairment and insufficiency of cardiac function. A previous study indicated that, among 235 patients who succumbed to sepsis or septic shock-associated mortality, those exhibiting cardiovascular system failure accounted for 35.3% (5). As the inflammatory reaction is important in sepsis, previous studies have attempted to use monoclonal antibodies raised against specific inflammatory factor receptors to inhibit the inflammatory reaction (2,6).…”

Section: Introductionmentioning

confidence: 99%

Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Zhou

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. The present study aimed to investigate the effects of bone marrow mesenchymal stem cells (MSCs) on the cardiac function and immune system of mice with endotoxemia. The mice were divided into the following groups: Control group, endotoxemia group, lipopolysaccharide (LPS) treatment group, LPS and MSC treatment group (LPS + MSC group) and MSC group. Following treatment with LPS, the cardiac function of the mice was examined at after 2, 6 and 24 h, and on day 7. An enzyme-linked immunofluorescent assay was used to analyze the serum and the levels of cytokines in the myocardium, and western blotting was used to investigate any changes in the levels of signaling proteins associated with the myocardium. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to investigate the growth rate of the splenic cells at after 24 h and on day 7, and the humoral immune function and phagocytosis of the macrophages in the mice were also examined. The cardiac function of the mice with endotoxemia declined, although this impairment was circumvented following treatment with MSCs. The levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and IL-10 in the serum and the myocardium increased following stimulation by LPS, although these declined as a result of MSC treatment. The expression levels of Toll-like receptor 4, p65-nuclear factor-κB and phosphorylated p38 in the mouse myocardium were enhanced following stimulation by LPS, which subsequently decreased as a result of MSC treatment. Compared with the control group, the growth rate of the splenic cells, humoral immune function and the level of phagocytosis of macrophages were all increased, although these parameters declined following treatment with MSCs. Taken together, the present study revealed that the MSCs inhibited the inflammatory reaction in the mice with endotoxemia, and improved cardiac function. By contrast, the cellular and humoral immunity were depressed, and phagocytosis of the macrophages, which were enhanced following simulation with LPS, were decreased following treatment with MSCs. However, no overexpression of the anti-inflammatory factor, IL-10, was observed. The present study hypothesized that MSCs exert a bifunctional role in endotoxemia, by inhibiting inflammatory factors, including IL-1 and IL-6, and inhibiting the compensatory expression of IL-10 following LPS stimulation. This avoids the possibility of excessive inhibition of immunological function, as this results in immunosuppression, and a higher ratio of IL-10 to TNF-α is indicative of a poor prognosis in patients with sepsis.

show abstract

Macroscopic Postmortem Findings in 235 Surgical Intensive Care Patients with Sepsis

Cited by 208 publications

References 21 publications

Stimulation of Brain AMP-Activated Protein Kinase Attenuates Inflammation and Acute Lung Injury in Sepsis

Stimulation of Brain AMP-Activated Protein Kinase Attenuates Inflammation and Acute Lung Injury in Sepsis

Why a second look might be worth it: immuno-modulatory therapies in the critically ill patient

Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Contact Info

Product

Resources

About