The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats

Abstract

PurposeTo study the role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats.MethodsRats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 6), a group in which LPS administration was followed by immediate fluid resuscitation which prevented the drop of renal blood flow (EARLY group) (n = 6), and a group in which LPS administration was followed by delayed (i.e., a 2-h delay) fluid resuscitation (LATE group) (n = 6). Renal blood flow was measured using a transit-time ultrasound flow probe. Microvascular perfusion and oxygenation distributions in the renal cortex were assessed using laser speckle imaging and phosphorimetry, respectively. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were measured as markers of systemic inflammation. Furthermore, renal tissue samples were stained for leukocyte infiltration and inducible nitric oxide synthase (iNOS) expression in the kidney.ResultsLPS infusion worsened both microvascular perfusion and oxygenation distributions. Fluid resuscitation improved perfusion histograms but not oxygenation histograms. Improvement of microvascular perfusion was more pronounced in the EARLY group compared with the LATE group. Serum cytokine levels decreased in the resuscitated groups, with no difference between the EARLY and LATE groups. However, iNOS expression and leukocyte infiltration in glomeruli were lower in the EARLY group compared with the LATE group.ConclusionsIn our model, prevention of endotoxemia-induced systemic hypotension by immediate fluid resuscitation (EARLY group) did not prevent systemic inflammatory activation (IL-6, IL-10, TNF-α) but did reduce renal inflammation (iNOS expression and glomerular leukocyte infiltration). However, it could not prevent reduced renal microvascular oxygenation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-011-2267-4) contains supplementary material, which is available to authorized users.