Diagnose und Therapie der Sepsis

Reinhart, Konrad; Brunkhorst, Frank M.; Bone, Hans-Georg; Gerlach, Herwig; Gründling, Matthias; Kreymann, G.; Kujath, P.; Marggraf, G.; Mayer, Konstantin; Meier‐Hellmann, Andreas; Peckelsen, C.; Putensen, Christian; Stüber, Frank; Quintel, Michael; Ragaller, M.; Rossaint, Rolf; Weiler, Norbert; Welte, Tobias; Werdan, Karl

doi:10.1007/s00392-006-0414-7

Cited by 11 publications

(4 citation statements)

References 302 publications

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“…systemic inflammation, endothelial activation, impaired vasoregulation and intravascular volume depletion [12, 51–54]. In the present study, we demonstrate that mild hypothermia increases contractility in failing human myocardium.…”

Section: Discussionsupporting

confidence: 62%

Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium

et al. 2010

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Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of spontaneous circulation (ROSC) and contributes to hemodynamic instability and low survival rates after cardiac arrest. Mild hypothermia for 24 h after ROSC has been shown to significantly improve neurologic recovery and survival rates. In the present study we investigate the influence of therapeutic hypothermia on hemodynamic parameters in resuscitated patients and on contractility in failing human myocardium. We analyzed hemodynamic data from 200 cardiac arrest survivors during the hypothermia period. The initial LVEF was 32.6 ± 1.2% indicating a significantly impaired LV function. During hypothermia induction, the infusion rate of epinephrine could be significantly reduced from 9.1 ± 1.3 μg/min [arrival intensive care unit (ICU) 35.4°C] to 4.6 ± 1.0 μg/min (34°C) and 2.8 ± 0.5 μg/min (33°C). The dobutamine and norepinephrine application rates were not changed significantly. The mean arterial blood pressure remained stable. The mean heart rate significantly decreased from 91.8 ± 1.7 bpm (arrival ICU) to 77.3 ± 1.5 bpm (34°C) and 70.3 ± 1.4 bpm (33°C). In vitro we investigated the effect of hypothermia on isolated ventricular muscle strips from explanted failing human hearts. With decreasing temperature, the contractility increased to a maximum of 168 ± 23% at 27°C (n = 16, P < 0.05). Positive inotropic response to hypothermia was accompanied by moderately increased rapid cooling contractures as a measure of sarcoplasmic reticulum (SR) Ca2+ content, but can be elicited even when the SR Ca2+ release is blocked in the presence of ryanodine. Contraction and relaxation kinetics are prolonged with hypothermia, indicating increased Ca2+ sensitivity as the main mechanism responsible for inotropy. In conclusion, mild hypothermia stabilizes hemodynamics in cardiac arrest survivors which might contribute to improved survival rates in these patients. Mechanistically, we demonstrate that hypothermia improves contractility in failing human myocardium most likely by increasing Ca2+-sensitivity.Electronic supplementary materialThe online version of this article (doi:10.1007/s00392-010-0113-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 62%

Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium

et al. 2010

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“…We found that miR-let-7b expression was significantly decreased in septic mice compared with sham treated mice (p<0.0001, Figure 4A ). Sepsis is a kind of severe inflammatory host response diagnosed with inflammatory variables like leukocytosis (WBC counts above 12,000/μL) or leukopenia (WBC counts below 4,000/μL) ( 43 – 45 ). The more severe the septic inflammation, the closer the disease to sepsis shock, the lower the WBC level.…”

Section: Resultsmentioning

confidence: 99%

MicroLet-7b Regulates Neutrophil Function and Dampens Neutrophilic Inflammation by Suppressing the Canonical TLR4/NF-κB Pathway

et al. 2021

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Sepsis is a heterogeneous syndrome caused by a dysregulated host response during the process of infection. Neutrophils are involved in the development of sepsis due to their essential role in host defense. COVID-19 is a viral sepsis. Disfunction of neutrophils in sepsis has been described in previous studies, however, little is known about the role of microRNA-let-7b (miR-let-7b), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) activity in neutrophils and how they participate in the development of sepsis. In this study, we investigated the regulatory pathway of miR-let-7b/TLR4/NF-κB in neutrophils. We also explored the downstream cytokines released by neutrophils following miR-let-7b treatment and its therapeutic effects in cecal ligation and puncture (CLP)-induced septic mice. Six-to-eight-week-old male C57BL/6 mice underwent CLP following treatment with miR-let-7b agomir. Survival (n=10), changes in liver and lungs histopathology (n=4), circulating neutrophil counts (n=4), the liver-body weight ratio (n=4–7), and the lung wet-to-dry ratio (n=5–6) were recorded. We found that overexpression of miR-let-7b could significantly down-regulate the expression of human-derived neutrophilic TLR4 at a post-transcriptional level, a decreased level of proinflammatory factors including interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and an upregulation of anti-inflammatory factor IL-10 in vitro. After miR-let-7b agomir treatment in vivo, neutrophil recruitment was inhibited and thus the injuries of liver and lungs in CLP-induced septic mice were alleviated (p=0.01 and p=0.04, respectively), less weight loss was reduced, and survival in septic mice was also significantly improved (p=0.013). Our study suggested that miR-let-7b could be a potential target of sepsis.

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“…In Germany, for example, sepsis is the third most common cause of death after cardial infarction and neoplasms. 1 The treatment of sepsis is difficult and needs an interdisciplinary approach. Early diagnosis is necessary to slow the progression of organ dysfunction and improve the patient outcome.…”

Section: Introductionmentioning

confidence: 99%

Immunonutrition with Long-Chain Fatty Acids Prevents Activation of Macrophages in the Gut Wall

Eisner

Jacob

Frick

et al. 2011

Journal of Gastrointestinal Surgery

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Diagnose und Therapie der Sepsis

Cited by 11 publications

References 302 publications

Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium

Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium

MicroLet-7b Regulates Neutrophil Function and Dampens Neutrophilic Inflammation by Suppressing the Canonical TLR4/NF-κB Pathway

Immunonutrition with Long-Chain Fatty Acids Prevents Activation of Macrophages in the Gut Wall

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