Renal macro- and microcirculation autoregulatory capacity during early sepsis and norepinephrine infusion in rats

Mélanie Burban,Alain Mercat,Jean-François Hamel,Mathilde De La Bourdonnaye,Nicolas Lerolle,Agnès Duveau,Maher Tabka,Paul Calès,Pierre Asfar

doi:10.1186/cc12818

Mélanie Burban, Alain Mercat + Show 7 more

Open Access

https://doi.org/10.1186/cc12818

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Abstract

IntroductionThe relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. Norepinephrine (NE) infusion may add another level of complexity.MethodsVentilated and anesthetized rats were submitted to various mean arterial pressure (MAP) steps by blood removal, in presence and absence of sepsis and/or NE. Renal blood flow (RBF) and blood velocity (Vm) in renal cortical capillaries (using Sidestream Dark Field Imaging) were measured. Data were analyzed using linear mixed models enabling us to display the effects of both the considered explanatory variables and their interactions.ResultsPositive correlations were found between MAP and RBF. Sepsis had no independent impact on RBF whereas norepinephrine decreased RBF, regardless of the presence of sepsis. The relationship between MAP and RBF was weaker above a MAP of 100 mmHg as opposed to below 100 mmHg, with RBF displaying a relative "plateau" above this threshold. Sepsis and NE impacted carotid blood flow (CBF) differently compared to RBF, demonstrating organ specificity. A positive relationship was observed between MAP and Vm. Sepsis increased Vm while nNE decreased Vm irrespective of MAP. Sepsis was associated with an increase in serum creatinine determined at the end of the experiments, which was prevented by NE infusion.ConclusionIn our model, sepsis at an early phase did not impact RBF over a large range of MAP. NE elicited a renal vasoconstrictive effect. Autoregulation of RBF appeared conserved in sepsis. Conversely, sepsis was associated with "hypervelocity" of blood flow in cortical peritubular capillaries reversed by NE infusion.

Highlights

The relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis
mean arterial pressure (MAP) had no significant effect on heart rate (HR) whereas sepsis and NE infusion were associated with a significant increase in HR
Langenberg et al reconciled these conflicting data by demonstrating that the main parameter that predicted renal blood flow (RBF) in the various published animal models was the maintenance of cardiac output through fluid loading [2]. We confirm these findings, as previously observed, after restoring normal MAP through fluid loading, RBF did not differ in the presence/absence of sepsis. We extend these data by showing that the relationship between MAP and RBF is not altered and that the relative RBF ‘plateau’ observed above a MAP of 100 mmHg, usually referred to as ‘autoregulation’ phenomenon, appeared to be preserved in sepsis or in the case of NE infusion [15]

Summary

Introduction

The relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. In animal models of sepsis, renal blood flow (RBF) is preserved provided that cardiac output is maintained with vascular fluid loading [2]. The abovementioned alterations in vasoreactivity may render the kidneys unable to protect themselves against additional ischemic insults during changes in systemic perfusion pressure: for instance, mean arterial pressure (MAP) variations may result in a rapid drop in RBF and/or glomerular filtration rate (GFR). Most animal studies on RBF in sepsis have used either no fluid loading leading to profound hemodynamic abnormalities or massive fluid resuscitation leading to ‘overcorrection’ of cardiac output and arterial pressure, such that the impact of variation of blood pressure over a range relevant to the human setting remains unknown [2]

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