Dobutamine does not influence inflammatory pathways during human endotoxemia

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 mu g.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-et, interleukins-6, -8, and -10) and secretory phospholipase A(2), 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 1, and plasmin-alpha 2-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.