Protective microcirculatory and anti-inflammatory effects of heparin on endotoxemic hamsters

Miranda, Marcos L.; Prota, Luiz Felipe M.; Silva, Maria Júlia B.; Sicuro, Fernando Lencastre; Furtado, Eliane; Santos, Ana Olimpia Maia Teixeira dos

doi:10.5935/medicalexpress.2014.03.06

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…ingly, microcirculatory recruitment appeared to be independent of the anticoagulant effects of these drugs (6,10,54,64,80). Despite microvascular improvement, none of these agents have consistently improved the outcome of septic patients in numerous clinical trials, but all significantly increased the risk of bleeding (44,80). Activated protein C was withdrawn from markets worldwide in the wake of a clinical trial showing that, compared with placebo, this agent did not significantly reduce mortality in patients with septic shock (89).…”

Section: No Synthase Modulationmentioning

confidence: 99%

Microcirculatory dysfunction in sepsis: pathophysiology, clinical monitoring, and potential therapies

Miranda

Balarini

Caixeta

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Abnormal microvascular perfusion, including decreased functional capillary density and increased blood flow heterogeneity, is observed in early stages of the systemic inflammatory response to infection and appears to have prognostic significance in human sepsis. It is known that improvements in systemic hemodynamics are weakly correlated with the correction of microcirculatory parameters, despite an appropriate treatment of macrohemodynamic abnormalities. Furthermore, conventional hemodynamic monitoring systems available in clinical practice fail to detect microcirculatory parameter changes and responses to treatments, as they do not evaluate intrinsic events that occur in the microcirculation. Fortunately, some bedside diagnostic methods and therapeutic options are specifically directed to the assessment and treatment of microcirculatory changes. In the present review we discuss fundamental aspects of septic microcirculatory abnormalities, including pathophysiology, clinical monitoring, and potential therapies.

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Section: No Synthase Modulationmentioning

confidence: 99%

Microcirculatory dysfunction in sepsis: pathophysiology, clinical monitoring, and potential therapies

Miranda

Balarini

Caixeta

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…These results provide evidence that WW-85 blocks NO production, thereby improving cardiovascular function and microcirculation. Miranda et al [ 42 ] investigated the effects of heparin on endotoxemia-related microcirculatory changes and compared them to those observed with the use of recombinant human activated protein C. Heparin decreased lipopolysaccharide-induced leukocyte rolling and arteriolar vasoconstriction; survival increased in treated vs. non-treated animals. Administration of heparin plus recombinant human activated protein C was associated with a significant attenuation of lipopolysaccharide-induced capillary perfusion deficits.…”

Section: Resultsmentioning

confidence: 99%

Cardiovascular effects of shock and trauma in experimental models. A review

Rocha-e-Silva¹

2015

Revista Brasileira De Cirurgia Cardiovascular

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Experimental models of human pathology are useful guides to new approaches towards improving clinical and surgical treatments. A systematic search through PubMed using the syntax (shock) AND (trauma) AND (animal model) AND (cardiovascular) AND ("2010/01/01"[PDat]: "2015/12/31"[PDat]) found 88 articles, which were reduced by manual inspection to 43 entries. These were divided into themes and each theme is subsequently narrated and discussed conjointly. Taken together, these articles indicate that valuable information has been developed over the past 5 years concerning endothelial stability, mesenteric lymph, vascular reactivity, traumatic injuries, burn and sepsis. A surviving interest in hypertonic saline resuscitation still exists.

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“…Several animal and human studies have suggested that heparin not only effectively prevents the coagulation mechanism in endotoxaemia, but also causes a variety of anti-inflammatory responses against infection. Human endotoxaemia experimental models have indicated that heparin can treat endotoxaemia by inducing coagulation activities (Jaimes et al, 2006;Li et al, 2009;Li et al, 2013;Miranda et al, 2014;Schiffer et al, 2002;Wyns et al, 2015;Zhao et al, 2017). However, in human models, the inhibition of inflammatory pathways following endotoxaemia has not been as clearly demonstrated as in animal Several animal and human trials have been conducted to investigate the possible benefits of heparin in the treatment of bacterial infections.…”

Section: Discussionmentioning

confidence: 99%

Un‐fractionated heparin counteracts the systemic inflammatory responses and multiple organ damages caused by endotoxaemia in sheep

Ashareyoun

Chalmeh

Pourjafar

2022

Veterinary Medicine & Sci

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Background: Endotoxaemia is believed to be a major cause of mortality and there are several therapeutic regimens for the treatment of this situation.Objectives: The present experimental study was conducted to evaluate acute phase response, cardiovascular and hepatorenal damages following the treatment of Ovine experimental endotoxaemia model employing unfractionated heparin (UFH). Materials and Methods:Twenty clinically healthy 1-year-old fat-tailed ewes were randomly divided into four equal groups, comprising UFH 200, UFH 400, Ctrl+ and Ctrl-. Lipopolysaccharide (LPS) from Escherichia coli serotype O55:B5 at 0.4 μg/kg was administered intravenously to the ewes. UFH (at 200 and 400 IU/kg) was administrated to the UFH 200 and UFH 400 groups, respectively. All the ewes were evaluated clinically before and 1.5, 3, 4.5, 6 and 24 hours after LPS injection. Blood samplings were also performed at those hours. We measured serum concentrations of haptoglobin, interferon-gamma, total antioxidant status, malondialdehyde, cardiac lactate dehydrogenase, cardiac troponin-I, total bilirubin, alanine transaminase and creatinine. Serum concentrations of acute phase response, cardiovascular, hepatic and renal biomarkers and clinical parameters increased significantly following the induction of endotoxaemia in the groups receiving LPS. Results:The significantly lowest concentrations of these parameters at hours 4.5 and 6 among the treatment groups belonged to the UFH 400 sheep.Conclusions: UFH could act as an anti-inflammatory mediator by decreasing inflammatory cytokines and acute phase proteins, modulating oxidative stress biomarkers and reducing multiple organ dysfunction following endotoxaemia in a dose-dependent manner. Furthermore, the anti-inflammatory effects of UFH at 400 IU/kg were significantly higher than another dose. This research examined the effect of two doses of UFH and higher doses may have more anti-inflammatory effects that require further studies.

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Protective microcirculatory and anti-inflammatory effects of heparin on endotoxemic hamsters

Cited by 6 publications

References 26 publications

Microcirculatory dysfunction in sepsis: pathophysiology, clinical monitoring, and potential therapies

Microcirculatory dysfunction in sepsis: pathophysiology, clinical monitoring, and potential therapies

Cardiovascular effects of shock and trauma in experimental models. A review

Un‐fractionated heparin counteracts the systemic inflammatory responses and multiple organ damages caused by endotoxaemia in sheep

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