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Objectives:

In sepsis, prolonged, sympathetic overstimulation may lead to vasopressor-refractory hypotension. We therefore examined the effects of the α 2-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.

Design:

Interventional study.

Setting:

Research institute.

Subjects:

Twelve adult Merino ewes (n= 6 per group).

Interventions:

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.

Measurements and Main Results:

Sepsis was characterized by hypotension (~ 12 mm Hg), increased heart rate (~ 80 beats/min), increased …