Gerald P. Murphy

65Zn and 69mZn studies in the dog, monkey, and man: Prostatic scintiscanning

Abstract 65 Zn chloride and 69m Zn chloride and citrate have been studied in a total of 34 dogs, 2 rhesus monkeys, and 10 men. Timed concentrations were measured in the blood of all and in the bile, urine, and fresh tissues of 32 dogs and 2 monkeys. In addition, the influence of castration, timing, testosterone proprionate treatment, pilocarpine administration, and other combinations of these factors were studied. We have shown that significant prostatic concentrations of radioactive zinc were obtainable in the dog, in the monkey, and in man. In vitro scans of the dog prostate were obtained using 65 Zn chloride. Both in vivo and in vitro, clinical human prostatic scans were performed using 69m Zn chloride.

Erythropoietic responses to acute and chronic ureteral occlusions in dogs

Abstract Arterial and renal vein plasmas obtained from 58 nonanemic, nonuremic dogs subjected to unilateral ureteral occlusions acutely or for a period up to 5 weeks were assayed for ESF in the plethoric mouse. Despite the wide range of renal blood flows, resistances, and pO 2 levels, detectable elevations of ESF were not frequently observed. Complete or incomplete ureteral occlusions, infusion of vasoconstrictive agents, or the absence of the contralateral intact kidneys did not influence the ESF values. Elevation of arterial and renal vein ESF levels occurred only in animals subjected to acute ureteral occlusions at the level of the renal pelvis. These findings are discussed in the light of recent evidence for extrarenal control and release of ESF.

Functional characterization of isolated bloodless perfusion in baboon kidneys with oxygen and helium gases.

Abstract A method for isolated bloodless perfusion of primate (baboon) kidneys is described. Kidneys were perfused using oxygen or helium gas and the results compared. Improved renal cortical circulation with increase in the extractions of PAH and creatinine and filtration fractions was shown to be secondary to a generalized renal vasodilatation associated with helium exposure. In both gas systems renal autoregulation was present. A relative renal cortical vasoconstriction, as shown by similar measurements, was noted in the oxygen-treated kidneys. Salt and water concentration was maintained in helium-exposed kidneys despite little or no renal oxygen consumption, demonstrating that the isolated bloodless perfused kidney obtained adequate metabolic substrate from intrinsic or extrinsic stores provided in the perfusion system. Urinary enzymatic and electrolyte concentrations were normal with both gases and correlated with the observed renal morphological microscopic status. These and other observations on PAH transport and kinetics confirm that with the present perfusion system helium gas may be employed with benefit to the renal cortical circulation and metabolism.

Erythropoietin Release in Baboons after Renal Allotransplantation

Summary The level of plasma erythropoietin (ESF) from untreated baboon renal allotransplants, compatibly or incompatibly matched in terms of their major human ABO blood groups, was assayed in polycythemic mice. Postoperative rises in ESF occur within 7 days if graft thrombosis ensues. Other grafts exhibit progressive elevations in ESF activity, which correlate directly with the reduction in measured renal blood flow due to renal rejection. Azotemia does not evidently influence this response in this species. Compatibly matched animals demonstrate continued ESF responses despite restoration of peripheral hematocrit values to preoperative ranges.

Evaluation of pharmacologically induced renal vasodilatation

Summary In 47 experiments on anesthetized dogs the renal effects of the following vasodilatory agents have been determined: acetylcholine, isopropylarterenol, bradykinin, kallidin, tetraethylammonium chloride (TEAC) and hexamethonium chloride. The results were compared under test conditions utilizing both direct renal arterial and systemic intravenous infusions. Vasoactive peptides such as kallidin and bradykinin and other agents such as acetylcholine and isopropylarterenol exerted transient increases in renal blood flow and decreases in renal resistance. When given systemically the specific renal effects were often secondarily obliterated. Differences among these drugs in alteration of urine flow rate, renal vein pO2 and renal venous pressure were compared and their physiological basis defined under the limits of the experimental setting. Renal hemodynamic alterations were produced during renal vasodilatation with two ganglionic blocking agents: TEAC and hexamethonium. Renal vasodilatation produced by systemic TEAC did not reduce renal blood flow in contrast to hexamethonium. Both agents reduced renal resistance longer than the other compounds employed. TEAC produced small increases in renal venous pO2 even in the absence of increased blood flow. Hexamethonium exerted a more pronounced augmentative renal hemodynamic effect when given into the renal artery and produced a greater fall in blood pressure by both routes.

