Nitric oxide involvement in the hemodynamic response to fluid resuscitation in endotoxic shock in rats

Losser, Marie-Reine; Forget, Anne-Pascale; Payen, Didier

doi:10.1097/01.ccm.0000231878.82244.c9

Cited by 30 publications

(16 citation statements)

References 43 publications

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“…1). 32 Endothelial NO synthase (eNOS)-derived NO prevents vascular dysfunction by a direct vasodilatory effect, by inhibiting platelet aggregation and leukocyte activation. Inhibitors blocking eNOS activity have been shown to exacerbate organ ischemia.…”

Section: Endothelial Dysfunction Nitric Oxide System and Oxidative mentioning

confidence: 99%

The Microcirculation of the Septic Kidney

Zafrani

Payen

Azoulay

et al. 2015

Seminars in Nephrology

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Section: Endothelial Dysfunction Nitric Oxide System and Oxidative mentioning

confidence: 99%

The Microcirculation of the Septic Kidney

Zafrani

Payen

Azoulay

et al. 2015

Seminars in Nephrology

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“…The demonstrated sepsis-induced endothelial dysfunction (38,39), particularly the decreased NO release from endothelial NOS, altered the fluid-induced vasodilation in vitro in isolated vessel preparations (40,41). In a rat model of endotoxemia, Losser et al (35) demonstrated that the endothelium participates in the hemodynamic response to fluid loading which occurs at least partially secondary to altered NO-dependent vasodilation. Pro-inflammatory cytokines such as TNF are also involved in this sepsis-induced vasodilation.…”

Section: Loss Of Vascular Tonementioning

confidence: 99%

“…Myocardial dysfunction does not appear to be due to myocardial hypoperfusion but instead to circulating depressant factors, including the cytokines TNF and IL-1b (32Á34). At a cellular level, reduced myocardial contractility seems to be induced by both nitric oxide-dependent and -independent mechanisms (35).…”

Section: Cardiac Dysfunctionmentioning

confidence: 99%

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Resuscitation volume and multiple organ dysfunction syndrome

Asehnoune

2009

Journal of Organ Dysfunction

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Patients with severe infections and major trauma often develop multiple organ dysfunction syndrome (MODS). Aggressive fluid resuscitation can be involved in such a process and several lines of evidence have demonstrated the detrimental effects of large crystalloid-based resuscitation strategies on MODS. Additionally, fluid-restrictive strategies have been associated with a decreased frequency of acute respiratory distress syndrome (and a shorter time to recover from it) and with trends toward a shorter length of hospital stay and lower mortality. Recent knowledge of the pathophysiology of septic shock and severe trauma indicates that a release of inflammatory mediators occurs early in the course of the disease. These mediators, especially pro-inflammatory cytokines as well as hypopituitary adrenal axis dysfunction, are involved in cardiac dysfunction and vasodilatation-induced hypotension. Taking into account this combination of severe inflammation and secondary changes in endocrine profile through an earlier use of vasopressors, inotropic drugs and/or hormones may help to achieve adequate hemodynamic goals without the need for aggressive fluid resuscitation. Studies are needed to integrate these new concepts into future guidelines regarding fluid resuscitation for hypotensive patients facing sepsis or severe trauma.

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“…This is an open field for research and discussion and probably has multiple answers some of which involving the understanding of the mechanisms behind the beneficial and detrimental effects of fluid resuscitation. Although several groups, including our own, have been studying the role of fluid resuscitation during sepsis, these mechanisms are not completely elucidated even though it is argued that they could be related to endothelium via the nitric oxide (NO) pathway [10-12]. …”

Section: Introductionmentioning

confidence: 99%

Fluid resuscitation therapy in endotoxemic hamsters improves survival and attenuates capillary perfusion deficits and inflammatory responses by a mechanism related to nitric oxide

2014

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BackgroundRelative hypovolemia is frequently found in early stages of severe sepsis and septic shock and prompt and aggressive fluid therapy has become standard of care improving tissue perfusion and patient outcome. This paper investigates the role of the nitric oxide pathway on beneficial microcirculatory effects of fluid resuscitation.MethodsAfter skinfold chamber implantation procedures and endotoxemia induction by intravenous Escherichia coli lipopolysaccharide administration (2 mg.kg−1), male golden Syrian hamsters were fluid resuscitated and then sequentially treated with L-Nω-Nitroarginine and L-Arginine hydrochloride (LPS/FR/LNNA group). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables including venular leukocyte rolling and adhesion. Macro-hemodynamic, biochemical and hematological parameters as well as survival rate were also evaluated. Endotoxemic hamsters treated with fluid therapy alone (LPS/FR group) and non-treated animals (LPS group) served as controls.ResultsFluid resuscitation was effective in reducing lipopolysaccharide-induced microcirculatory changes. After 3 hours of lipopolysaccharide administration, non-fluid resuscitated animals (LPS group) had the lowest functional capillary density (1% from baseline for LPS group vs. 19% for LPS/FR one; p <0.05). At the same time point, arteriolar mean internal diameter was significantly wider in LPS/FR group than in LPS one (100% vs. 50% from baseline). Fluid resuscitation also reduced leukocyte-endothelium interactions and sequestration (p <0.05 for LPS vs. LPS/FR group) and increased survival (median survival time: 2 and 5.5 days for LPS and LPS/FR groups, respectively; p <0.05). Nitric oxide synthase inhibition prevented these protective effects, while L-Arginine administration markedly restored many of them.ConclusionOur results suggest that the underlying mechanism of fluid therapy is the restoration of nitric oxide bioavailability, because inhibition of NOS prevented many of its beneficial effects. Nevertheless, further investigations are required in experimental models closer to conditions of human sepsis to confirm these results.

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Nitric oxide involvement in the hemodynamic response to fluid resuscitation in endotoxic shock in rats

Abstract: These results suggest that the endothelium participates in the hemodynamic response to fluid loading in control rats, but less in rats with septic shock, secondary to an altered nitric oxide-dependent vasodilation.

Cited by 30 publications

References 43 publications

The Microcirculation of the Septic Kidney

The Microcirculation of the Septic Kidney

Resuscitation volume and multiple organ dysfunction syndrome

Fluid resuscitation therapy in endotoxemic hamsters improves survival and attenuates capillary perfusion deficits and inflammatory responses by a mechanism related to nitric oxide

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