Dopamine Contamination of Infused Tyramine

Abstract

Clinical assessments of autonomic function often include tyramine (TYR) infusion. After uptake of TYR by sympathetic nerves via the cell membrane norepinephrine (NE) transporter and translocation of axoplasmic TYR into vesicles, NE exits the vesicles. Some of the NE enters the extracellular fluid and occupies adrenoceptors on cardiovascular smooth muscle cells, increasing blood pressure. A small proportion reaches the circulation, so that plasma NE concentrations increase (1)(2)(3). Jacob et al. (4) reported an ∼50-fold mean increase in plasma dopamine (DA) concentrations during intravenous TYR infusion, associated with “paradoxical” forearm vasodilation. We also noted high plasma DA concentrations in healthy volunteers during TYR infusion (5). When we assayed the catechol contents of the TYR infusate dispensed by our pharmacy [1 g/L (6.5 mmol/L)], we found that the infusate contained ∼50 μmol/L DA, corresponding to 0.7% contamination (6). Whether during TYR infusion such contamination could actually raise plasma DA concentrations was unclear, as was whether, while stored as is customary in solution at 4 °C, TYR could be converted to DA. The present study examined these possibilities. Solutions of TYR for infusion were prepared by the NIH Pharmaceutical Development Service, using TYR hydrochloride (Sigma) dissolved in sterile water, with pH ∼9. The solutions were stored either in a refrigerator at 4 °C or in an ultra-low temperature freezer at −70 °C for up to 9 months and then were assayed for catechol content, including DA. Infusate and arterial plasma concentrations of catechols were assayed (7), and hemodynamics were assessed before and during intravenous TYR infusion [6.5 μmol (1 mg)/min] in a total of 34 adults who underwent TYR infusion as part of autonomic function testing. Of the 34 participants, 6 were healthy volunteers, 13 were patients with chronic orthostatic intolerance, 9 had neurogenic orthostatic hypotension, 5 had …