In 1957, Armstrong, McMillan and Shaw demonstrated a metabolite of epinephrine (E) and norepinephrine (NE) in normal human urine (2, 3). This substance, 3-methoxy,4-hydroxymandelic acid (VMA, for vanillylmandelic acid), was excreted in abnormally large amounts in three patients with pheochromocytomas (3). Recent studies of sympathomimetic amine metabolism (Figure 1) (4-7) suggested that the urinary excretion of the degradation products of E and NE, such as their 3-methylated derivatives (M and NM respectively) and VMA, might exceed E and NE excretion by some 10-or 20-fold. The diagnosis of pheochromocytoma might therefore be facilitated by analysis of urine for these phenolic compounds.Armstrong, Shaw and Wall's chromatographic technique for determination of urinary VMA (8, 9) was modified and used for the quantitative determination of VMA excretion in the urines of OH
Although numerous clinical studies have centered about the infusion of epinephrine and norepinephrine (1-3), the plasma concentrations attained by the infused catecholamines during such investigations have never been delineated. Recently a highly specific and sensitive procedure for the simultaneous fluorometric determination of epinephrine and norepinephrine in plasma was described (4, 5 while they were lying on a bed. Blood pressure and pulse were noted at various intervals. Routinely, 30 ml. blood specimens were drawn from the right antecubital vein into syringes wetted with heparin solution (sterile Liquaemin® Sodium, Organon Inc., Orange, N. J.), and then transferred immediately to cold 40 ml. centrifuge tubes equipped with ground glass stoppers. Specimens were chilled in an ice-water bath until the complete set for the particular experiment had been collected. They were then centrifuged at 700 G for 15 minutes following which the supernatant plasmas were removed and analyzed for epinephrine and norepinephrine as described elsewhere (4, 5). The plasma concentrations of catecholamine reported in this communication are uncorrected for recoveries which had been demonstrated previously to range from 70 to 90 per cent (5).Infusions were automatically terminated after infusion speeds of 30 ,ug. catecholamine per minute had been reached, or if a pulse pressure of 100 mm. Hg or a basal pressure increase of 100 mm. Hg were attained. Cessation of infusions also followed upon request of the subject, report of a persistent headache, or if the subject appeared extremely uncomfortable although willing to continue. RESULTSConstant rate infusions of epinephrine or norepinephrine were characterized by the attainment of steady state plasma concentrations as demonstrated in Figure 1. Although at times fluctuations in the steady state concentrations were observed, particularly for norepinephrine (cf. Curves B, C and E), the data in general were indicative of the maintenance of a dynamic balance between the rate at which the particular catecholamine was added to plasma and the rate at which it was simultaneously removed. Steady states were maintained for up to 65 minutes, the longest period tested. For epinephrine infusions, steady 1935
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