Orvis, Alan L.

The rates of disappearance D2O, Na22/24 and K42 from the arterial blood were determined in 17 dogs following rapid injection of the isotopes into the femoral and portal veins. Differences between systemic and portal venous injections were significant during the early phases of the disappearance of the isotopes (P < 0.05). Systemic insorption was simulated by continuous intravenous injection of D2O, Na22, and K42 at known rates into the femoral vein. The appearance of the isotopes in the arterial blood was determined repeatedly during and after their injection. The rate of injection (simulated insorption) was calculated using the mean systemic arterial disappearance rate. The differences between the calculated and actual rates of injection were insignificant. When portal insorption was simulated by constant injection of the isotope into the portal vein, the calculated rate of injection was not significantly different from the actual rate if the mean portal arterial disappearance curve was used in the calculation. When the systemic arterial disappearance curve was utilized, the calculated rate of injection was slightly faster than the actual rate. Submitted on July 11, 1962

The rates of movement of isotopically labeled water, sodium and potassium from the contents of segments of duodenum and ileum into the blood (insorption) and from blood to the contents (exsorption) were determined in dogs. The insorption of labeled water and sodium from the duodenal and ileal segments was exponential in character. Calculation of insorption and exsorption using the exponential rate and the Visscher formulation gave similar values. Anesthesia produced by pentobarbital sodium had no effect on the insorption of water and sodium from the intestinal segments, but it caused a small decrease in exsorption into the duodenum. Acidification of the contents of the intestinal segments decreased insorption of water, sodium and potassium, whereas it increased the exsorption of sodium and potassium without altering that of water. The results indicate that the mucosa of the duodenum fulfills the function of equilibrating its contents by maintaining nearly equal and large movements of water and sodium in both directions, while that of the ileum is fixed to serve absorption (a net gain to the body) of water and sodium.

Radioiodinated Hippuran was injected into the inferior vena cava of three unilaterally and three bilaterally nephrectomized dogs. Radioactivity was recorded over the precordium and remaining kidney in the former group and the precordium and renal fossa in the latter. The disappearance of I131 from plasma was analyzed and interpreted by two-compartment and three-compartment systems. Theoretical curves for cardiac and renal areas (constructed from analysis of arterial plasma samples) agreed well with curves from in vivo counting. Analyzed by either model, the first compartment exceeded the plasma volume severalfold, part seeming to be in the kidney. Extravascular compartments, impossible to sample, were not identified. About 15% of whole-blood radioactivity was in erythrocytes. Biliary excretion of Hippuran I131 was insignificant unless nephrectomy was bilateral; then up to 60% was excreted in the bile in 24 hr. Protein binding could not be demonstrated. Radiorenograms converted to fairly accurate rate constants may prove more useful than descriptive methods currently employed. Understanding the distribution and excretion of Hippuran appears helpful to accurate interpretation of the radiorenogram.

The total amount of I131-containing compounds excreted in the urine of the dehepatized dog receiving either radioactive thyroxine or triiodothyronine is similar to that of the normal dog receiving similar injections. The important role of the liver in the deiodination of thyroxine and triiodothyronine is indicated by the failure of the liverless animal to convert these compounds to inorganic iodide as completely as does the normal dog. Only a small percentage of the I131 compounds excreted by the liverless dog appears as inorganic iodide. The most abundant iodine compound in the urine of the dehepatized dog is a conjugate of thyroxine when thyroxine is injected, and an unidentified compound, b, when triiodothyronine is injected.

A study was made of the disappearance of sodium diatrizoate-I131 from the plasma of ten dogs after single intravenous injections. The plasma disappearance curves suggested a two-compartment system. The renal plasma clearance of diatrizoate-I131 calculated from these curves and the conventional renal plasma clearance of creatinine were not statistically different. Clearances calculated from the urinary excretion and midperiod plasma concentration of radioactivity in four experiments yielded values averaging 10% less than the creatinine clearance. Chromatographic studies of commercially available diatrizoate-I131 revealed the presence of about 5% free iodide and of about 5% of unidentified impurities. These impurities seem to account, partly at least, for the differences found between diatrizoate clearance and creatinine clearance. Biliary excretion and erythrocytic uptake of diatrizoate were minimal and did not appear to influence the analysis.

Forty-two male and female mice, 8 weeks old, were given radioiron (Fe59) in doses of 0.006–0.1 µc, containing 0.013–0.17 µg of iron, by intraperitoneal or intravenous routes. Assays of the radioactivity of the whole body revealed an initial rapid loss of Fe59 (15–20%) lasting about 6 days. Thereafter the Fe59 left the mice at a steady rate of 0.39%/day (half-life 180 days). One 34-year-old normal man was given 10.6 µc of Fe59, containing 8.2 µg of iron, intravenously. Based on counts from the entire body, the biologic rate of loss of the Fe59 was about 0.14%/day (half-life 500 days), and there was little or no initial loss such as occurred in the mouse. The Fe59 in the circulating erythrocytes was essentially unchanged for the first 3 months. It then fell to a new level of about 90% of the previous one; the mid-point of the fall was about 120 days after the administration of the radioiron. The difference in the rates of loss of radioiron from mice and man seems to be related primarily to the life span of the circulating red cells.

A study has been made at the Mayo Clinic of the results of treatment in 28 hypertensive patients receiving thiazide diuretics. The use of these agents produced a significant but very temporary reduction in plasma volume in most patients. The plasma volume reverted to or toward normal after the first week of treatment; therefore, hypovolemia could not explain the prolonged hypotensive effect of these drugs. Administration of thiazide diuretics did not deplete the body of its sodium stores, as measured by isotope studies in five patients on an unrestricted diet. Therapy with thiazides did not produce a persistent increase in urinary aldosterone excretion in the nine patients studied for this possibility.