Production of cysteinyl-dopamine during intravenous dopamine therapy

Background. Oxidized dopamine rapidly forms thiol-conjugates with -SH group s on cysteine, glutathione, and proteins. We used cysteinyl-dopamine produc tion as an index of thioester production during intravenous dopamine treatm ent of critically ill patients. Methods. Cysteinyl-dopamine and catecholamines were measured by high-perfor mance liquid chromatography with electrochemical detection. The production of cysteinyl-dopamine by purified human neutrophils was measured using dopa mine (1 mu mo/L) and cysteine (1 mmol/L) concentrations similar to those fo und during dopamine treatment. To examine the impact of endotoxic shock on cysteinyl-dopamine production, anesthetized rats were given dopamine (12 to 15 mug/kg/min intravenously) with or without endotoxin (50 mg/kg intraveno usly). Results. In vitro, neutrophils converted 26% of dopamine to cysteinyl-dopam ine (30 min at 37 degreesC). Activating neutrophils with zymogen increased dopamine consumption from 26 to 68%, but only 36% appeared as cysteinyl-dop amine. The remainder map have been oxidized to other cysteinyl derivatives. Endotoxin increased cysteinyl-dopamine in rat plasma fi om 2.5 nmol/L (ran ge <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 cerebrosp inal fluid. In the plasma of eight patients receiving dopamine (6 to 20 <mu >g/kg/min for 1 to 3 days), dopamine was 0.5 to 9.9 mu mol/L, and cysteinyl dopamine was 48 to 1660 nmol/L. Cysteinyl-dopamine was 4.3 to 22.6% of dopa mine and correlated with leukocyte count (r(2) = 0.388, P = 0.099). Conclusions. A significant fraction of exogenously administered dopamine re acts with - SH groups of cysteine and probably: also with -SH groups on pep tides and proteins. During brief dopamine treatment of endotoxic shock in r ats, neither dopamine nor cysteinyl-dopamine crossed the blood-brain barrie r.