Dobutamine does not influence inflammatory pathways during human endotoxemia*

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Abstract

Objective:

Catecholamines have anti-inflammatory and anticoagulant properties. Dobutamine is a synthetic catecholamine frequently used in patients with septic myocardial dysfunction. The objective was to determine whether a continuous infusion of dobutamine exerts immunomodulatory effects in healthy volunteers challenged with endotoxin.

Design:

Prospective, open-label study.

Setting:

Clinical research unit of a university hospital.

Participants:

Sixteen male healthy volunteers.

Interventions:

Volunteers received a constant infusion with dobutamine (10 μg·kg−1·min−1, n = 8) or physiologic saline (n = 8). All participants were challenged with a bolus injection of endotoxin prepared from Escherichia coli (4 ng/kg). Dobutamine infusion was commenced 1 hr before endotoxin challenge and was continued until 3 hrs thereafter.

Measurements and Main Results:

Dobutamine infusion was associated with an increase in mean arterial blood pressure (peak 122 ± 5 mm Hg) and heart rate (peak 84 ± 4 beats/min, both p < .05 vs. saline). Endotoxin injection induced the systemic release of cytokines (tumor necrosis factor-α, interleukins-6, -8, and -10) and secretory phospholipase A2, endothelial cell activation (increase in the plasma levels of soluble E-selectin and von Willebrand factor), activation of coagulation (increased plasma levels of soluble tissue factor, F1 + 2 prothrombin fragment, and thrombin-antithrombin complexes), and activation with subsequent inhibition of fibrinolysis (increased plasma concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor type I, and plasmin-α2-antiplasmin complexes). None of these responses were influenced by dobutamine.

Conclusions:

Dobutamine, infused in a clinically relevant dose, does not influence inflammatory and coagulant pathways during human endotoxemia.

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