Angiotensin 1-7 in an experimental septic shock model.

Abstract

BACKGROUND:

Alterations in the renin-angiotensin system have been implicated in the pathophysiology of septic shock. In particular, angiotensin 1-7 (Ang-(1-7)), an anti-inflammatory heptapeptide, has been hypothesized to have beneficial effects. The aim of the present study was to test the effects of Ang-(1-7) infusion on the development and severity of septic shock.

METHODS:

This randomized, open-label, controlled study was performed in 14 anesthetized and mechanically ventilated sheep. Immediately after sepsis induction by bacterial peritonitis, animals received either Ang-(1-7) (n = 7) or placebo (n = 7) intravenously. Fluid resuscitation, antimicrobial therapy, and peritoneal lavage were initiated 4 h after sepsis induction. Norepinephrine administration was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg.

RESULTS:

There were no differences in baseline characteristics between groups. Septic shock was prevented in 6 of the 7 animals in the Ang-(1-7) group at the end of the 24-h period. Fluid balance and MAP were similar in the two groups; however, MAP was achieved with a mean norepinephrine dose of 0.4 μg/kg/min in the Ang-(1-7) group compared to 4.3 μg/kg/min in the control group. Heart rate and cardiac output index were lower in the Ang (1-7) than in the control group, as were plasma interleukin-6 levels, and creatinine levels. Platelet count and PaO2/FiO2 ratio were higher in the Ang-(1-7) group. Mean arterial lactate at the end of the experiment was 1.6 mmol/L in the Ang-(1-7) group compared to 7.4 mmol/L in the control group.

CONCLUSIONS:

In this experimental septic shock model, early Ang-(1-7) infusion prevented the development of septic shock, reduced norepinephrine requirements, limited interleukine-6 increase and prevented renal dysfunction.

• Authors: Bruno Garcia, Fuhong Su, Francesca Manicone, Laurence Dewachter, Raphaël Favory, Amina Khaldi, Alexander Moiroux-Sahroui, Anthony Moreau, Antoine Herpain, Jean-Louis Vincent, Jacques Creteur, Fabio Silvio Taccone, Filippo Annoni
• Journal: Critical care (London, England) (Crit Care) Vol. 27 Issue 1 Pg. 106 (03 13 2023) ISSN: 1466-609X [Electronic] England
• PMID: 36915144 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• Angiotensin I
• angiotensin I (1-7)
• Norepinephrine

Topics

• Animals
• Angiotensin I (pharmacology, therapeutic use)
• Norepinephrine (pharmacology, therapeutic use)
• Sepsis (drug therapy)
• Sheep
• Shock, Septic