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

Abstract

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.

Effect of Dihydroquercetin on Energy Metabolism in LPS-Induced Inflammatory Mice

“…Then, with the peripheral tissues exhibiting a greater demand for blood glucose than there is a supply [ 52 ], the liver glycogen depletion and serum Glu decreased. Meanwhile, endotoxins also could induce microcirculation dysfunction in the body [ 53 ], and under conditions of cellular and tissue ischemia and hypoxia, anaerobic metabolism dominated, mitochondrial oxidative phosphorylation led to a dramatic decrease in ATP production [ 54 ], and the intracellular glycolysis energy supply mechanism was activated to maintain the energy supply, becoming one of the main sources of ATP [ 3 , 54 ]. Glycolytic metabolism was enhanced under conditions of low oxygen and high energy demand; thus, LDH increased.…”

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs

“…Several studies have described improved µflow in sepsis with systemically applied NO donors [13,14,15]. However, these results could not be reproduced in a clinical trial [16].…”

Effect of fluid resuscitation on acute lung injury in a rat model of sepsis

“…However, positive fl uid balance has also been shown to harm ARDS patients. Therefore, the key to treatment is to fi nd the balance between pulmonary edema while achieving improvement in tissue perfusion (35). So, we planned this study to investigate which fl uid is more effective in lung injury.…”

“…Shown in studies, HES was more effective than crystalloid solutions in reducing tissue expression of VEGF, capillary permeability, and lung edema levels (34). However, there was another study performed in a sheep model of peritonitis induced sepsis which showed that even though the albumin and HES could improve the cardiac output, delivery of oxygen and reduce the blood lactate levels, there was no change in survival when compared with the administration of the crystalloid, RL (35).…”