Ang II caused these renal changes without major adverse effects on blood flows to other vital organs, blood lactate or biochemical variables. These findings justify further investigations of Ang II in experimental and human sepsis.Key messages? Experimental hyperdynamic hypotensive sepsis former can be associated with renal vasodilatation and hyperemia while renal function becomes impaired? The combination of renal vasodilatation with decreased GFR suggests combined afferent and efferent arteriolar vasodilatation with greater arteriolar dilatation? Ang II infusion restores renal hemodynamic to normal? Ang II-induced restoration of intra-renal hemodynamics to normal is associated with improved creatinine clearance and a marked increase in urine output.
AbbreviationsAKI: acute kidney injury; Ang II: angiotensin II; CO: cardiac output; CVP: central venous pressure; FENa: fractional excretion of sodium; GFR: glomerular filtration rate; MAP: mean arterial pressure; RBF: renal blood flow.Competing interestsAs a result of this study, Drs. Clive May and Rinaldo Bellomo have applied for patent protection for the use of angiotensin II to treat septic acute kidney injury in man.Authors’ contributionsCNM, LW, CL and RB designed the study. LW and CNM performed the experiments and data analysis. All authors participated in the drafting of the final manuscript. All authors read and approved the final manuscript.AcknowledgementsThe authors are grateful to Craig Thomson (Funded by Howard Florey Institute) for excellent technical assistance. The study was supported by NHMRC Project grant No 454615.
This study was also supported by grant from the Australian and New Zealand College of Anaesthetists and Cilengitide from the Intensive Care Foundation. CNM was supported by NHMRC Research Fellowships No 350328 and 566819. Dr C. Langenberg was funded by Else Kr?ner-Fresenius Foundation (Germany).
During sepsis, the microcirculatory and mitochondrial dysfunction plays a key role in the development of severe sepsis, septic shock, and multiple organ failure [1]. This condition is characterized by microcirculatory perfusion heterogeneity, arteriovenous shunting, and impaired autoregulation mainly due to disturbed coagulation, inflammation, and leukocyte-endothelium interaction [1-3]. It is now well established in septic patients that restoring basic macrohemodynamic parameters, such as blood pressure, in itself does not lead to improved patient outcome, and that normalization of microcirculatory and mitochondrial function may be necessary as an endpoint [2,4].To this end, recombinant activated protein C (rh-aPC) has been used to restore the coagulative cascade, the inflammatory response, leukocyte adhesion and migration, and endothelial function.
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