65Zn and 69mZn studies in the dog, monkey, and man

Abstract 65 Zn chloride and 69m Zn chloride and citrate have been studied in a total of 34 dogs, 2 rhesus monkeys, and 10 men. Timed concentrations were measured in the blood of all and in the bile, urine, and fresh tissues of 32 dogs and 2 monkeys. In addition, the influence of castration, timing, testosterone proprionate treatment, pilocarpine administration, and other combinations of these factors were studied. We have shown that significant prostatic concentrations of radioactive zinc were obtainable in the dog, in the monkey, and in man. In vitro scans of the dog prostate were obtained using 65 Zn chloride. Both in vivo and in vitro, clinical human prostatic scans were performed using 69m Zn chloride.

INTESTINAL AND PERITONEAL ABSORPTION OF RADIOIODINATED CHOLOGRAFIN AND RENOGRAFIN AS AN EXPERIMENTAL TEST OF GASTROINTESTINAL PERFORATION.

During radiographic gastrointestinal examinations with water-soluble diatrizoate compounds (1–5), several investigators (1–3) have observed radiopaque substances in the urinary tract when gastrointestinal perforation was demonstrated. Since it is known that the water-soluble compounds are rapidly eliminated from the blood stream by renal excretion (6), these observations were interpreted as indicating that in the presence of intestinal perforation, significant absorption into the blood stream via the peritoneum occurs. The normal adult intestinal tract rarely absorbs significant amounts of diatrizoates (2, 7). From the previous studies, it seemed that a clinical test for intestinal perforation could be devised from these findings. The authors therefore performed a series of experiments to test the validity of the clinical evaluations and, further, to determine the absorption and distribution of radioisotope-tagged diatrizoate methyl glucarnine (Renografin I125) and iodipamide sodium (Cholografin I131) fro...

Erythropoietin alterations in renoprival and renal allografted patients.

Summary and Conclusions Erythropoietin (ESF) is a hormone active in the regulation of RBC formation. It was commonly thought to originate only in the kidney and is believed to be activated or produced in the kidney in response to hypoxia. Three of 4 human renal allograft patients described here demonstrate that significant ESF activity occurs in the renoprival state. This observation in humans is consistent with previous experimental findings that an extrarenal source or sources of ESF do exist, and that humoral regulation of erythropoiesis persists in anephric man and animals. The validity of ESF detection as a prognostic indicator of graft viability and function is discussed.

The effects of ethacrynic acid diuresis on renal hemodynamics and Hg203 chlormerodrin excretion

Abstract The renal functional effects of ethacrynic acid in varying doses have been tested in the dog during normotension, hemorrhagic hypotension, and renal artery stenosis. A transient increase has been observed in renal blood flow at the largest dose given. Alterations were produced in the intrarenal concentration and the urinary excretion of Hg 203 chlormerodrin by changing the dosage and route of administration of ethacrynic acid. This has been discussed in the light of the present knowledge of the renal tubular activity of specific organic mercurials and of ethacrynic acid.

Radioisotope studies in isolated perfused baboon kidneys

Abstract Radioisotopic studies were performed on baboon kidneys during isolated bloodless perfusion. The perfusion was equilibrated with either 100% oxygen or 100% helium gas. The clearance of 133 Xe was found to be a very sensitive method in assessing renal circulation. Oxygen had a vasoconstrictive effect on the cortical vessels resulting in a decreased renal cortical perfusion flow. The distribution of labeled carbon microspheres did not reflect a difference in cortical flow during oxygen and helium exposure. Particles of the size employed did not remain fixed in the vascular tree. In some instances free or unbound isotope was detected. 203 Hg chlormerodrin was poorly concentrated both during oxygen and helium exposure, presumably as a result of the absence of plasma proteins in the perfusate. Helium-exposed kidneys showed a more normal distribution and excretion of 131 I hippuran than oxygen-exposed kidneys.