Research
Angiotensin II in experimental hyperdynamic sepsis
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* Corresponding author: Rinaldo Bellomo rinaldo.bellomo@austin.org.au
1 Howard Florey Institute, University of Melbourne, Grattan Street, Parkville, Melbourne, Victoria 3052, Australia
2 Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Burnett Building, Commercial Road, Prahran, Melbourne, Victoria, Australia
3 Department of Intensive Care and Department of Medicine, Austin Health, Studley Road, Heidelberg, Melbourne Victoria 3084, Australia
4 Department of Pharmacology, University of Melbourne, Grattan Street, Parkville, Melbourne, Victoria 3052, Australia
Critical Care 2009, 13:R190 doi:10.1186/cc8185
Published: 30 November 2009Abstract
Introduction
Angiotensin II (Ang II) is a potential vasopressor treatment for hypotensive hyperdynamic sepsis. However, unlike other vasopressors, its systemic, regional blood flow and renal functional effects in hypotensive hyperdynamic sepsis have not been investigated.
Methods
We performed an experimental randomised placebo-controlled animal study. We induced hyperdynamic sepsis by the intravenous administration of live E. coli in conscious ewes after chronic instrumentation with flow probes around the aorta and the renal, mesenteric, coronary and iliac arteries. We allocated animals to either placebo or angiotensin II infusion titrated to maintain baseline blood pressure.
Results
Hyperdynamic sepsis was associated with increased renal blood flow (from 292 +/- 61 to 397 +/- 74 ml/min), oliguria and a decrease in creatinine clearance (from 88.7 +/- 19.6 to 47.7 +/- 21.0 ml/min, P < 0.0001). Compared to placebo, Ang II infusion restored arterial pressure but reduced renal blood flow (from 359 +/- 81 ml/min to 279 +/- 86 ml/min; P < 0.0001). However, despite the reduction in renal blood flow, Ang II increased urine output approximately 7-fold (364 +/- 272 ml/h vs. 48 +/- 18 ml/h; P < 0.0001), and creatinine clearance by 70% (to 80.6 +/- 20.7 ml/min vs.46.0 +/- 26 ml/min; P < 0.0001). There were no major effects of Ang II on other regional blood flows.
Conclusions
In early experimental hypotensive hyperdynamic sepsis, intravenous angiotensin II infusion decreased renal blood while inducing a marked increase in urine output and normalizing creatinine clearance.