Production of cysteinyl-dopamine during intravenous dopamine therapy

Abstract

Background. Oxidized dopamine rapidly forms thiol-conjugates with -SH groups on cysteine, glutathione, and proteins. We used cysteinyl-dopamine production as an index of thioester production during intravenous dopamine treatment of critically ill patients. Methods. Cysteinyl-dopamine and catecholamines were measured by high-performance liquid chromatography with electrochemical detection. The production of cysteinyl-dopamine by purified human neutrophils was measured using dopamine (1 μmol/L) and cysteine (1 mmol/L) concentrations similar to those found during dopamine treatment. To examine the impact of endotoxic shock on cysteinyl-dopamine production, anesthetized rats were given dopamine (12 to 15 μg/kg/min intravenously) with or without endotoxin (50 mg/kg intravenously). Results. In vitro, neutrophils converted 26% of dopamine to cysteinyl-dopamine (30 min at 37°C). Activating neutrophils with zymogen increased dopamine consumption from 26 to 68%, but only 36% appeared as cysteinyl-dopamine. The remainder may have been oxidized to other cysteinyl derivatives. Endotoxin increased cysteinyl-dopamine in rat plasma from 2.5 nmol/L (range <0.2 to 11) to 9.7 nmol/L (range <0.3 to 31, P = 0.1). After four hours, with or without endotoxin, cysteinyl-dopamine was <0.3 nmol/L in cerebrospinal fluid. In the plasma of eight patients receiving dopamine (6 to 20 μg/kg/min for 1 to 3 days), dopamine was 0.5 to 9.9 μmol/L, and cysteinyl-dopamine was 48 to 1660 nmol/L. Cysteinyl-dopamine was 4.3 to 22.6% of dopamine and correlated with leukocyte count (r2 = 0.388, P = 0.099). Conclusions. A significant fraction of exogenously administered dopamine reacts with -SH groups of cysteine and probably also with -SH groups on peptides and proteins. During brief dopamine treatment of endotoxic shock in rats, neither dopamine nor cysteinyl-dopamine crossed the blood-brain barrier.