A randomised trial on the effect of anti-platelet therapy on the systemic inflammatory response in human endotoxaemia

Kiers, Dorien; Heijden, Wouter A van der; Ede, Lisa van; Gerretsen, Jelle; Mast, Quirijn de; Ven, A.J.A.M. van der; Messaoudi, Saloua El; Rongen, Gerard A.; Gomes, Marc E.; Kox, Matthijs; Pickkers, Peter; Riksen, Niels P.

doi:10.1160/th16-10-0799

Cited by 39 publications

(40 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…and cardiac output. This volume infusion is standard therapy in the local endotoxemia protocol to prevent vasovagal reactions [24]. Studies reporting enhanced dynamic cerebral autoregulation used a more conservative infusion regimen, with no additional fluid infusion prior to and during the entire experiment, versus approximately 2.5 L fluid infusion in our experiments [29].…”

Section: Discussionmentioning

confidence: 99%

“…Purified LPS (continuous infusion study: Escherichia coli O:113, Lot no. Bethesda, USA) was supplied as a lyophilized powder and dissolved in normal saline 0.9% as described previously [23,24]. For the continuous infusion study (c-LPS), a total of 4 ng/kg LPS was administered as a intravenous loading bolus of 1 ng/kg body weight at T = 0, followed by an intravenous infusion of 1 ng/kg/h for a period of 3 h [24].…”

Section: Experimental Human Endotoxemiamentioning

confidence: 99%

“…Bethesda, USA) was supplied as a lyophilized powder and dissolved in normal saline 0.9% as described previously [23,24]. For the continuous infusion study (c-LPS), a total of 4 ng/kg LPS was administered as a intravenous loading bolus of 1 ng/kg body weight at T = 0, followed by an intravenous infusion of 1 ng/kg/h for a period of 3 h [24]. For the bolus administration study (b-LPS), LPS was administered, as described previously, as an intravenous bolus injection at a dose of 2 ng/kg body weight in 1 min at T = 0 [23].…”

Section: Experimental Human Endotoxemiamentioning

confidence: 99%

“…All subjects received 1.5 L of 2.5% glucose/0.45% saline solution in the hour before initiation of LPS administration, followed by 150 mL/h during the first 6 h after LPS administration and 75 mL/h until the end of the experiment, according to our protocol [24].…”

Section: Experimental Human Endotoxemiamentioning

confidence: 99%

See 3 more Smart Citations

Dynamic Cerebral Autoregulation and Critical Closing Pressure in Experimental Human Endotoxemia and Sepsis Patients

2019

Med One

View full text Add to dashboard Cite

Background: To investigate the influence of systemic inflammation on dynamic cerebral autoregulation and vascular tone during experimental human endotoxemia and sepsis. Methods: Healthy volunteers received 3 h continuous infusion of LPS (c-LPS, 4 ng/kg, n = 11, Clinicaltrials.gov NCT02922673) or a bolus of LPS (b-LPS, 2 ng/kg, n = 8, Clinicaltrials.gov NCT02675868) and 10 sepsis patients were studied. Mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) were monitored simultaneously. Cerebral autoregulation was analysed by transfer function analysis (TFA). Critical closing pressure (CrCP) was estimated as a measure of cerebral vascular tone.Results: c-LPS resulted in a more pronounced and prolonged plasma cytokine response compared with b-LPS. MAP decreased from 89 ± 3 to 75 ± 2 mmHg (p < 0.05) and from 91 ± 2 to 77 ± 3 mmHg (p < 0.001) in the c-LPS and b-LPS groups, respectively. MAP in sepsis patients was 65 ± 4 mmHg. TFA in both LPS groups showed no significant changes over time in coherence, gain and phase. Phase in sepsis patients was lower compared with both LPS groups (7 (2 to 33) [median (interquartile range)] in sepsis versus 57 (36 to 74) in the c-LPS (p = 0.02) and 53 (43 to 64) degrees in the b-LPS group (p = 0.01)). CrCP decreased from 49 ± 2 to 41 ± 2 mmHg (p = 0.16) in the c-LPS and from 50 ± 2 to 42 ± 2 mmHg in the b-LPS group (p < 0.01), and was 36 ± 2 mmHg in sepsis patients. Conclusions:Dynamic cerebral autoregulation is impaired in sepsis patients, but remains intact during experimental human endotoxemia.CrCP decreased during endotoxemia and was low in sepsis, reflecting decreased vascular tone. This indicates activation of a cerebrovascular Open Access

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Experimental Human Endotoxemiamentioning

confidence: 99%

Section: Experimental Human Endotoxemiamentioning

confidence: 99%

Section: Experimental Human Endotoxemiamentioning

confidence: 99%

See 2 more Smart Citations

Dynamic Cerebral Autoregulation and Critical Closing Pressure in Experimental Human Endotoxemia and Sepsis Patients

