Renal Extraction and Excretion of Mercury in Man Following Intravenously Administered Mercurial Diuretics 1

Abstract

Previous studies (1) from this laboratory have indicated that urinary excretion of mercury reaches a maximal value immediately following the intravenous injection of an organic mercurial diuretic and then falls rapidly, presumably as the plasma concentration of mercury decreases. Moreover, the dynamics of mercury excretion during the first four to six hours in a given individual are quite constant on repeated measurement and are not significantly affected by certain factors which either enhance or inhibit diuresis.In the present study the mechanisms by which mercury is removed from the plasma and excreted in the urine and the relationship of this process to mercurial diuresis have been investigated in human subjects with the aid of simultaneous measurements of renal hemodynamics, urinary mercury and electrolyte excretion, and arterial and renal venous plasma mercury concentrations. MATERIALS AND METHODSOf the six patients in this group, four were presumably free from renal disease. One patient (S. F.) had only one (right) kidney; another (W. M.) was recovering from glomerulonephritis.All studies were carried out in the post-absorptive state. A multi-holed, soft rubber catheter was inserted in the urinary bladder. After placing an indwelling needle into the femoral artery under local anesthesia (metycaine), appropriate solutions for the measurement of inulin or mannitol and PAH clearances were infused into an arm vein. Then, under fluoroscopic control, a cardiac catheter was placed into the right renal vein and the location of the tip doubly checked by determining the renal PAH extraction, as previously described (2). Following three or four control urine collection periods, 2 ml. (80 mg. mercury) of a mercurial diuretic were injected intra-1 Supported in part by grants from the National Heart Institute, U. S. Public Health Service, Campbell Pharmaceutical Co., and the Martha M. Hall Foundation.2 Ei Lilly Research Fellow in Medicine.venously. To maintain a higher and better sustained plasma concentration of mercury, in three patients an additional 2 ml. of the mercurial were added to the inulin-PAH solution, which was infused at approximately 4 ml. per minute. Thiomerin, which has no theophylline component that might modify the excretion of mercury, was given to five of the patients while Mercuzanthin was given to the sixth. Previous studies (3) have established that the renal action of Thiomerin is qualitatively and quantitatively similar to that of other mercurial diuretics.Following the administration of the mercurial, periodic urine collections were continued at 15 to 20 minute intervals for the determination of renal clearances, and urinary electrolyte and mercury excretion. At appropriate intervals, simultaneous femoral arterial and renal venous blood samples were also collected for the determination of the renal extraction of inulin, PAH, and mercury. In one patient (W. M.), catheterization of the renal vein was not attempted.The determinations of inulin, mannitol, PAH and electrolytes were carried out by ...

PLASMA REGRESSION, DISTRIBUTION AND EXCRETION OF RADIOMERCURY IN RELATION TO DIURESIS FOLLOWING THE INTRAVENOUS ADMINISTRATION OF Hg203 LABELLED CHLORMERODRIN TO THE DOG 1

“…These experiments are very similar in design to those of Weston and his co-workers (20) in man and may be considered as basically confirming their findings. One of the experiments, in which the animal was unilaterally nephrectomized immediately preceding the experiment, is summarized in Table III Table III and Figure 7 that mercury was much more rapidly extracted from the plasma than excreted during the interval immediately following injection of Chlormerodrin, i.e., for the first 30 to 60 minutes.…”

“…One of the experiments, in which the animal was unilaterally nephrectomized immediately preceding the experiment, is summarized in Table III Table III and Figure 7 that mercury was much more rapidly extracted from the plasma than excreted during the interval immediately following injection of Chlormerodrin, i.e., for the first 30 to 60 minutes. Hence the quantity of mercury accumulated in the kidney increased rapidly, a finding in the dog much like that of Weston and his associates in man (20). From 60 to 120 minutes, extraction and accumulation tended to reach a plateau.…”

Distribution of Radiomercury Administered as Labelled Chlormerodrin (Neohydrin®) in the Kidneys of Rats and Dogs 1

“…Further studies have shown that following administration of such compounds to humans and to animals a higher concentration of mercury is found in the kidney than in the other tissues examined, (2,3) and it appears that renal binding precedes the onset of diuresis (4,5). A number of such investigations have been carried out with the use of diuretics labelled with Hge0' (2,3), and this isotope administered as HgCl2 has been found by radioautographic means in high concentration in the renal cortex of rats (6).…”

Studies on Structure Diuretic Activity Relationships of Organic Compounds of Mercury 1

“…Mercuhydring (6,7) and Neohydring (8,9) have been shown to disappear rapidly from the blood stream following intravenous administration and to accumulate in the renal cortex in high concentration. Both drugs are highly bound to plasma proteins, hence are sparingly filtered through the glomerular capillaries, yet both are rapidly eliminated in the urine.…”

“…From 10 to 70 per cent of the dose was excreted in the two hours and forty minutes after intravenous administration. The clearance 7 of mercury ranged from 7 to 45 cc. per minute.…”