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

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.

The Microcirculation of the Septic Kidney

“…Norepinephrine may have corrected this vascular tone, thus restoring normal capillary velocity and filtration pressure. 55 …”

“…SDF imaging has been used in rat models to monitor renal cortical peritubular capillary blood flow. 55 To this aim, the left kidney is exposed and an imaging camera is positioned on the surface. Special attention has to be paid to apply the lowest pressure on the kidney surface with the camera because pressure artifacts can induce a tamponade of microcirculatory flow patterns.…”

Physiological aspects of Toll‐like receptor 4 activation in sepsis‐induced acute kidney injury

“…Also, an impaired microcirculation in the peri-tubular capillary network has been described during endotoxemia in mice (Tiwari et al 2005, Wu et al 2007. Others report a peri-tubular hypervelocity of red blood cells (Burban et al 2013) during CLP-induced sepsis in rat with a reduction in GFR, which in turn was reversed with noradrenaline infusion. Peri-tubular capillary dysfunction is suggested to be an early feature of SI-AKI in mice after CLP .…”

“…Others report a peri‐tubular hypervelocity of red blood cells (Burban et al . ) during CLP‐induced sepsis in rat with a reduction in GFR, which in turn was reversed with noradrenaline infusion. Peri‐tubular capillary dysfunction is suggested to be an early feature of SI‐AKI in mice after CLP (Wang et al .…”

H2S during circulatory shock: Some unresolved questions

“…For example: lethal hypoxia [3], ischemia/reperfusion (I/R)-injury [4–30], cardiac arrest [31–36], hemorrhage and resuscitation [37–45], acute lung injury resulting from blunt chest trauma [46,47] and/or injurious mechanical ventilation [48–50], as well as systemic inflammation resulting from endotoxin injection [51–59], acute pancreatitis [60–63], polymicrobial sepsis [64–70], and/or burn injury [71–73]. While the beneficial effect of exogenous H 2 S supplementation and maintaining endogenous H 2 S production, respectively, are well-established in I/R injury, equivocal results were reported after cardiac arrest, hemorrhage and resuscitation, and, in particular, in sepsis: inhaling gaseous H 2 S [33,44,48,50,53,54,65], the injection of the sulfide-containing salts NaSH [31,39,49,51,59,63,64,66–71,120] and Na 2 S [32,34–38,41,42,44,47,48,72,73] or the slow-releasing H 2 S donor GYY4137 [55] as well as of inhibitors of H 2 S production [43,45,58–60,62,63,67–71,120] were associated with attenuation of shock-related organ dysfunction.…”