2019

Med One

View full text Add to dashboard Cite

show abstract

“…With a deepening of their understanding of percutaneous coronary intervention (PCI), scholars have reached a consensus on the positive correction between post-PCI inflammation and restenosis, and methods for restenosis prevention via anti-inflammatory treatment have emerged. Anti-inflammation has become a new strategy for post-PCI restenosis prevention [11][12][13][14]. In recent years, an "endothelial-friendly" stent has been developed in which recombinant hirudin and iloprost are combined.…”

Section: Introductionmentioning

confidence: 99%

Effect of Paclitaxel+Hirudin on the TLR4-MyD88 Signaling Pathway During Inflammatory Activation of Human Coronary Artery Smooth Muscle Cells and Mechanistic Analysis

Li¹,

Wang²,

Xu³

2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Approximately 10%-20% of patients with acute cardiovascular disease who have received coronary intervention suffer restenosis and high inflammation. The stent compound paclitaxel+hirudin was prepared for the treatment of post-intervention restenosis. This study aimed to explore the anti-inflammatory and anti-restenosis mechanisms of paclitaxel+hirudin with regard to the TLR4/MyD88/NF-κB pathway. Methods: Human coronary artery smooth muscle cells (HCASMCs) at 4-6 generations after in vitro culture were used as a model. Lipopolysaccharide (LPS) was used as an inducer to maximally activate the TLR4/MyD88/NF-κB inflammation pathway. After MyD88 knockdown and selective blocking of MyD88 degradation with epoxomicin, the effects of paclitaxel+hirudin stenting on key sites of the TLR4/MyD88/NF-κB pathway were detected using ELISA, Q-PCR, and western blot analysis. Results: LPS at 1 μg/mL for 48 h was the optimal modeling condition for inflammatory activation of HCASMCs. Paclitaxel+hirudin inhibited the levels of key proteins and the gene expression, except for that of the MyD88 gene, of the TLR4-MyD88 pathway. The trend of the effect of paclitaxel+hirudin on the pathway proteins was similar to that of MyD88 knockdown. After epoxomicin intervention, the inhibitory effects of paclitaxel+hirudin on the key genes and proteins of the TLR4-MyD88 pathway were significantly weakened, which even reached pre-intervention levels. Paclitaxel+hirudin affected the MyD88 protein in a dosage-dependent manner. Conclusion: The paclitaxel+hirudin compound promotes MyD88 degradation in the TLR4/MyD88/NF-κB pathway to reduce the activity of TLR4 and NF-κB p65 and to weaken the LPS-initiated inflammatory reactions of IL-1β, IL-6, and TNF-α.

show abstract

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment

Gąsecka

Borovac

Guerreiro

et al. 2020

Cardiovasc Drugs Ther

121

120

View full text Add to dashboard Cite

Introduction Emerging evidence points to an association between severe clinical presentation of COVID-19 and increased risk of thromboembolism. One-third of patients hospitalized due to severe COVID-19 develops macrovascular thrombotic complications, including venous thromboembolism, myocardial injury/infarction and stroke. Concurrently, the autopsy series indicate multiorgan damage pattern consistent with microvascular injury. Prophylaxis, diagnosis and treatment COVID-19 associated coagulopathy has distinct features, including markedly elevated D-dimers concentration with nearly normal activated partial thromboplastin time, prothrombin time and platelet count. The diagnosis may be challenging due to overlapping features between pulmonary embolism and severe COVID-19 disease, such as dyspnoea, high concentration of D-dimers, right ventricle with dysfunction or enlargement, and acute respiratory distress syndrome. Both macro- and microvascular complications are associated with an increased risk of in-hospital mortality. Therefore, early recognition of coagulation abnormalities among hospitalized COVID-19 patients are critical measures to identify patients with poor prognosis, guide antithrombotic prophylaxis or treatment, and improve patients’ clinical outcomes. Recommendations for clinicians Most of the guidelines and consensus documents published on behalf of professional societies focused on thrombosis and hemostasis advocate the use of anticoagulants in all patients hospitalized with COVID-19, as well as 2-6 weeks post hospital discharge in the absence of contraindications. However, since there is no guidance for deciding the intensity and duration of anticoagulation, the decision-making process should be made in individual-case basis. Conclusions Here, we review the mechanistic relationships between inflammation and thrombosis, discuss the macrovascular and microvascular complications and summarize the prophylaxis, diagnosis and treatment of thromboembolism in patients affected by COVID-19.

show abstract

A randomised trial on the effect of anti-platelet therapy on the systemic inflammatory response in human endotoxaemia

Cited by 39 publications

References 49 publications

Dynamic Cerebral Autoregulation and Critical Closing Pressure in Experimental Human Endotoxemia and Sepsis Patients

Dynamic Cerebral Autoregulation and Critical Closing Pressure in Experimental Human Endotoxemia and Sepsis Patients

Effect of Paclitaxel+Hirudin on the TLR4-MyD88 Signaling Pathway During Inflammatory Activation of Human Coronary Artery Smooth Muscle Cells and Mechanistic Analysis

Thrombotic Complications in Patients with COVID-19: Pathophysiological Mechanisms, Diagnosis, and Treatment

Contact Info

Product

Resources

About