Please use this identifier to cite or link to this item:
|Title:||Clonidine Restores Pressor Responsiveness to Phenylephrine and Angiotensin II in Ovine Sepsis.||Austin Authors:||Lankadeva, Yugeesh R;Booth, Lindsea C;Kosaka, Junko;Evans, Roger G;Quintin, Luc;Bellomo, Rinaldo ;May, Clive N||Affiliation:||1Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia
Department of Physiology, University of Lyon, Lyon, France.
6The Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia
5Department of Medicine, Austin Health, Heidelberg, Victoria, Australia
Department of Intensive Care, Austin Health, Heidelberg, Victoria, Australia
Department of Physiology, Monash University, Victoria, Australia
|Issue Date:||9-Apr-2015||Publication information:||Critical Care Medicine; 43(7): e221-9||Abstract:||In sepsis, prolonged, sympathetic overstimulation may lead to vasopressor-refractory hypotension. We therefore examined the effects of the α2-adrenergic agonist clonidine on mean arterial pressure, renal sympathetic nerve activity, and pressor responsiveness to phenylephrine and angiotensin II during hypotensive sepsis in conscious sheep.Interventional study.Research institute.Twelve adult Merino ewes (n = 6 per group).Sepsis was induced by IV infusion of Escherichia coli for 32 hours. Pressor responses to increasing doses of phenylephrine and angiotensin II were measured at baseline and at 24, 28, and 32 hours of sepsis. Sheep were treated with clonidine (1 μg/kg/hr) or saline-vehicle from 24 to 32 hours of sepsis.Sepsis was characterized by hypotension (~12 mm Hg), increased heart rate (~80 beats/min), increased renal sympathetic nerve activity (~70%), and blunted pressor responses to phenylephrine and angiotensin II. In vehicle-treated sheep, mean arterial pressure progressively declined from 25 to 32 hours of sepsis (73 ± 3 to 66 ± 3 mm Hg; p = 0.013) while the elevations in heart rate and renal sympathetic nerve activity and reduced pressor responsiveness to vasopressors persisted. Clonidine treatment prevented the further decline in mean arterial pressure, substantially reduced heart rate and renal sympathetic nerve activity and restored pressor responsiveness to both phenylephrine and angiotensin II toward preseptic levels.Administration of clonidine during hypotensive sepsis reduced renal sympathetic nerve activity, restored vascular sensitivity to both phenylephrine and angiotensin II, and resulted in better preservation of arterial pressure. Considering these findings, a clinical trial for the use of clonidine in the treatment of persistent vasopressor-refractory hypotension in patients with septic shock would be worthwhile.||Gov't Doc #:||25860204||URI:||http://ahro.austin.org.au/austinjspui/handle/1/12731||DOI:||10.1097/CCM.0000000000000963||URL:||https://pubmed.ncbi.nlm.nih.gov/25860204||Type:||Journal Article|
|Appears in Collections:||Journal articles|
Show full item record
checked on Dec 2, 2022
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.