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Renal bioenergetics during early gram-negative mammalian sepsis and angiotensin II infusion

Abstract

Purpose

To measure renal adenosine triphosphate (ATP) (bioenergetics) during hypotensive sepsis with or without angiotensin II (Ang II) infusion.

Methods

In anaesthetised sheep implanted with a renal artery flow probe and a magnetic resonance coil around one kidney, we induced hypotensive sepsis with intravenous Escherichia coli injection. We measured mean arterial pressure (MAP), heart rate, renal blood flow RBF and renal ATP levels using magnetic resonance spectroscopy. After 2 h of sepsis, we randomly assigned sheep to receive an infusion of Ang II or vehicle intravenously and studied the effect of treatment on the same variables.

Results

After E. coli administration, the experimental animals developed hypotensive sepsis (MAP from 92 ± 9 at baseline to 58 ± 4 mmHg at 4 h). Initially, RBF increased, then, after 4 h, it decreased below control levels (from 175 ± 28 at baseline to 138 ± 27 mL/min). Despite decreased RBF and hypotension, renal ATP was unchanged (total ATP to inorganic phosphate ratio from 0.69 ± 0.02 to 0.70 ± 0.02). Ang II infusion restored MAP but caused significant renal vasoconstriction. However, it induced no changes in renal ATP (total ATP to inorganic phosphate ratio from 0.79 ± 0.03 to 0.80 ± 0.02).

Conclusions

During early hypotensive experimental Gram-negative sepsis, there was no evidence of renal bioenergetic failure despite decreased RBF. In this setting, the addition of a powerful renal vasoconstrictor does not lead to deterioration in renal bioenergetics.

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Acknowledgments

The authors are grateful to Tony Dornom and Craig Thomson for excellent technical assistance. This study was supported by a grant from NHMRC, Australia (454615) and by the Victorian Government through the Operational Infrastructure Scheme. KI was supported by a research fellowship from Iwate Medical University, and CNM was supported by a NHMRC Research Fellowship (566819).

Author information

Correspondence to Clive N. May.

Additional information

This article is discussed in the editorial available at: doi: 10.1007/s00134-012-2489-0.

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May, C.N., Ishikawa, K., Wan, L. et al. Renal bioenergetics during early gram-negative mammalian sepsis and angiotensin II infusion. Intensive Care Med 38, 886–893 (2012). https://doi.org/10.1007/s00134-012-2487-2

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Keywords

  • Acute kidney injury
  • Angiotensin II
  • Magnetic resonance spectroscopy
  • Renal blood flow
  • Septic shock