Pathophysiology of Septic Shock

Russell, James A.; Rush, Barret; Boyd, John H.

doi:10.1016/j.ccc.2017.08.005

Cited by 106 publications

(92 citation statements)

References 121 publications

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“…Vasoconstriction is a common safety concern of HBOCs which could be reflected by SVRI. Our results showed that SVRI was significantly decreased in sepsis rats, which is consistent with previous reports [20,21]. YQ23 and whole blood resulted in a gradual and gentle increase of SVRI ( Figure 5B), and there was no significant difference between YQ23 and WB group.…”

Section: Side Effects Of Yq23 In Sepsis Ratssupporting

confidence: 93%

A novel cross-linked haemoglobin-based oxygen carrier is beneficial to sepsis in rats

Kuang

Zhu

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Pathological hypoxia-induced organ dysfunction contributes to the high mortality of sepsis. Because of the microcirculation dysfunction following severe sepsis, it is difficult for erythrocytes to transport oxygen to hypoxic tissues. Haemoglobin-based oxygen carriers (HBOCs) are capable of delivering oxygen to hypoxic tissues. The aim of this study is to observe the potential benefits of a novel bovinederived, non-polymerized, cell-free HBOC solution, YQ23, on sepsis in rats. Cecum ligation and puncture was performed to induce sepsis in Sprague-Dawley rats. Effects of Lactate Ringer's solution (LR), YQ23, and whole blood on oxygen delivery and consumption, mitochondrial function, organ protection and animal survival were observed. LR failed to restore oxygen delivery and the therapeutic effects were limited, whereas low dosage of YQ23 and whole blood significantly increased the tissue oxygen delivery and consumption, improved the mitochondrial function of heart, liver, kidney and intestine, prevented the vital organs injuries and improved the animal survival. The effects of 0.15 gÁkg À1 YQ23 resembled that of the whole blood. In addition, YQ23 did not induce renal toxicity, severe oxidative effect and acute vasoconstriction. Thus, YQ23 is a safe and effective resuscitation fluid for sepsis. ARTICLE HISTORY

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Section: Side Effects Of Yq23 In Sepsis Ratssupporting

confidence: 93%

A novel cross-linked haemoglobin-based oxygen carrier is beneficial to sepsis in rats

Kuang

Zhu

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection (21,22), which frequently manifests an initial hyper-inflammatory phase, reflected by fever, shock, and respiratory failure (23). If patients survive the initial phase and sepsis persists, they enter a phase of immunosuppression (22,24,25).…”

Section: Introductionmentioning

confidence: 99%

Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response

Jennings

Nelson

et al. 2020

Front. Immunol.

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Alcohol differentially affects human health, depending on the pattern of exposure. Moderate intake provides beneficial mood modulation and an anti-inflammatory effect, while excessive consumption leads to immunosuppression and various alcohol use disorders. The mechanism underlying this bi-phasic action mode of alcohol has not been clearly defined. Our previous publication demonstrated that ethanol, in the absence of glucocorticoids (GCs), induces expression of Glucocorticoid-Induced Leucine Zipper (GILZ), a key molecule that transduces GC anti-inflammatory effect through a non-canonical activation of glucocorticoid receptor (1). Here we report that similar short-chain alcohols, such as ethanol, propanol and isopropanol, share the same property of upregulating GILZ gene expression, and blunt cell inflammatory response in vitro. When mice were exposed to these alcohols, GILZ gene expression in immune cells was augmented in a dose-dependent manner. Monocytes and neutrophils were most affected. The short-chain alcohols suppressed host inflammatory response to lipopolysaccharide (LPS) and significantly reduced LPS-induced mortality. Intriguingly, propanol and isopropanol displayed more potent protection than ethanol at the same dose. Inhibition of ethanol metabolism enhanced the ethanol protective effect, suggesting that it is ethanol, not its derivatives or metabolites, that induces immune suppression. Taken together, short-chain alcohols per se upregulate GILZ gene expression and provide immune protection against LPS toxicity, suggesting a potential measure to counter LPS septic shock in a resource limited situation.

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“…The cytokine-induced upregulation of adhesion molecules on the endothelium (intracellular adhesion molecule [ICAM] and vascular cell adhesion molecule 1 [VCAM-1]) and neutrophils (selectins) promotes the adhesion and diapedesis of neutrophils and the consequent release of proteases and ROS [13]. These substances, in association with the effects of iNOS (the loss of inhibitory effects on platelet and neutrophil activation, mediated by endothelial NOS) contribute to denudation of glycocalyx, further exposure of adhesion molecules, and impairment in endothelial barrier function [12].…”

Section: Organism Toxicity In Septic Shockmentioning

confidence: 99%

The Understanding and Management of Organism Toxicity in Septic Shock

Genga¹,

Shimada²,

Boyd

et al. 2018

J Innate Immun

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The toxicity caused by different organisms in septic shock is substantially complex and characterized by an intricate pathogenicity that involves several systems and pathways. Immune cells’ pattern recognition receptors initiate the host response to pathogens after the recognition of pathogen-associated molecular patterns. In essence, the subsequent activation of downstream pathways may progress to infection resolution or to a dysregulated host response that represents the hallmark of organ injury in septic shock. Likewise, the management of organism toxicity in septic shock is complicated and comprises a multiplicity of suitable targets. In this review, the classic immune responses to pathogens are discussed as well as other factors that are relevant in the pathogenicity of septic shock, including sepsis-induced immune suppression, inflammasome activation, intestinal permeability, and the role of lipids and proprotein convertase subtilisin/kexin type 9. Current therapies aiming to eliminate the organisms causing septic shock, recent and ongoing trials in septic shock treatment, and potential new therapeutic strategies are also explored.

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Pathophysiology of Septic Shock

Cited by 106 publications

References 121 publications

A novel cross-linked haemoglobin-based oxygen carrier is beneficial to sepsis in rats

A novel cross-linked haemoglobin-based oxygen carrier is beneficial to sepsis in rats

Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response

The Understanding and Management of Organism Toxicity in Septic Shock

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